Management of Kidney Diseases 2023

Management
of Kidney
Diseases
Debasish Banerjee
Vivekanand Jha
Nicholas M. P. Annear
Editors
123
Management of Kidney Diseases
AL GRAWANY
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Debasish Banerjee • Vivekanand Jha
Editors
Management of Kidney
Diseases
AL GRAWANY
Editors
Debasish Banerjee Vivekanand Jha
St George’s University Hospitals NHS The George Institute for Global Health
Foundation Trust and St George's, New Delhi, India
University of London
London, UK
St George’s University Hospitals NHS
Foundation Trust and St George’s,
University of London
London, UK
ISBN 978-3-031-09130-8 ISBN 978-3-031-09131-5 (eBook)

https://doi.org/10.1007/978-3-031-09131-5
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Switzerland AG 2023
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Foreword
There was a time, not that long ago, when nephrology was a speciality only
practiced in a few high-income countries. There was a time when available
nephrology experts were so few, and the cost of kidney replacement therapy so
high, that it seemed nephrology would never expand beyond those countries.
And there was little available evidence to guide the work of nephrologists, so
the world hung on the expert advice of those few from high-income countries.
Happily those times are gone. Nephrology is now a worldwide speciality,
recognising its unique clinical challenges in different parts of the world. True
experts and authoritative teachers in nephrology come from almost every part
of the world. There is a growing library of high-quality evidence to support
the clinical work of nephrologists everywhere.
This book reflects those changes. It covers the whole gamut of nephrology
in all parts of the world. Its editors and contributors come from many differ-
ent heritages and practice in many different places.
The book presents all aspects of modern nephrology, with a clear focus on
practical clinical management. And it is especially welcome that coverage
includes topics which in recent years are gaining in importance as their con-
tribution to the best nephrology care is being better understood. One such
theme is transitional care for adolescents and young adults. Another is a more
informed and balanced approach to the value of conservative care in the man-
agement of advanced kidney failure. Another is the increasing role of renal
registries informing practice, assisting service planning, and providing a sub-
strate for audit, research and clinical quality improvement.
The book provides the reader with a most approachable and clear knowl-
edge base—case-based discussions and concise text; multi-coloured dia-
grams, flow charts, and tables which are easily assimilated; key practice
points; the inclusion of current high-quality evidence; questions at the end of
each chapter to help readers test their assimilation of knowledge.
The three lead editors and their many and diverse contributors have pro-
duced a first-rate text that will be much read and well used around the world.
It will certainly be popular with specialist trainees equipping themselves for
future practice and preparing for the examinations required of most before
their training is completed. And it is a most handy reference for practice and
teaching which will also be used by established specialist nephrologists.
Oakham, UK John Feehally

October 2022
AL GRAWANY
Preface
Worldwide, practicing nephrologists often need rapid and easily accessible

information on evidence-based management for kidney patients, both in
hospital and outpatient clinic settings. Kidney disease is a growing public
health burden: patients with kidney disease have multiple associated health
conditions and need care from a diverse group of healthcare professionals.
The need for practical, evidence-based treatment recommendations for
patients with kidney disease in all healthcare settings, that is mindful of
available resources, has never been more evident than during the COVID-19
pandemic.
This book brings together the expertise of kidney health specialists from
all over the world to provide practical management guidance for all regions,
with variable healthcare resources and accessibility. The practice points inte-
grated into each chapter are useful short practical reminders in the steps of
management. Appropriate references, including recent guidelines, have been
cited. The authors have incorporated recent KDIGO and other national guide-
lines, where available and appropriate. We are enormously grateful to KDIGO
for endorsing the use of all available KDIGO guidelines and conference
updates in the book.
The case-based approach is oriented towards illustrating the clinical pic-
ture, explaining the current understanding of the pathophysiology and man-
agement, which we hope will help outline the ‘why’ and ‘how’ aspects of
routine patient care.
Updating knowledge in all aspects of kidney care can be daunting, not
only for practicing nephrologists but also for trainees before examinations.
The case-based, management focused, up-to-date approach to illustrating all
kidney conditions, including kidney replacement therapies, will also aid con-
textualisation and revision for end-of-training examinations.
Another unique feature of this book is Springer’s interactive flashcards,
with 270 practice questions, authored by our international experts, which will
help trainees—and fully trained nephrologists—consolidate their knowledge,
monitor progress and learn from the available explanations.
We wish to thank all of our expert international authors for their fantas-
tic work in putting together each chapter; to our publishing team, in par-
ticular Melissa Morton and Mahalakshmi Sathish Babu, for their tireless
support throughout the development of this book; to our colleagues and
vii
viii Preface
trainees for continuing to inspire and motivate us; and of course most of all
to our families for sacrificing the time, space and support to complete this
important project.
London, UK Debasish Banerjee

London, UK Nicholas M. P. Annear
New Delhi, India Vivekanand Jha
July 2022
AL GRAWANY
Contents
1 he Approach to the Patient with Kidney Disease�� 1

T
Debasish Banerjee, Nicholas M. P. Annear,
and Vivekanand Jha
2 I nvestigating Kidney Disease�� 11
Mukunthan Srikantharajah, Rukma Doshi, Debasish Banerjee,
Vivekanand Jha, and Nicholas M. P. Annear
3 roteinuria and Haematuria�� 35
P
David Makanjuola and Dwomoa Adu
4 cute Kidney Injury�� 51
A
Indre K. Semogas, Jill Vanmassenhove, Nishkantha
Arulkumaran, and Nicholas M. P. Annear
5 hronic Kidney Disease (CKD): Evaluation of the
C
Cause and Prevention of Progression�� 75
Debasish Banerjee and Arpita Roychowdhury
6 KD: Management and Prognosis�� 85
C
Adeera Levin and Magdalena Madero
7 anagement of Anaemia in Chronic Kidney Disease�� 93
M
Sunil Bhandari and Chuan-Ming Hao
8 lood Pressure in CKD�� 115
B
Lisa Crowley and Indranil Dasgupta
9 ineral and Bone Disorder in CKD�� 131
M
Miho Murashima and Takayuki Hamano
10 iabetes and CKD�� 147
D
Daniel Murphy, Vivekanand Jha, and Debasish Banerjee
11 ardiovascular Complications of CKD �� 167
C
Rebecca Shone, Charles A. Herzog, and Debasish Banerjee
12 rimary Glomerular Disease�� 199
P
Raja Ramachandran and Neil Sheerin
13 econdary Glomerular Disease and Renal Vasculitis �� 213
S
Neil Sheerin and Raja Ramachandran
ix
x Contents
14 I nfections and the Kidney �� 229

Saraladevi Naicker, John B. Eastwood, Gloria Ashuntantang,
and Ifeoma Ulasi
15 G
enetic Kidney Diseases�� 269
Radaa G. Sritharan, Jill Vanmassenhove, Anand K. Saggar,
J. Christopher Kingswood, and Nicholas M. P. Annear
16 Kidney Cancer�� 327
Rebecca Shone, Anna Walsh, Luke Stroman,
Christopher Anderson, and Nicholas M. P. Annear
17 H
emodialysis in Clinical Practice �� 349
Mohamed Elewa and Sandip Mitra
18 C
omplications of Haemodialysis�� 363
Oluwatoyin I. Ameh, Udeme E. Ekrikpo, Aminu K. Bello,
and Ikechi G. Okpechi
19 Peritoneal Dialysis�� 383
Angela Yee-Moon Wang
20 C
omplications of Peritoneal Dialysis:
Prevention and Management�� 405
Brett Cullis and Robert Freercks
21 K
idney Transplantation: The Pre-Transplantation
Recipient & Donor Work-Up�� 421
Pankaj Jawa, Prabir Roy-Chaudhury, and Roberto Ceratti
Manfro
22 M
anagement of the Patient After Kidney Transplantation�� 435
Madhu Bhaskaran and Shahrzad Ossareh
23 C
omplications of Kidney Transplantation�� 455
Mysore Phanish, Pranaw Kumar Jha, and Abbas Ghazanfar
24 A
n Approach to Obstetric Nephrology�� 489
Anita Banerjee, Serene Thain, and Brenda Sequeira Dmello
25 T
ransitional Care of Adolescents and Young Adult
Patients with Kidney Disease�� 505
Joyce Popoola and Christopher Esezobor
26 C
onservative Care for Patients with Chronic
Kidney Disease �� 521
Helen Alston and Katie Vinen
27 E
lectrolytes & Acid Base Disorders�� 539
Gates B. Colbert, Ajay Kher, Kareem Genena,
and Edgar V. Lerma
28 T
he Role of Renal Registries�� 563
Mogamat Razeen Davids, Fergus J. Caskey,
and John B. Eastwood
Index�� 575
AL GRAWANY
The Approach to the Patient
with Kidney Disease
1
Debasish Banerjee , Nicholas M. P. Annear ,
and Vivekanand Jha
Clinical Scenario ing 14.5 million people are estimated to require

A 40 year old female international traveller pres- kidney replacement therapy by 2030 [1, 2]. The
ents with a history of fever, dysuria and a serum initial approach to diagnosis of kidney disease,
creatinine of 208 μmol/L (2.35 mg/dL). She is and management of patients on kidney replace-
assessed as confused in the emergency department therapy requires a careful history, physical
ment, but has been found to be haemodynami- exam and initial laboratory tests, which are
cally stable, with a temperature of 37 °C (98.6 °F), emphasised in this chapter.
a blood pressure of 130/75 mmHg, and pulse of
70 beats per minute. She has indicated that she is
due to fly back home in 2 days’ time. ommon Kidney Patient
C
How would you proceed? Presentations
Kidney patients present may with symptoms,

Introduction signs and abnormal investigations, with a hitherto
unknown kidney disease. Careful history taking
Kidney disease is increasing in incidence world- and a full physical examination can help the cli-
wide, with increasing numbers of patients on kid- nician to arrive at a provisional diagnosis for the
ney replacement therapy; more kidney patients kidney condition - these include common kidney
are looked after by internists, general practitio- syndromes, such as nephrotic syndrome, nephritic
ners and other specialties than by nephrologists. syndrome, chronic kidney disease and acute kid-
Furthermore, kidney disease is now the 12th ney injury (Fig. 1.1). A tailored investigation
leading cause of death worldwide, and a stagger- with urinalysis, blood tests and imaging can help
to identify the cause of kidney disease, and for-
mulate a management plan.
D. Banerjee (*) · N. M. P. Annear Patients with known kidney disease, on kid-
St George’s University of London, London, UK ney replacement therapy may also present with
St George’s University Hospitals Foundation Trust, complications of chronic kidney disease, or com-
London, UK plications of their modality of kidney replace-
e-mail: dbanerje@sgul.ac.uk; nannear@sgul.ac.uk ment therapy. For example, haemodialysis
V. Jha patients may present to the emergency depart-
The George Institute for Global Health, ment with shortness of breath—particularly fol-
New Delhi, India lowing a prolonged interdialytic period, such as
e-mail: vjha@georgeinstitute.org.in
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 1

D. Banerjee et al. (eds.), Management of Kidney Diseases,
https://doi.org/10.1007/978-3-031-09131-5_1
2 D. Banerjee et al.
Pallor/greyish hue to Facial / periorbital

the skin oedema
Facial malar rash (SLE)

Raised or low jugular
venous pressure (JVP)
Guam hypertrophy (CYA /
Ca2+ channel blockers)
Hypo/Hypertension
Coarse crepitations
over lung bases
Tachycardia
Renal angle tenderness,

Decreased skin turgor Ballotable kidneys,
Nephrectomy scars
Suprapubic tenderness
/ palpable bladder
Macroscopic/microscopic
haematuria; frothy urine
vasculitic rash –
buttocks / lower
legs (IgAN/HSP)
Leg oedema
Also inspect groins, neck, precordium, and abdomen for scars/evidence suggestive of
current or previous kidney replacement therapy (haemodialysis (arteriovenous
fistula/dialysis catheter) /peritoneal dialysis (tenchkoff catheter) access and/or
transplantation (J-shaped/Rutherford-Morrison scar)).
SLE – systemic lupus erythematosus; CYA – cyclosporin; Ca2+ channel blockers –

Calcium channel blockers; IgAN – IgA nephropathy; HSP – Henoch Schonlein Purpura
Fig. 1.1 Physical signs that can be associated with kidney disease
after the weekend; peritoneal dialysis patients treatment if necessary. Kidney replacement ther-
and kidney transplant patients may present with apy is available in all countries; and patients are
fever and abdominal pain, both requiring careful frequently managed by clinicians other than
history and physical examination to arrive at a nephrologists, hence a good working knowledge
likely differential diagnosis, and start immediate about how to make a prompt diagnosis, and man-
AL GRAWANY
1 The Approach to the Patient with Kidney Disease 3
Table 1.1 The approach to the kidney patient depends on Acute kidney injury: A sudden rise in serum cre-
the presence of a past history of kidney replacement
atinine over hours or days (>50% from baseline).
therapy
Chronic kidney disease: Gradual, progressive
Patients with no known Patients on dialysis, with
kidney disease kidney transplantation
and irreversible rise in serum creatinine over at
Presents with symptoms or Presentation with least 3 months.
signs such as oedema, general signs and Kidney stones: Colicky loin pain, haematuria
oliguria suggestive of kidney symptoms such as with graveluria.
disease or urine breathlessness, fever or Urinary tract obstruction: Inability to pass
abnormalities and rising chest/abdominal pain in
creatinine patients on kidney urine, with structural and functional abnormali-
replacement therapy ties with urinary retention.
Requires a careful history Requires a careful Kidney tubule defects: Abnormalities of elec-
and physical examination to history and physical trolytes, acid-base in blood and urine.
formulate a differential examination to
diagnosis from common formulate a differential
Urinary tract infections: Infections of kidney,
kidney syndromes such as diagnosis for causes of ureter, urinary bladder, prostate or urethra.
nephrotic syndrome, breathlessness, fever and
nephritic syndrome, chronic chest/abdominal pain
kidney disease or acute
kidney injury
natomical Localisation of Kidney
A
Diseases
age complications is important amongst nephrol- The presenting signs, and symptoms, and pres-
ogists and non-nephrologists alike, in all regions ence of blood and urinary abnormalities are
of the world (Table 1.1). dependent on the anatomical structure of the uri-
nary tract involved, as shown in the Table 1.2.
ommon Kidney Syndromes

C Table 1.2 Clinical features of kidney diseases, as deter-
mined by anatomical involvement of the urinary organs
and Definitions
Anatomical
structure Clinical features of presentation
Haematuria: Abnormal number of red blood cells
Kidneys Loin pain, hematuria, frothy urine, renal
(RBCs) in the urine, either visible or detected on angle tenderness, oliguria, polyuria,
urine examination, >3 RBCs/high power field nocturia, raised creatinine, electrolyte
under the microscope. abnormalities
Nephrotic syndrome: Significant proteinuria Ureters Loin to groin pain, colicky in nature,
haematuria, graveluria
(>3 g/day), with oedema, hypoalbuminaemia,
Urinary Lower abdominal pain, dysuria,
hypercholesterolaemia, and a hypercoagulable state. bladder hematuria, suprapubic tenderness,
Nephritic syndrome: Glomerular haematuria leukocyturia
with proteinuria, dysmorphic RBCs, red cell casts, Urethra Dysuria, hematuria at the initiation of
often a raised serum creatinine, and hypertension. micturition
Aetiology of Kidney Syndromes aetiologies may present with acute or chronic

kidney diseases, the understanding of which
Understanding the common causes of kidney helps with determining the reversibility of the
syndromes can help to inform the approach pathological process and urgency of treatment
to diagnosis and management. Some of the (Table 1.3).
Table 1.3 Common causes of kidney syndromes

Kidney syndrome Site affected Causes
Haematuria Kidney Inflammation, infection, cancer, stone
Kidney outflow tract Stone, cancer, infection, inflammation
Nephrotic Kidney limited (or Minimal change, membranous, focal segmental glomerulosclerosis
syndrome idiopathic) (FSGS)
Systemic (or secondary) Diabetes, mellitus lupus, Amyloidosis, Cancer: Lymphoma,
Myeloma, Drugs: Gold, Antibiotics, NSAIDS, Heroin,
Penicillamine, Infections: HIV, Hepatitis B, Hepatitis C, Malaria,
Syphilis, Alport’s syndrome, Nail-Patella syndrome
Nephritic Kidney limited (or IgA nephropathy, kidney limited vasculitis
syndrome idiopathic)
Systemic (or secondary) Lupus, ANCA-associated vasculitis (AAV)
Kidney stones Calcium oxalate, urate, struvite, cysteine
Urinary tract Ureter Stones, cancer
obstruction Urethra/ bladder outflow Stones, prostate cancer
Kidney tubular Acidosis Renal tubular acidosis
disorder
Urinary tract Bacterial Escherichia coli, Klebsiella pneumoniae
infection (UTI) Fungal Candida albicans
Viral Cytomegalovirus (CMV), BK virus, adenovirus
Acute kidney Pre-renal Volume depletion, haemorrhage
injury Renal Acute interstitial nephritis (AIN), Acute Glomerulonephritis
Post-renal Urethral/bladder outflow obstruction
Chronic kidney Diabetes mellitus, Hypertension, chronic glomerulonephritis,
disease inherited kidney diseases
AL GRAWANY
pproach to a Patient with Kidney

A chronic kidney disease (CKD) over months. The
Disease presence of fever, skin rash and joint pains indi-
cates systemic disease. Visible haematuria indi-
A careful history and physical exam is necessary cates glomerular or renal tract bleeding. The
to identify the kidney syndrome and identify the presence of oedema may be associated with
cause. The duration of illness is important to nephrotic syndrome, fluid retention or end stage
determine the syndrome: for example, acute kid- kidney disease (ESKD). The physical is followed
ney injury (AKI) develops in hours to days, and by tests of blood and urine (Tables 1.4 and 1.5).
Table 1.4 Approach to common kidney syndromes

Kidney
syndrome History Physical examination Investigations
Haematuria Age of onset (malignancy Hypertension, oedema, Urine microscopy for RBCs,
if>50 years), gender (bladder abdominal mass, palpable dysmorphic RBCs, RBC casts,
cancer and prostate cancer is bladder urinalysis for blood, leucocytes
commoner in males, infection & nitrites (infection),
in females), associated proteinuria, test for myoglobin.
symptoms: Fever, dysuria, flank Ultrasound, computerised
pain, family history (Alport’s), tomography (CT), cystoscopy
travel history (schistosomiasis),
smoking, anticoagulation,
pharyngitis (IgA nephropathy)
Nephrotic Peripheral and facial oedema, Dependent oedema, malar rash, Urine protein, albumin, cells,
syndrome frothy urine. History of diabetes scarring alopecia, telangiectasia, casts, lipids, urinary bence
(and mellitus, diabetic retinopathy. erythema nodosum, jaundice, jones protein (BJP). Serum
non-nephrotic Fever, iv drug use, high risk spider naevi, leukonychia, creatinine, liver function, full
proteinuria) sexual behaviour, malaria, yellow nails, dystrophic nails blood count. ANA, ANCA,
filaria; drugs NSAIDS, gold, anti-GBM, complement* (Table
penicillamine 1.5), ASOT, cryoglobulins,
hepatitis B, C & HIV serology,
ultrasound, kidney biopsy
Nephritic Dark brown, tea-coloured or Hypertension, oedema, hearing Urine microscopy: dysmorphic
syndrome smoky urine, sore throat (IgA impairment (Alport’s RBC, casts, proteinuria >0.5 g/
nephropathy) respiratory, skin syndrome), skin lesion (Lupus, day, full blood count, serum
infections (post-streptococcal), henoch-schonlein purpura creatinine, liver profile, ANA,
family history (Alport’s (HSP), vasculitis, Fabry’s ANCA, anti-GBM,
syndrome), fever, skin rash, disease) complement*, ASOT,
joint pain (lupus nephritis), cryoglobulins, hepatitis B, C &
haemoptysis (vasculitis) HIV serology, ultrasound,
kidney biopsy
Kidney stones Haematuria, loin to groin pain, Fever, costo-vertebral ‘renal Full blood count, serum
nausea, vomiting. High oxalate, angle’ tenderness calcium, phosphate, urate, pH
high protein, high salt diet. Urinary RBC, WBC, pH,
Drugs triamterene, crystals. 24 h urine calcium,
sulphonamides, indinavir. urate, citrate, oxalate, sodium
Hyperparathyroidism, Non-contrast helical CT of the
sarcoidosis, bile salt depletion, kidneys, ureters and bladder
short gut. Reduced fluid, (KUB), renal tract ultrasound
excessive sweat
Urinary tract Flank pain, suprapubic pain, Enlarged urinary bladder, Urine RBC, WBC, raised serum
obstruction suprapubic fullness. Urine enlarged prostate, uterine creatinine, hyperkalaemia,
frequency and urgency (partial prolapse acidosis, renal tract ultrasound
obstruction). Anuria (urethral). and CT scan
Haematuria (stones, cancer)
suprapubic fullness, frequency
nocturia
(continued)
Table 1.4 (continued)

Kidney
syndrome History Physical examination Investigations
Kidney Renal stones, short stature, Blood pH, electrolytes, urine
tubular family history electrolytes, pH
disorder
Urinary tract Urinary frequency and urgency, Suprapubic tenderness, flank Urinalysis for blood, leucocytes
infection dysuria, cloudy urine, smelly pain/renal angle tenderness, & nitrites (infection), MSU
(UTI) urine, fever, flank pain signs of sepsis (fever, culture to isolate causative
tachycardia, hypotension) organisms, FBC, blood urea,
serum creatinine, electrolytes,
CRP and blood culture if
immune suppressed or signs of
systemic sepsis.
Ultrasound ± CT scan if
obstruction or stones suspected,
recurrent, or failure to resolve
with first line therapy
Acute kidney History of salt and water loss, Blood pressure & pulse, Blood urea, serum creatinine,
injury drug history, fever, history of postural drop on assessing electrolytes. Urinary sodium,
CKD, rash, hair loss, joint pain lying/standing blood pressure, creatinine, osmolality, blood,
dry mucus membranes, rash, protein, microscopy, RBC,
alopecia, jaundice, ulcers, casts, eosinophil
palpable bladder Ultrasound of the renal tract,
kidney biopsy
Chronic History of hypertension, Blood pressure, pulse lying/ Full blood count, serum
kidney disease diabetes, AKI, lupus, hepatitis, standing, oedema, wasting, creatinine, electrolytes, calcium,
scleroderma, vasculitis, familial retinal exam, palpable kidney, phosphate, liver function, lipids.
CKD. Polyuria, nocturia, urinary bladder Urine protein, ultrasound of the
haematuria, proteinuria. renal tract
Anorexia, nausea vomiting
Table 1.5 Conditions causing abnormalities in comple- further history taking, physical examination and
ment levels tests to establish a diagnosis.
Complement
levels Condition
Low C3, Low Lupus nephritis Haematuria
C4 Cryoglobulinaemia
Infective endocarditis
Shunt nephritis Haematuria is defined as an abnormal number of
Type 1 mesangio-proliferative red cells in the urine i.e. more than 3 red blood
glomerulonephritis (MPGN)
cells seen under one high power field under the
Low C3, Type 2 mesangio-proliferative
Normal C4 glomerulonephritis (MPGN) laboratory microscope. Haematuria may originate
Post-infective/post-streptococcal from the kidneys, or from the urinary tract.
glomerulonephritis Table 1.6 can help with differentiating between
the two:
Investigations for haematuria will be guided
Radiological Abnormalities by the presentation, but may include urine
microscopy, urinary protein quantification, ultra-
Radiological abnormalities of the urinary tract sound of the kidneys and urinary tract, and CT
may be picked up incidentally, and should prompt and cystoscopy if necessary (Tables 1.7 and 1.8).
AL GRAWANY
Table 1.6 Clinical features of haematuria from kidney Table 1.8 Causes of red or brown urine
compared to that from urinary outflow tract
Endogenous
Haematuria originating substances Foods Drugs
from the urinary Red blood cells Food colouring Rifampicin
Haematuria outflow tract: ureters,
Haemoglobin Beetroot Adriamycin
originating from urinary bladder &
the kidneys urethra
Myoglobin Blackberries, Chloroquine
Bilirubin Blueberries Deferoxamine
Age at Could be at any Usually >50 years
presentation age Porphyrins Fava beans Levodopa
Urine colour Dark red, brown, Bright red
Melanin Paprika Methyldopa
smoky Rhubarb Metronidazole
Urinary clots No Yes Nitrofurantoin
Mixed with urine Yes May be at beginning or Phenytoin
end of micturition Prochlorperazine
Lower urinary No Yes Quinine
tract symptoms Sulfonamides
Proteinuria Yes No
Dysmorphic red Yes No
blood cells
(RBCs)
resentation of Kidney Failure
P
Oedema Yes No
Raised serum Yes No
Patients on Kidney Replacement
creatinine Therapy
Hypertension Yes No
Fever, rash, chest Yes No
Common presenting features for kidney failure
symptoms
patients on kidney replacement therapy include,
fever, breathlessness, chest pain, confusion, fatigue,
Table 1.7 Common causes of haematuria falls and abnormal blood tests such as hyperkalae-
Category Cause
mia and rising serum creatinine in a kidney trans-
Benign Renal masses (angiomyolipoma (AML), plant patient. Infection and malfunction of dialysis
oncocytoma vascular access are very common causes of acute
Benign prostatic hypertrophy (BPH)
Urethral strictures
admissions for patients on haemodialysis and peri-
Stones Staghorn calculi toneal dialysis, followed by breathlessness due to
Calcium stones fluid volume overload. Rapid ultrafiltration on hae-
Uric acid stones
modialysis and obligatory ultrafiltration with peri-
Infective Pyelonephritis
Cystitis toneal dialysis can alternatively lead to volume
Urethritis depletion, hypotension and falls, particularly in
Trauma Pelvic trauma
Renal injuries
elderly dialysis patients. Fatigue and tiredness due
Foreign bodies to anaemia and malnutrition are also common com-
Renal IgA nephropathy plaints in patients on renal replacement therapy.
Thin basement membrane disease
Hereditary nephritis
A rising serum creatinine on routine blood test
Medullary sponge kidney results is a common reason for hospital atten-
Iatrogenic Recent endoscopic procedure (e.g. transurethral dance in kidney transplant recipients, which
resection of the prostate (TURP)
Transrectal ultrasound (TRUS) guided prostate
could be due to acute transplant rejection, urinary
biopsy infection, transplant urinary tract obstruction,
Traumatic catheterisation transplant renal artery stenosis, or most com-
Radiation
Indwelling ureteric stents monly volume depletion (Table 1.9).
Renal biopsy
Extracorporeal shockwave lithotripsy (ECSWL)
Malignant Renal cell carcinoma
Transitional cell carcinoma
Squamous cell carcinoma
Urothelial cell carcinoma
Prostate acinar adenocarcinoma
Table 1.9 Common causes to consider based on symptoms and blood results in patients on kidney replacement
therapy
Common
symptoms Haemodialysis Peritoneal dialysis Kidney transplantation
Fever Dialysis access related PD catheter exit site Urinary tract infection atypical
infection infection, peritonitis infection of chest and blood stream e.g.
Infections of chest and Infections of chest and CMV, EBV, TB
urine urine
Breathlessness Fluid overload Fluid overload Fluid overload
Chest infection Chest infection Chest infection
Anaemia, loss of native Anaemia, loss of native Anaemia
renal function renal function
Fatigue Anaemia Anaemia Anaemia
Malnutrition Malnutrition
Falls Hypotension due to excess Hypotension due to excess Volume depletion, infection
ultrafiltration on dialysis ultrafiltration on dialysis
Drug-induced hypotension Drug-induced hypotension
Cardiac arrythmias, Cardiac arrythmias,
infection infection
Hyperkalaemia Missed dialysis High potassium diet, Tacrolimus
High potassium diet underlying high cell High potassium diet
turnover state Kidney transplant failure
Conclusions tacrolimus and mycophenolate mofetil. Her most

recent serum creatinine level was 200 μmol/L
Returning to the clinical scenario from the begin- (2.26 mg/dL) 2 months ago, and she has a history
ning of the chapter, the differential diagnosis of recurrent transplant urinary tract infections,
with the available information is extremely most recently an Escherichia Coli, fully sensitive
broad, and includes an acute kidney injury, to standard antimicrobial agents.
chronic kidney disease, a new presentation with A full physical examination reveals—in addi-
glomerulonephritis, urinary tract infection, or an tion to the findings reported previously—a non-
infective complication of known end stage kid- functioning right radiocephalic arteriovenous
ney disease. Further clarification is only really fistula from previous haemodialysis, a right-sided
possible through eliciting a careful medical his- Rutherford-Morrison scar, overlying a non-
tory, and performing a thorough physical exami- tender mass. There is mild suprapubic tender-
nation, which will in turn determine the most ness. There was no peripheral oedema, but she
appropriate next investigations, and an appropri- had a mild resting tremor. Neither her white cell
ate, safe plan for management, including whether count nor CRP were raised; her tacrolimus trough
she is likely to be fit to fly home: level was 6 ng/mL, and her blood sugar was
The patient had been assessed as confused 5.6 mmol/L; Her urinalysis was positive for leu-
because she was having difficulty communicat- kocytes and nitrites, but was otherwise clear. A
ing with staff in the emergency department: transplant renal tract ultrasound revealed no evi-
thankfully, one of the hospital nursing team was dence of obstruction, a small post-micturition
able to speak with her coherently in her native bladder residual volume of 60 mL, and normal
language. She shows the assessing clinician a let- resistive indices (RIs) of 0.68.
ter from her nephrology team at home, which on A clinical diagnosis of kidney transplant uri-
translation, indicates that she has end stage kid- nary tract infection is made: given the absence of
ney disease due to IgA nephropathy, and was haemodynamic compromise, and a clear history of
transplanted with a deceased donor (donation similar presentations, with a serum creatinine at
after circulatory death (DCD)) kidney 5 years her baseline, and on agreement with both the local
ago, and is chronically immune suppressed with nephrology, and her home nephrology teams, it
AL GRAWANY
was deemed appropriate to manage her in an On examination pulse was 100/min, tempera-
ambulatory manner—avoiding admission—and ture 38 °C, blood pressure 110/60 mmHg. The
encouraging oral fluid intake of 2–3 litres of fluid exit site of her tunneled catheter was clean.
per day, and commencement of a course of oral Blood cultures were sent. Her white cell and
antibiotics (amoxycillin + clavulanic acid 6750 mg CRP were raised.
orally tds for a 5 day course), with a view to being What is next best plan of management?
re-assessed by her local nephrology team in a A. Investigations for lupus nephritis.
week’s time, on return to her native country. B. Investigations for lymphoma
C. Start antibiotics for catheter related
bacteremia
Questions D. Start oral steroids
E. Start intravenous cyclophosphamide
1. A 22 year old black female presented with Correct answer: C mostly cause of fever is cath-
weakness, tiredness. On examination her eter related bacteremia and lupus id less likely.
pulse was 82/min, blood pressure was 4. A 55 year old asymptomatic man was admit-
165/80 mmHg and she had a red rash over her ted to hospital from the transplant clinic with
face. Urine examination showed blood and rising creatine 15 days post kidney transplant
protein. Blood test showed low haemoglobin from 150 to 230 μmol/L. He was on mycophe-
and creatinine was 187 μmol/L. nolate 250 mg bd and tacrolimus 2 mg bd. His
What is most likely diagnosis tacrolimus level was 5 ng/mL (target 10–15).
A. Henoch Schulein purpura His pulse was 78/min, blood pressure
B. Systemic amyloidosis 130/60 mmHg. His urine had no blood pr pro-
C. Systemic lupus erythematosus tein. Ultrasound of the transplanted kidney
D. Essential cyroglobinimia was normal.
E. Systemic vasculitis What is the likely cause of his AKI
Correct answer: young woman with low haemo- A. Acute rejection
globin, haemo-proteinura and rash is most B. Acute intestinal nephritis
likely to be lupus. C. Tacrolimus toxicity
2. A 45 year old black man presented with tired- D. Thrombotic microangiopathy related to
ness and frothy urine. On examination his pulse tacrolimus
was 89/min, blood pressure was 130/82 mmHg. E. Urinary tract infection
He had a white deposit over his tongue and
inner side of his cheek. His urine Test your learning and check your understand-
protein:creatinine ratio was 300 mg/mol ing of this book’s contents: use the “Springer
(Normal < 15). His kidney ultrasound showed Nature Flashcards” app to access questions. To
bilateral normal size bright echogenic kidneys. use the app, please follow the instructions below:
What is the likely cause of his nephrotic
syndrome? 1. Go to https://flashcards.springernature.com/
A. Amyloidosis login.
B. Type 2 diabetes 2. Create a user account by entering your e-mail
C. Hypertension address and assigning a password.
D. HIV associated nephropathy 3. Use the following link to access your SN
E. Systemic lupus nephritis Flashcards set: https://sn.pub/cz9Cok. If the
3. A 23 year old female with lupus nephritis, end link is missing or does not work, please send
stage kidney failure on haemodialysis pre- an e-mail with the subject “SN Flashcards”
sented with fever and lethargy. She denied and the book title to customerservice@spring-
Joint pain, dysuria, cough, diarrhoea or rash. ernature.com.
References analysis for the global burden of disease study 2017.

Lancet. 2020;395(10225):709–33.
2. Liyanage T, Ninomiya T, Jha V, Neal B, Patrice HM,
1. Bikbov B, Purcell CA, Levey AS, Smith M, Abdoli A,
Okpechi I, et al. Worldwide access to treatment for
Abebe M, et al. Global, regional, and national burden
end-stage kidney disease: a systematic review. Lancet.
of chronic kidney disease, 1990–2017: a systematic
2015;385(9981):1975–82.
AL GRAWANY
Investigating Kidney Disease
2
Mukunthan Srikantharajah, Rukma Doshi,
Debasish Banerjee , Vivekanand Jha ,
and Nicholas M. P. Annear
Clinical Scenario Introduction

A 50 year old male with a history of gout presents
to the general nephrology clinic with a serum cre- The signs and symptoms of kidney disease are
atinine of 178 μmol/L (2.01 mg/dL). He is other- often non-specific, so pertinent further investiga-
wise asymptomatic. His medications include tions can help either confirm or refute a diagnosis
allopurinol 200 mg po od, and ibuprofen 200 mg amongst differentials. For the kidney patient, key
po prn. There is no significant family history of investigations include blood tests, urinalysis,
kidney disease or hypertension. His blood pres- imaging studies, histopathology and electrocardi-
sure is 170/90 mmHg, his pulse 70 beats per min- ography (ECG). DNA analysis may also be help-
ute, but his physical examination is otherwise ful in determining the diagnosis where certain
unremarkable. clinical presentations are suggestive, or where
How would you proceed? there is a clear family history of kidney disease:
we will discuss this in more detail in a later chap-
ter. It is more often than not the combination of a
careful history and physical examination, taken
together with the results of key investigations that
help clinicians to clinch the diagnosis, and define
M. Srikantharajah
an appropriate management strategy [1–3].
Imperial College Kidney and Transplantation Throughout the course of this textbook, you
Institute, London, UK will encounter different kidney diseases and the
e-mail: m.srikantharajah@nhs.net investigative and management approach for each
R. Doshi individually. In this chapter, we will look broadly
Epsom and St. Helier Hospitals NHS Trust, Epsom, UK at the investigations commonly used to investi-
e-mail: r.doshi@nhs.net
gate patients with possible kidney disease.
D. Banerjee · N. M. P. Annear (*)
St George’s University of London, London, UK
St George’s University Hospitals Foundation Trust, Blood Tests
London, UK
e-mail: dbanerje@sgul.ac.uk; nannear@sgul.ac.uk
Alongside blood pressure and urinalysis, a sim-
V. Jha
The George Institute for Global Health,
ple blood biochemical test assessing the serum
New Delhi, India creatinine stands as perhaps the single most
e-mail: vjha@georgeinstitute.org.in widely used investigation for the practicing

https://doi.org/10.1007/978-3-031-09131-5_2
12 M. Srikantharajah et al.
nephrologist: as a cheap, well-validated and eas- inform the clinician about the potential cause of
ily available blood test, it is performed on most kidney disease, and infer the chronicity and com-
patients who attend hospital as an inpatient, and plications of kidney disease: we will set about
is frequently used to screen patients for kidney describing them as follows (Tables 2.1, 2.2, and
dysfunction in ambulatory, outpatient and com- 2.3).
munity settings. Understanding the timeframe
over which a serum creatinine result has become
abnormal can help determine whether a kidney Serum Biochemistry
impairment is either acute or chronic; and using
other widely available demographic data for the One of the key functions of the kidney is main-
patient, including gender, age, ethnicity, along- taining electrolyte homeostasis. Thus, measure-
side the serum creatinine, an estimate for the glo- ment of blood urea, creatinine, electrolytes and
merular filtration rate (GFR) can be made. pH can be used to assess the functions of the kid-
Alongside the serum creatinine, various other ney in filtering and reabsorbing electrolytes, thus
biochemical, haematological, immunological maintaining electrolyte concentrations and blood
and virological blood tests that are used to further pH within a ‘normal’ range.
Table 2.1 Serum biochemistry tests in kidney disease

Test (Abbreviation)
Normal values–SI
units (Conventional
units) Raised levels associated with Low levels associated with
Sodium (Na+) Fluid depletion Drugs (loop/thiazide diuretics; proton pump
133–146 mmol/L inhibitors (PPIs); antipsychotic/
(310–330 mg/dL) antidepressant medications); Syndrome of
inappropriate antidiuretic hormone secretion
(SIADH)
Potassium (K+) 1. Excess dietary intake; Drugs (loop/thiazide diuretics; renal tubular
3.5–5.3 mmol/L 2. Decreased excretion (AKI; decompensated disorders (e.g. Barter’s/Gitelman’s
(14–20 mg/dL) CKD; drugs e.g. potassium sparing syndromes)
diuretics; liquorice);
3. High cell turnover states e.g.
haematological malignancies
Bicarbonate Renal tubular disorders Insufficient renal production (decompensated
(HCO3−) AKI/CKD); drugs
22–26 mmol/L
Chloride (Cl−) Loss of body fluids from prolonged vomiting, Fluid loss/dehydration due to diarrhoea or
98–106 mmol/L diarrhoea, sweating or high fever (dehydration). vomiting
(340–370 mg/dL) High levels of blood sodium. Kidney failure, or
kidney disorders. Diabetes insipidus or diabetic
coma
Urea AKI; CKD; upper GI bleed Nutrient insufficiency/low muscle mass
2.5–7.8 mmol/L
(6–20 mg/dL)
Serum creatinine AKI; CKD; drugs (e.g. trimethoprim/ Nutrient insufficiency/low muscle mass
M 59–104 μmol/L co-trimoxazole)
(0.74–1.35 mg/dL)
F 45–84 μmol/L
(0.59–1.04 mg/dL)
Corrected calcium 1. Excess dietary intake/drugs Tertiary hyperparathyroidism
(cCa2+) 2. Decreased excretion Post parathyroidectomy ‘hungry bone
2.2–2.6 mmol/L 3. High bone turnover (e.g. primary/secondary syndrome’
hyperparathyroidism; malignant myeloma;
metastatic cancer)
2 Investigating Kidney Disease 13

Test (Abbreviation)
Normal values–SI
units (Conventional
units) Raised levels associated with Low levels associated with
Phosphate (PO43−) Drugs (e.g. vitamin D enhances dietary Hyperparathyroidism; vitamin D deficiency
0.87–1.45 mmol/L phosphate absorption)
(3.0–4.5 mg/dL) Decompensated CKD
Alkaline May be raised in liver dysfunction due to n/a
phosphatase infection, alcohol, drugs or biliary obstruction.
(ALP) When isolated, may indicate increased bone
30–130 U/L turnover
Albumin Fluid depletion 1. Insufficient production: Nutrient
35–50 g/L insufficiency/chronic inflammatory states;
(3.5–4.8 U/L) 2. Excess losses: nephrotic syndrome
Parathyroid Primary & secondary hyperparathyroidism Post parathyroidectomy/ectopic PTH
hormone (PTH) production
10–65 pg/L
Vitamin D Dietary excess Common in dietary insufficiency/seasonal
>50 nmol/L variation
Glucose Diabetes mellitus Insulinoma; exogenous insulin/oral
4.0–6.0 mmol/L antidiabetic drug administration
Ferritin May be raised in acute inflammatory states
M & PMF
12–300 ng/mL
(27–670 pmol/L)
F 12–150 ng/mL
(27–330 pmol/L)
Urate 1. Decreased excretion: Commoner in Dilutional
M 200–430 μmol/L progressive CKD; certain forms of
F 140–360 μmol/L inherited renal disease e.g. UMOD;
2. Increased production: high cell turnover
states e.g. haematological malignancy
Creatine kinase Increased muscle breakdown e.g. marathon Dilutional
(CK) running/gym workouts; drugs e.g. statins,
M 40–320 U/L antipsychotic medication; exclude compartment
F 25–200 U/L syndrome
C-reactive protein Acute and chronic infective or inflammatory n/a
(CRP) states, including active autoimmune conditions
<5 mg/L
SI international system, PMF post-menopausal females
Urea and Electrolytes Individuals with greater muscle bulk tend to have
a higher serum creatinine level at baseline, as are
Sodium, potassium, chloride and bicarbonate are individuals of black ethnicity, although the rea-
all small ions, which are freely filtered and son for this is uncertain. Serum creatinine is a
actively reabsorbed in the kidney. sensitive marker of kidney function, and increases
non-linearly as kidney function deteriorates.
Most filtered creatinine is excreted by the renal
Urea and Creatinine tubule. It is important to note that this excretion
can be blocked by certain medications such as the
Larger molecules like urea and creatinine are antibiotic trimethoprim/co-trimoxazole, which
excreted and not resorbed by the kidney. results in an increase in serum creatinine, that is
Creatinine is a waste product of muscle metabo- not related to a change in glomerular filtration
lism and is excreted by the kidneys into the urine. rate (GFR).
Table 2.2 Haematology tests in kidney disease Table 2.3 Immunolological and virological tests in kid-
ney disease
Test
(Abbreviation) Investigation Description
Normal Anti-neutrophil c-ANCA
values–SI units cytoplasmic Diffuse cytoplasmic staining,
(Conventional Causes of raised Causes of low antibody corresponding to antibodies
units) levels levels (ANCA)—marker against neutrophil proteinase-3
Haemoglobin Polycythaemia Deficient EPO of small vessel (PR3). Positive in 90% of patients
(Hb) may be primary, production by vasculitis with active granulomatosis with
M 130–180 g/L related to juxtaglomerular polyangiitis
F 115–165 g/L excessive EPO cells can lead to a p-ANCA
production in normocytic renal Perinuclear staining corresponding
polycystic kidney anaemia to antibodies against neutrophil
disease, or myeloperoxidase (MPO). Positive
upregulation of in 60% of patients with
hypoxia inducible microscopic polyangiitis and 30%
factor in tumour of patients with Churg-Strauss
conditions such as syndrome
VHL disease Anti-glomerular Positive in anti-GBM disease
White cell May be raised in May be reduced basement (Goodpasture’s disease). Patients
count (WCC) infection or in immune membrane can present “double positive”
Total WCC: proliferative states suppression, such (anti-GBM) (ANCA vasculitis plus the
3.6– as due to antibody presence of anti-GBM antibody)
11.0 × 109/L mycophenolate Anti-nuclear Many subtypes exist such as
mofetil antibody (ANA) anti-Ro, anti-La and anti-Sm
Neutrophils: Typically raised in May be reduced antibodies. Therefore, can be used
1.8–7.5 × 109/L bacterial infections in immune in the diagnosis of many
suppression, such autoimmune disorders
as due to Anti -dsDNA Positive in 50% of patients with
mycophenolate active SLE. Can be used to
mofetil monitor disease activity in SLE
Lymphocytes: May be raised in May be reduced Complement Low C3 + C4 (classical
1.0–4.0 × 109/L viral infections acutely in viral concentrations C3 complement pathway activation).
infections and C4 Used in SLE diagnosis and as a
Eosinophils: May be raised in marker of activity. Isolated
0.1–0.4 × 109/L interstitial reduction in C3 (alternate
nephritis complement pathway activation) is
Platelet count May be raised in May be reduced seen in C3GN and infection related
(Plt): acute in haemolytic GNs
140– inflammatory and states Cryoglobulins Present in various conditions
400 × 109/L infective associated with renal impairment
conditions (i.e. SLE, multiple myeloma,
Mean cell May be raised in Reduced in HIV). The most often quoted link
volume alcohol excess, microcytic is with Hepatitis-C related
(MCV): thyrotoxicosis, anaemia and membranoproliferative GN
80–100 fL B12 and folate β-thalassaemia Viral serology: Hepatitis B and Hepatits C—
deficiency—renal Hepatitis B, C and associations with membranous
anaemia is HIV nephropathy and
typically mesangiocapillary GN
normocytic HIV—associations with FSGS and
Haemoglobin Raised in poorly n/a HIV-associated nephropathy
A1c (HbA1c) controlled diabetes Virology is also key to perform
<42 mmol/mol mellitus when commencing patients on
(6%) dialysis or immunosuppression
Table 2.3 (continued) demographics has allowed the widespread

Investigation Description implementation of eGFR reporting, using the
Serum (and urine) Help detect production of single Cockroft-Gault (correction using weight and
protein immunoglobulins (monoclonal
age), CKD-modified diet in renal disease (CKD-
electrophoresis antibodies). Relevant in Myeloma
and Monoclonal gammopathy of MDRD), and latterly CKD- Epidemiology
renal significance Collaboration (CKD-EPI) formulae (Table 2.4)
Serum free light Can help detect myeloma or light to correct for age, gender and ethnicity, and
chains (Kappa κ chain deposition disease. Mostly of approximate the GFR. There are limitations in
and Lambda λ) significance when there is a
significant difference between the the accuracy of eGFR equations—with particu-
ratios of kappa to lambda light larly large variation in children, adolescents,
chains. Kidney disease can cause older adults, and different ethnicities, and with
elevation of both kappa and lamda higher eGFR >60 mL/min/1.73 m2, although
light chains
this has improved with latter modifications to
Anti-phopholipase A relatively new component to the
A2 receptor ‘renal screen’ (discovered in 2009) the formula. Other limitations include when cre-
(anti- PLA2R) [4]. Associated with Primary atinine excretion is directly blocked e.g. with
antibody membranous nephropathy (see trimethoprim/co-trimoxazole administration.
Chap. 12)
Importantly, most drug dosing recommenda-
tions are made based on Cockroft-Gault creati-
nine clearance, using age, weight and serum
The Glomerular Filtration Rate (GFR) creatinine.
Alternative biomarkers to measure eGFR
The Glomerular Filtration Rate (GFR), is the include measuring Cystatin C, which is an
rate of blood flow through the kidney—and is inert low molecular weight protein, produced
commonly decreased in kidney disease. Gold by all nucleated cells in the body, and which is
standard tests for measuring the GFR (mGFR) less influenced by muscle mass, gender and
include EDTA-GFR and iohexol. Each of these ethnicity. Levels of Cystatin C can still be
methods involve exogenous administration of a influenced by medications, obesity and smok-
molecule that is filtered freely by the kidney, ing, and the cost of measuring it remains sig-
and not actively reabsorbed. This involves cost nificantly higher than that of measuring serum
and complication, and low-level risk to the Creatinine. In global healthcare terms, its low
patient. Consequently, refinement of correcting cost and ready availability make serum
equations for serum creatinine measurements to Creatinine the most cost-effective marker of
accurately estimate the GFR using patient kidney function.
AL GRAWANY
Table 2.4 Equations commonly used to calculate the estimated Glomerular Filtration Rate (eGFR)
Cockroft-Gault Equation:
eGFR = (140 – age) x weight x 1.23 [if Male] OR 1.04 [if Female]
SCr
MDRD eGFREquation:
eGFR = 175 x (SCr)-1.154 x (age)-0.203 x 0.742 [if Female] x 1.212 [if Black]
CKD-EPI Equation:
eGFR = 141 x min(SCr/κ, 1)α x max(SCr/κ, 1)-1.209 x 0.993(age) x 1.018 [if Female] x 1.159 [if Black]
κ = 0.7 (Female) or 0.9 (Male)
α = -0.329 (Female) or -0.411 (Male)
min = indicates the minimum of SCr/κ or 1
max = indicates the maximum of SCr/κ or 1
eGFR (estimated glomerular filtration rate) = mL/min/1.73 m2

SCr (standardized serum creatinine) = mg/dL or µmol/L
Age = years
Urine Tests globin, myoglobin, proteins and crystals. For

example, patients with nephrotic syndrome
Urinalysis is a fundamental bedside test in help- commonly observe ‘frothy’ urine—a sign of
ing investigate kidney disease. Fresh ‘mid- proteinuria. Table 2.5 highlights some of the
stream’ urine is most valuable to help reduce commonly observed visual appearances of
accidental contamination. urine:
Urine should be dipped in a fresh mid-stream
urine specimen, and then left to dry on the side for
Appearance at least 1–2 min (depending on the manufacturer’s
recommendation), before being read against the
Visible inspection of the urine can provide manufacturer’s colorimetric chart on the bottle
clues towards a diagnosis: changes in urine (Fig. 2.1), or using an automated colorimeter
colour or consistency can be related to haemo- where this is available (Tables 2.6 and 2.7).
Table 2.5 Common appearances of urine
Urine appearance Significance

Clear, Dilute Well-hydrated /polyuric
Clear, Pale yellow Normal
Concentrated Fluid deplete / inadequate
hydration
Cloudy, turbid May indicate infection
Frothy Protein – acts like a detergent
and causes frothy or cloudy
urine
Orange Medications such as rifampicin,

sulfasalazine
Blue or green Dyes, food colouring,
medication including Propofol
and amitriptyline. Rarely by
Pseudomonas aeruginosa
Red Blood, rifampicin, food

colourings such as beetroot,
Brown Food such as fava beans.
Medication such as
nitrofurantoin and
metronidazole
Fig. 2.1 Image of urine dipstick analysis

Table 2.6 The ‘urine dipstick’/urinalysis
Urine dipstick component Significance

Leukocytes May indicate infection. Detected as leucocyte esterase
activity
Nitrites May indicate infection. Urinary nitrates are converted to
nitrites in the presence of Gram-negative bacteria which
produce nitrate reductase (e.g.Escherichia coli)
Protein Standard dipsticks measure albumin only but may fail to pick
up total protein as well as microalbuminuria (I.e. urine
albumin 3-30mg/mmol creatinine). Proteinuria may equate to
glomerular disease. Note – 70% of protein in the urine is
albumin
pH Normal urine pH is acidic. The pH can be used to investigate

renal stone disease and suspected renal tubular acidosis.
Blood/Haemoglobin May indicate haematuria (i.e. glomerular disease) however in
the absence of haematuria can be due to intravascular
haemolysis and rhabdomyolysis (myoglobinuria). Note – false
negative results can occur in the presence of high vitamin C
concentrations
Specific gravity The measure of the amount of solute dissolved in urine.

Low specific gravity (<1.005) – excess hydration / defect in
ability of kidneys to concentrate urine
High specific gravity (>1.035) – dehydration, glycosuria,
proteinuria, contrast
Ketones Ketonuria is associated with starvation, low carbohydrate

diets, diabetic ketoacidosis, hyperthyroidism and alcoholism
Glucose Positive when the serum glucose is high eg. Diabetes mellitus
Table 2.7 Summary of urine-based investigations when investigating kidney disease

Urine test Significance
Visual inspection & urinalysis See Tables 2.5 and 2.6
Microscopy Urine is examined under a light microscope to demonstrate the
presence of cells, bacteria, casts and crystals
Casts—these are cylindrical structures formed in the distal renal
tubules
Hyaline casts—Most common type, typically innocuous (seen
in concentrated urine i.e. dehydration)
Granular casts—can result from degenerating cellular casts.
Associated with inflammation and infection
Dysmorphic red cells and red blood cell casts—indicate
glomerular pathology
White cell casts—can suggest infection such as pyelonephritis
or tubulointerstitial nephritis
Crystals—certain drugs such as anti-virals can cause this
Eosinophils—suggests tubulointerstitial nephritis (TIN)
Urine culture Useful in identifying infection. Pyuria (>8 × 106 white cells/L)
without bacteriuria—think tuberculosis
Urine cytology May identify urinary tract malignancy

Urine test Significance
Urine protein quantification Urine ACR: measures only albumin—to help detect glomerular
24 h urine collections or single void specimens: disease
Albumin: creatinine ratio (ACR) Urine PCR: measures total protein. Therefore, will rise with
Or Protein: creatinine ratio (PCR) any protein detected in the urine (i.e. low molecular weight
proteins, light chains as well as albumin)
Urine PCR of 100 roughly equates to 1 g proteinuria per day
Osmolality Can help assess the ability of the kidneys to concentrate urine,
free water clearance and cause of hypo/hypernatraemia. More
accurate measure of urinary concentration than specific gravity.
Raised in SIADH
Sodium Fractional excretion of sodium (FeNa) can be used to determine
the type of AKI. Low urinary sodium suggests normal
reabsorptive function. High urinary sodium suggests renal salt
wasting
FeNa <1%—prerenal uraemia, hepatorenal syndrome
FeNa >2%—ATN, CKD, osmotic diuresis
A urine sodium >20 mmol/L may indicate diagnosis of ATN
Potassium If <20 mmol/L or low TTKG—extra-renal potassium loss
Chloride Can help distinguish between causes of metabolic alkalosis. A
urinary chloride <20 mmol/L in a patient with metabolic
alkalosis indicates volume contraction
Myoglobin Can identify rhabdomyolysis
Urinary Bence Jones protein This is an immunoglobulin light chain—its presence in urine is
suggestive of a monoclonal gammopathy of renal significance
(MGRS), or Multiple myeloma (MM)
TTKG transtubular potassium gradient = urine potassium / urine osmolality

serum potassium / serum osmolality
Radiological Imaging –– Air space opacification:
The imaging modalities most often used in the • Unilateral: when lobar and associated with
initial assessment of the kidney patient are plain lobar collapse, may be consistent with
film radiography of the chest, and urinary tract infection, and secondary AKI.
ultrasound. Cross-sectional imaging using com- • Bilateral: may be consistent with bilateral
puted tomography (CT) or magnetic resonance infection, pulmonary haemorrhage or—
imaging (MRI) is more frequently a second-line more commonly—fluid overload,
investigation. particularly when associated with pleural
effusions secondary to kidney failure or
nephrotic syndrome (this may also be sec-
Plain Radiography ondary to other transudative causes such as
cardiac or liver failure).
Chest X-Ray
Breathlessness is a common presentation in kid- –– Hilar lymph node enlargement (associated
ney disease, thus a chest radiograph may be used with infection, autoimmune and inflammatory
to look for evidence of: conditions such as sarcoidosis, and underlying
malignancy, particularly in the context of I ntravascular Contrast Studies

other spiculated lung lesions) Ultrasound has replaced most intravenous uro-
gram/intravenous pyelogram examinations of the
Abdominal X-Ray kidney.
Plain radiography of the abdomen (which can
include imaging of the kidney, ureters and blad-
der) is not commonly used to investigate kidney Ultrasound
disease. The renal outlines in plain films are
often obscured by bowel gas shadows. Renal In the work up of a patient with a raised serum
stones, namely calcium-containing, struvite creatinine, an ultrasound scan of the renal tract is
and cystine stones (radiopaque) can be identi- an invaluable non-invasive, first-line imaging
fied, however uric acid and xanthine stones modality. It can help determine kidney size,
(radiolucent) may not be effectively picked up asymmetry, structural abnormalities (including
(Fig. 2.2). differentiating between cystic or solid, and sim-
ple or complex renal parenchymal lesions), and
identify and localise causes of urinary tract
obstruction (Fig. 2.3).
Normal kidney size is approximately
10–12 cm and is normally proportional to height
(Table 2.8). Ultrasound findings can also reveal
Fig. 2.3 Ultrasound imaging of the kidneys. A normal

right kidney in the sagittal plane: the top of the ultrasound
image is anterior; the bottom is posterior. Right on the
image is towards the feet (caudal) and left is towards the
head (cranial). The right liver lobe overlies the kidney; the
Fig. 2.2 Plain abdominal X ray. Normal Plain abdominal right kidney cortex and medulla are well-differentiated;
X ray—no radio-opaque kidney stones are demonstrated the interpolar length has been measured as 108.2 mm.
within the kidneys, ureters or bladder; the bowel gas pat- Note areas of increased shadowing are produced by the
tern is normal ribs
Table 2.8 Causes of small and large kidneys on What Is the Resistive Index (RI)?
imaging
Small kidneys (<10 cm) Large kidneys (>12 cm) Resistive index (RI) = (Peak systolic veloc-
Chronic kidney disease Diabetes mellitus ity − End diastolic velocity)/Peak systolic
Renal artery stenosis Acromegaly
velocity.
Hypoplasia Amyloidosis
Lymphoma (Normal RI < 0.70)
Polycystic kidneys The resistive index (RI) is a calculated flow
parameter in ultrasound, derived from the max-
imum, minimum and mean doppler frequency
features related to chronic kidney disease, such shifts during the cardiac cycle. It works on the
as when the echo-consistency of the renal cortex principle that as a vessel narrows and resis-
is reduced compared to the medulla and the col- tance to flow increases, the RI will increase. It
lecting system. The loss of this ‘corticomedullary can be used to monitor a kidney transplant
differentiation’ is a sensitive but non-specific blood vessel flow, particularly in the early
marker of chronic kidney disease. post-transplant period. Causes for a raised RI
in the transplanted kidney are multiple, and
can be related to transplant renal vein and renal
Practice Point 1 artery thrombosis, acute tubular necrosis,
rejection, immunosuppressive toxicity, peri-
Orienting the ultrasound image: the top of nephric fluid collection, and transplant renal
the ultrasound image is the location where artery stenosis [5].
the sound waves enter the patient first—so
irrespective of position and tipping, the
skin will always be at the top. Computed Tomography (CT)
Cross-sectional urinary tract imaging using com-

puted tomography (CT) can be used to provide
Renal Doppler Ultrasound Scans additional or complementary information to the
ultrasound, namely because a sharper resolution
Doppler ultrasound is a specialised ultrasound is obtained. It can be used to delineate the cause
imaging that can evaluate the flow of blood in of obstruction and investigate masses in the kid-
renal arteries and veins. They can help assess for ney, including the staging of renal tumours. It is
renal vein thrombosis, renal artery stenosis, more effective at detecting ureteric calculi (non-
decreased renal perfusion and renal infarction. contrast CT) and can help delineate the level of
Renal artery stenosis—may be identified if ureteric obstruction. However, it is less sensitive
there is markedly peaked systolic velocity in the than ultrasound at differentiating between solid
renal artery, particularly when compared to aortic and cystic lesions in the kidney. CT angiography
peak systolic velocity. can help evaluate renal artery stenosis, in particu-
Renal vein thrombosis—Since the kidneys lar identifying the presence or absence of a post-
are deep and retroperitoneal, doppler ultrasound stenotic dilatation in the affected renal artery
of the native kidney is often insufficiently sensi- (Fig. 2.4).
tive to make a diagnosis of renal vein thrombosis Iodinated radio-opaque contrast, used for CT
(e.g. related to nephrotic syndrome), so CT or imaging, poses the risk of nephrotoxicity, with
MRI venography is preferred. However, trans- the risk deemed greater for those with underly-
plant renal ultrasound is often the modality of ing kidney impairment. Pre-hydration with oral
choice in diagnosing renal vein thrombosis in a or intravenous fluid can be effective in reduc-
transplanted kidney, where the blood vessels are ing the risk of contrast induced nephropathy.
typically relatively superficial. N-acetylcysteine is no longer recommended to
a b
Fig. 2.4 Computed Tomography (CT) imaging of normal kidneys. Coronal CT scan of the normal kidneys and blad-
der—without contrast (a) and following administration of iodinated contrast (b)
prevent contrast nephrotoxicity (due to lack of

any confirmed benefit). a
Magnetic Resonance Imaging (MRI)
Magnetic resonance imaging (MRI) can be an

effective method to study anatomical changes such
as renal tumours, atherosclerotic vascular disease
and renal vein thrombosis. Soft tissues are also
visualised in greater detail than with CT or radiog-
raphy; MRI has the additional benefit of no radia-
tion exposure. MRI helps better delineate wall
thickening and nodularity of renal lesions when
compared to CT or ultrasound. This imaging
modality also has a role in evaluating indeterminate
renal lesions (i.e. diffusion weighted MRI may
help in differentiating between inflammatory and b
malignant masses). Magnetic resonance angiogra-
phy (MRA) with gadolinium can also be used to
study renal artery stenosis, with greater accuracy
than when compared to ultrasound [6] (Fig. 2.5).
Most MRI scanners comprise a very tight tun-
nel, and a loud ‘banging’ noise throughout the
scanning process, which may make it difficult for
patients who suffer with claustrophobia to toler-
ate. The advent of ‘open MRI’ scanners at certain
centres may improve tolerability, but depending
Fig. 2.5 Magnetic Resonance Imaging (MRI) of normal
on availability, may also be in greater demand,
kidneys. Coronal (a) and Axial (b) T2-weighted MRI of
leading to delays in the diagnostic process. the normal kidneys
uclear Medicine Imaging: Renal

N
Practice Point 2 Scintigraphy
• T1 MR images: 1 tissue type is
bright—FAT Renal scintigraphy refers to several nuclear medi-
• T2 MR images: 2 tissue types are cine examinations for the kidney using radiophar-
bright—FAT & WATER maceuticals that evaluate the function and anatomy
of the kidneys. Each of these techniques involve
the injection of a radiopharmaceutical or radio-
tracer that emits a tiny amount of radioactivity into
ephrogenic Systemic Fibrosis
N the patient. After injection, the radiotracer travels
The use of gadolinium has been linked to the throughout the body to the kidneys, where it gives
development of nephrogenic systemic fibrosis off energy in the form of gamma rays. This energy
(NSF). This is a rare syndrome that can involve is detected by a device called a gamma camera.
fibrosis of skin, joints, eyes and internal organs. The camera works with a computer to produce
This is a particular risk to patients with end- special pictures offering details on both the struc-
stage kidney disease, and it remains recom- ture and function of organs and tissues.
mended that gadolinium-containing contrast The different properties of each radiotracer
should be avoided in patients with an eGFR of allows for different information to be gleaned
<30 mL/min/1.73 m2. As there is no definitive from each approach (Table 2.9). The three main
cure for this condition (although improvements radiopharmaceuticals used are: Technetium-99m
in NSF symptoms have been seen following diethylene triamine pentaacetic acid (99mTc-
kidney transplant), ultimately treatment focuses DTPA) and Technetium-99m mercaptoacetyltri-
on avoidance of the condition through minimis- glycine (99mTc-MAG3), Iodine-131-Hipuran
ing the use of gadolinium contrast where (131I-Hipuran), Technetium-99m glucoheptonate,
possible. and Technetium-99m dimercaptosuccinic acid
Table 2.9 Comparison of different renal nuclear medicine imaging modalities

Tc-DTPA
99m 99m
Tc-MAG3 I-Hipuran
131
Tc-Glucoheptonate 99mTc-DMSA
99m
• Filtered through • Filtered through • Excreted by renal • Binds to renal • Binds to renal
the glomerulus the glomerulus tubules cortex cortex
• Excreted by renal
tubules
Perfusion • Perfusion • Diminished renal – Renal scarring • Renal scarring
• Vascular supply • Vascular supply function from chronic from chronic
– Filtration – Filtration • Kidney infection— infection
• Measuring renal • Measuring renal transplants Infarction • Infarction
function function – Renal mass • Renal mass
(glomerular (glomerular – Differential renal • Differential renal
filtration rate) filtration rate) mass (proportion mass (proportion
– Drainage • Drainage of total renal of total renal mass
• Detects Detects obstruction mass contributed contributed by
obstruction • Diminished renal by each kidney) each kidney)
function
• Kidney
transplants
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(99mTc-DMSA). Local availability of radioiso- ney biopsy) to obtain sample cores. Following the
topes is absolutely key to obtain simple radioiso- procedure, patients are required to have a period of
tope imaging. bed rest (6–8 h), during which their vital signs are
measured, and their urine monitored for visible
haematuria (around 1:100). Bleeding is the major
Histopathology primary complication; in rare cases this may lead
to significant retroperitoneal haemorrhage (around
A definitive diagnosis of kidney disease—partic- 1:1000) and the need for blood transfusions, and
ularly in diagnosing and grading severity of tubu- either radiological or surgical intervention to stop
lointerstitial nephritis, glomerulonephritis and the bleeding. There is also a very small risk of
transplant rejection—often requires the direct death (<1:1000). The decision to undertake a kid-
examination of kidney tissue, which is obtained ney biopsy should therefore be made after careful
by percutaneous kidney biopsy. This is most evaluation of the risks and benefits of the procedure
often ultrasound or CT-guided, in order to mini- to the patient [7–8].
mise complications.
Indications
Kidney Biopsy
Kidney biopsies can help confirm a diagnosis
Despite medical advancements in recent years, the (in particular for suspected glomerular patholo-
needle core kidney biopsy remains an invaluable gies), evaluate disease activity or establish dis-
tool for the nephrologist: It is an invasive investiga- ease stage/severity (e.g. lupus nephritis) and
tion, in which samples of kidney tissue are obtained hence help determine disease prognosis
for histopathological study. Usually performed (Table 2.10).
with local anaesthetic, with or without sedation, Although kidney biopsies have an invaluable
and under ultrasound or CT guidance, a specialised role in providing a definitive diagnosis, there are
biopsy needle is guided retroperitoneally via the certain situations where they are relatively or
patient’s back (native kidney biopsy—normally absolutely contraindicated, as the risk of the pro-
taken from the left lower pole when the anatomy is cedure potentially outweighs any conceivable
uncomplicated) or anteriorly over (transplant kid- benefit from a result (Table 2.11).
Table 2.10 Indications for renal biopsy
Indications forrenal biopsy

1.Acute kidney injury (after ruling out pre-renal and obstructive causes)
2.Unexplained chronic kidney disease
3.When suspecting glomerular pathology (acute glomerulonephritis andnephrotic
syndrome)
4.Systemic diseases with kidney involvement
5.Kidney transplant dysfunction
Table 2.11 Contraindications to renal biopsy
Relative Absolute
Single functioning kidney Small kidneys
Limited patient cooperation Uncorrectable bleeding diathesis / intravascular
coagulopathy
Technical difficulties (for example due to Uncontrolled hypertension
large body habitus / unable to lie flat)
Light and Electron Microscopy Table 2.12 Different histochemical stains and their rela-
tion to renal histopathology
The kidney tissue samples are typically collected Stain Significance

in formaldehyde for light microscopic evaluation, Haematoxylin & Evaluation of all four renal
Eosin (H&E) compartments and inflammation
and, depending on centres—specialist fixation Periodic To examine the glomerular cell
fluid for electron microscopic and RNA extraction acid-Schiff number, basement membrane,
where this is available and appropriate. An unfixed (PAS) mesangium, tubular basement
core is needed if immunofluorescence technique is membrane, hyaline—red
Masson’s To assess fibrin, fibrosis and
used. Sometimes, a same-day preliminary result
trichrome immune deposits. Extracellular
may be available and help guide immediate man- glomerular matrix and tubular
agement of the kidney patient—but fixation of the basement membranes—blue/green
sample can take up to 4 h of intense laboratory Silver stain To assess the basement membrane
work, so a same-day result requires careful coordi- (i.e. to visualise spikes and double
contours)—black and extracellular
nation, clear communication and swift transport glomerular matrix
between the clinician undertaking the biopsy, the Congo Red Amyloid
histopathology laboratory team, and thence to the Von Kossa Calcification
reporting histopathologist. Acid Fuchsin- Protein deposition (immune
Orange G complex)
Sirius Red Fibrosis
Light Microscopy (LM)

• immunoglobulins (IgA, IgG, IgM) (Fig. 2.7)
The light microscope uses visible light and a • components of the classical and alternative
series of lenses to magnify cells from the biopsy complement pathways (C1q, C4)
sample up to a maximum magnification of around • light chains (Kappa and Lambda)
×2000. Tissue samples are usually fixed in for-
malin, processed, cut into thin 2–3 micron thick
serial sections and stained with Haematoxylin Electron Microscopy
and Eosin (H&E) to enhance tissue contrast
under the light microscope. This stain is helpful Electron microscopes use an electron beam
for general evaluation of the biopsy specimen (all (rather than a light beam) to create an image of a
4 compartments; glomerular, tubular, interstitial specimen. They are able to visualise samples
and vascular). For kidney biopsies, there are using a much higher magnification—of around
additional specialised stains used to examine the ×1,000,000, so the kidney tissue can be visual-
pathology (Table 2.12 and Fig. 2.6): ised to a resolution of around 0.2 nm. The kidney
tissue is fixed in glutaraldehyde paraformalde-
hyde, and stained with toluidine blue to confirm
Immunohistochemistry the presence of glomeruli, after which the biopsy
sample can be studied in greater detail (Fig. 2.8).
Immunohistochemical techniques are used to
detect antigens by using ‘tagged’ antibodies, spe-
cific for that antigen. Antibodies can be conjugated Tissue Examination
to an enzyme that catalyses a reaction resulting in a and Interpretation
colour change. Antibodies can also be tagged with of the Histopathological Report
a fluorescent compound that emits light on excita-
tion by light. Specialised light microscopes can When examining a kidney biopsy specimen, ini-
then be used to examine these samples. Certain tially a low-power screening examination is use-
antigens are routinely looked for, including: ful to highlight any areas or defects. Furthermore,
a b
c d
e f
Fig. 2.6 Renal histopathological stains under light stain illustrating amyloid deposition in the glomerulus (e);
microscopy. Haematoxylin & Eosin (H&E) stain (a); Apple green birefringence under polarised light reflecting
Periodic Acid Schiff (PAS) stain (b); Masson’s Trichrome amyloid deposition in the glomerulus (f); Sirius red stain
stain (c) and Silver stain (d) of the normal glomerulus of the normal kidney (g)
under light microscopy at ×40 magnification; Congo red
Fig. 2.6 (continued) Fig. 2.7 Immunohistochemical staining. Immunoperoxidase

staining for IgA deposition showing mesangial distribution
of deposits in the glomerulus
Fig. 2.8 Electron Microscopy Imaging. Annotated Electron Microscopy Image at ×1000 magnification of the normal
glomerulus
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288 R. G. Sritharan et al.
Table 15.11 Diagnosis & Management of Tuberous Sclerosis Complex (TSC)§ [13, 14]
15 Genetic Kidney Diseases 289
Abbreviations: AD Autosomal dominant, AML Angiomyolipoma, ECG Electrocardiogram, EEG Electroencephalogram,

HRCT High resolution computerised tomogram, LAM Lymphangioleimyomatosis, MRI Magnetic resonance imaging,
mTOR Mechanistic target of rapamycin, SEGA Subependymal giant cell astrocytoma, TAND TSC-associated neuropsy-
chiatric disorders, TSC Tuberous sclerosis complex
Glomerular Diseases 15.12. The diagnosis and management of atypi-

cal HUS and C3 Glomerulopathy is summarised
Multiple genetic disorders cause glomerular in Table 15.13, and that of Fabry Disease in
diseases, as illustrated in Fig. 15.4 and Table Table 15.14.
Glomerular diseases
• Congenital steroid-resistant nephrotic syndrome (SRNS)
• Pierson syndrome
• Denys-Drash syndrome (DDS); Frasier syndrome; WAGR syndrome
• Nail-patella syndrome
• Schimke immuno-osseous dystrophy
• Mitochondrial disorders with SRNS
• Glomerulopathy with fibronectin deposits
• Alport syndrome
• Alport syndrome with leiomyomatosis
• Fechtner syndrome (Al port syndrome with macrothrombocytopaenia)
• Benign familial haematuria (thin basement membrane disease/TBMN)
• Alstrom syndrome
• C3 glomerulopathy (C3G)
• Atypical Haemolytic Uraemic Syndrome (aHUS)
• Fabry disease
• Familial amyloidosis
Glomerulus Proximal convoluted tubule
Afferent arteriole
Distal
convoluted tubule
Efferent arteriole
Bowman’s
capsule
Thick
ascending limb
Collecting Duct
Loop of Henle
Fig. 15.4 Glomerular Diseases

Table 15.12 Glomerular disorders [3]

(continued)
Abbreviations: ACEi Angiotensin converting enzyme inhibitor, AD Autosomal dominant, aHUS Atypical Haemolytic
uremic syndrome, AR Autosomal recessive, CKD Chronic kidney disease, CNI Calcineurin inhibitor, CP
Cyclophosphamide, CYA Cyclosporin, CS Corticosteroids, DDS Denys-Drash Syndrome, DMS Diffuse mesangial scle-
rosis, EM Electron microscopy, ESKD End stage kidney disease, FSGS Focal segmental glomerulosclerosis, GBM
Glomerular basement membrane, LVH Left ventricular hypertrophym, LM Light microscopy, MCD Minimal change
disease, MMF Mycophenolate mofetil, Mt Mitochondrial inheritance, RAASi Renin-angiotensin-aldosterone system inhi-
bition, SRNS Steroid resistant nephrotic syndrome, TBMN Thin basement membrane nephropathy, WAGR Wilms tumour/
aniridia/genitourinary problems
Table 15.13 Diagnosis & Management of atypical haemolytic uremic syndrome (aHUS) and C3 glomerulopathy# [16]
Atypical haemolytic uraemic syndrome (aHUS) and C3 glomerulopathy (C3G)[14]
aHUS
Ultra-rare; characterised by AKI, thrombocytopenia & MAHA
>50% of aHUS patients have underlying inherited and/or acquired complement
abnormality
Eculizumab (a humanized anti-C5 mAb) enables control of aHUS, preventing progression
to ESKD (plasma exchange therapy can be used where eculizumab unavailable)
Triggers include autoimmune conditions, transplants, pregnancy, infections, drugs and
metabolic conditions
Clinical
Although time course & persistence not well understood, many patients appear at life-
Presentation
long risk for recurrent acute presentations[14]
C3G
C3G characterised by uncontrolled activation of complement cascade, leading to
glomerular C3 deposition
Dysregulation of C3 convertase driven by genetic and/or acquired defects
Majority of C3G patients follow a chronic, indolent course with persistent alternative
pathway activation, resulting in a 10-year kidneysurvival of around50%[14]
aHUS C3G
- Measure ADAMTS13 activity to - Measure serum/plasma
diagnose or exclude TTP complement levels ;
Laboratory
- Investigate for STEC-HUS - Test complement activity:
Analysis
- Measure serum/plasma required to define type/degree of
complement levels complement deregulation
Genetic - Genetic testing recommended for - Benefit of genetic analysis in C3G
Diagnosis patients in whom discontinuation currently unclear since our
of eculizimab is being considered understanding of genetic basis for
C3G remains incomplete
Genetic
- Minimum gene panel that should be screened in aHUS & C3G includes
Testing
CFH, CD46, CFI, C3, CFB, THBD, CFHR1, CFHR5, and DGKE
- Because of frequent concurrence of genetic risk factors in aHUS, analysis
should include genotyping for risk haplotypes CFH-H3 and MCP
- Genetic analysis essential in live-related kidney donor transplantation
Management
Treatment approach in aHUS[14]

Treatment approach inaHUS[14]
Transplant considerations aHUS

Management Recurrence Risk Treatment Regimen
HIGH RISK (50-100%) Prophylactic eculizumab
Previous early recurrence NB. Start on day of transplantation due to potential
Pathogenic Mutation severe recurrence and limited recovery of function in
Gain-of-function mutation kidney allografts compared with native kidneys
MODERATE RISK Prophylactic eculizumab or plasma exchange
No mutation identified
Isolated CFI mutations
Complement gene mutation
of unknown significance
Persistent low titre FH
autoantibody
LOW RISK (<10)% No prophylaxis
Isolated MCP mutations
Persistently negative FH
autoantibodies
Treatment approach in C3G

Optimal BP control: ACEi/ARBs
All
Optimal nutrition
patients
Lipid control
Description
Urine protein >500mg/24h despite supportive therapy, or
M oderate Moderate inflammation on kidney biopsy, or
disease Recent increase in serum creatinine suggesting risk of progressive disease
Recommendation
Prednisolone – short course (2-3 months) for anti-inflammatory effect
Mycophenolate mofetil
(continued)

Description
Urine protein >2000mg/24h despite immunosuppression and supportive
therapy, or
Severe inflammation presented by marked endo- or extra-capillary
proliferation with/without crescent formation despite
Severe immunosuppression and supportive therapy, or
disease Increased serum creatinine suggesting risk of progressive disease at onset
despite immunosuppression and supportive therapy
Recommendation
Limited success of anti-cellular immune suppressants and
methylprednisolone pulse dosing in rapidly progressive disease
Data insufficient to recommend eculizumab as first-line treatment of
rapidly progressive disease
Transplant considerations in C3G

Recurrence Treatment Regimen
Risk
Avoid transplantation during acute period of renal loss
Avoid transplantation during acute inflammation
Timing NO data to support association between specific complement
abnormalities (e.g. high titre C3NeF/low C3/high soluble C5b-9) &
increased risk of relapse
No specific recommendation can be made on donor choice
Donor
When considering living donors, high risk of recurrence should be
Selection
weighed against presumed risk of waiting on deceased donor list
Histological recurrence of C3G is as high as 90%
Limited data suggests that rapid progression to ESKD in the native
kidneys increases risk of recurrence
No known strategies to reduce risk of recurrence
Risk
Clinical recurrence should drive the decision to treat
reduction
In the absence of a clinical trial, the use of anti-complement therapy is
based solely on a small open-label trial and positive case reports
C3G-associated with monoclonal gammopathy has a high rate of
recurrence
Liver transplantation can be considered for kidney transplant recipients with liver-derived
complement protein abnormalities, uncontrolled disease activity despite eculizumab
therapy, or financial considerations regarding cost of long-term eculizumab therapy[14]
Abbreviations: ACEi Angiotensin converting enzyme inhibitors, AKI Acute kidney injury, ARB Angiotensin receptor
blocker, BP Blood pressure, C3NeF C3 nephritic factor, ESKD End stage kidney disease, mAb Monoclonal antibody,
MAHA Microangiopathic haemolytic anaemia, STEC-HUS Shiga toxin E. coli-associated haemolytic uraemic syn-
drome, TTP Thrombotic thrombocytopenic purpura
#
is shorthand reference for where aHUS and C3G are referenced in other tables in this chapter
Table 15.14 Diagnosis & Management of Fabry Disease (FD)### [17]

Fabry Disease (FD) [17]
Clinical Presentation • FD is an X-linked recessive lysosomal storage disorder
• Though X-linked, both males and females can be affected
• Deficient activity of α-galactosidase A results in accumulation of glycosphingolipids
with terminal α-D-galactosyl residue, particularly globotriaosylceramide (GL-3, Gb3,
CTH) and globotriaosylsphingosine (Lyso-GL-3, lyso-Gb3)
• Lipids progressively accumulate in the circulation, all cell types and organs, resulting
in multisystem involvement
• Type 1 “classic” males: little or no functional α-Gal A enzymatic activity (<3% of
normal mean activity).
• Major symptoms in childhood/adolescence: acroparaesthesias; angiokeratomas;
anhidrosis/hypohidrosis; gastrointestinal symptoms (abdominal pain, cramping,
frequent bowel movements); star-burst pattern corneal dystrophy on slit-lamp
examination (vision unaffected); Cardiac deposition leads to arrhythmias, LVH, and
HCM; kidney deposition: progressive proteinuria, CKD, ESKD; Cerebrovascular
deposition: TIAs, strokes
• Incidence of Type 1 disease is around 1:18,000 to 1:95,000
• Heterozygous females from Type 1 families display variable phenotype, due to random
X-chromosomal inactivation: ranges from asymptomatic to as severe as Type 1 males;
around 90% have classic star-burst pattern corneal dystrophy
• Type 2 “later-onset” males: residual α-Gal A activity, lack GL-3/Gb3 accumulation in
capillaries and small blood vessels.
• Normal childhood & adolescence, typically present with kidney/cardiac disease in third
to seventh decades
• Most Type 2 patients identified by enzyme screening of patients in cardiac,
haemodialysis, kidney transplant, stroke clinics, and by newborn screening
• Incidence of Type 2 disease is around 5–10 times more frequent than that of type 1
males
• Heterozygous females from Type 2 families may be asymptomatic or develop kidney or
cardiac manifestations later in life; Lack corneal or other early type 1 manifestation,
typically display less frequent and less severe disease than Type 2 male relatives
Genetic Diagnosis • Diagnosis established in males by α-galactosidase A–specific activity <25–30% of
control in peripheral white blood cells
• GLA mutations on X-chromosome
• Wide phenotypic variability, even amongst patients with same mutation
• FD should be considered and tested in patients with CKD, with no definitive cause of
nephropathy, especially familial cases
Management General principles
• ERT with recombinant human α-galactosidase A (agalsidase) is only currently available
therapy aimed at the aetiology of FD
• Development of signs or symptoms related to FD is an indication to start ERT:
• implies development of CKD, if ERT not already commenced for non-kidney
manifestations e.g. pain [17]
• ERT slows the progression of CKD in FD and reduces progression of HCM, especially
when commenced prior to established fibrosis [17]
• Individual FD patients should follow the general guidelines for management of CKD,
including BP optimisation, smoking cessation, dietary salt restriction, and management
of hyperlipidaemia [17]
Abbreviations: BP Blood pressure, CKD Chronic kidney disease, ERT Enzyme replacement therapy, ESKD End stage
kidney disease, HCM Hypertrophic cardiomyopathy, LVH Left ventricular hypertrophy, TIA Transient ischaemic attack
Kidney Tubular and Metabolic in those tubule segments (Causes of genetic kid-
Diseases ney tubular and metabolic diseases are sum-
marised in Fig. 15.5 and Table 15.15). The
In primary kidney tubulopathies, the primary diagnosis and management of X-linked hypo-
genetic defect causes loss of function of a spe- phosphataemia is detailed in Table 15.16, that of
cific kidney transport protein or signalling mole- Gitelman Syndrome (GS) in Table 15.17, and
cule. As certain transport systems are expressed that of Cystinosis is detailed in Table 15.18. In
Proximal convoluted tubule

• Renalalycosuria TypesA/B/0
• Proximal renal tubularacidosis (pRTA)Type 2
• X-linked hypophosphataemia (XLH)
• Hereditary hypophosphataemic rickets with hypercalciuria (HHRH)
• Hypophosphataemic nephrolithiasis or osteoporosis
• Combined proximal & distal RTA Type 3 Distal convoluted tubule
• 11-β hydroxylase deficiency
• Primary Fanconi renotubular syndrome
• Renai hypouricaemia (RHUC) • 17-α hydroxylase deficiency
• Glycogen storage disease Type 1 (GSDIA/GSDIB) •Gitelman syndrome (GS)
• Fanconi-Bickel syndrome (FBS) (hepatorenal glycogenosis) • Isolated dominant hypomagnesaemia
• Lysinuric protein intolerance (LPI) • Isolated autosomal recessive hypomagnesaemia
• Lowe syndrome (oculo-cerebro-renal syndrome) • Hypomagnesaemia with secondary hypocalcaemia
• Cystinosis
• Cystinuria Types A/B Distal
• Dent's Disease Types 1 and 2 convoluted tubule
Proximal convoluted tubule

Afferent
arteriole
Efferent
arteriole
Glomerulus
Bowman’s
capsule
Thick
ascending limb
Loop of Henle
Thick ascending limb

•Bartter syndrom Types 1-4
•Familial hypomagnaesaemia with hypercalciuria and nephrocalcinosis (FHHNC: FHHN/FHHNCOI)
•Autosomal dominant hypocalcaemia with hypercalciuria
Collecting Duct
Collecting duct
•Glucocorticoid-remediable aldosteronism (GRA)
•Distal renal tubular acidosis (dRTA)Type 1
•RTA with deafness
•SeSAME syndrome (EAST syndrome)
•Liddle syndrome
•Pseudohypoaldosteronism Types 1a & 1b
•Pseudohypoa ldosteronism type II (Gordon's syndrome)
•Nephrogenic diabetes insipidustypes 1 & 2
Fig. 15.5 Kidney Tubular and Metabolic diseases

Table 15.15 Kidney Tubular and Metabolic Diseases [3]

Gene symbol,
Characteristic signs and
Genetic Disorder MOI (gene Management
features
product)
Proximal Convoluted Tubule (PCT)
Asymptomatic in most;
polyuria, polydipsia;
Type A: low threshold for
Renal glycosuria
glucose excretion + no treatment required for
AR reduced TmG; SLC5A2 : most patients
Type A
AD Type B: low threshold for SGLT2 Monitor for development of
Type B
glucose excretion + type 2 diabetes mellitus
Type O
normal TmG;
Type O: no tubular glucose
reabsorption
Prevent growth abnormalities
Early onset;
Life-long bicarbonate
Failure to thrive (short
replacement therapy
stature, learning disability);
Proximal renal AR SLC4A4: Diuretics e.g. amiloride
Corneal opacities;
tubular acidosis AD NaHCO3 co- (reduce K+ loss)
Severe acidosis,
(pRTA) Type 2 transporter 1 Thiazide/loop diuretics
hyperchloraemia,
(reduce HCO3 loss - BUTmay
mild hypokalaemia;
aggravate hypokalaemia)
Rickets, osteomalacia
Vit. D3 & PO4 supplementation
Vit. D resistant
rickets/osteomalacia;
X-linked hypo-
hypophosphataemia; PHEX :
phosphataemia XD See table 16
hypocalciuria; FGF23
(XLH)±
urinary PO4 wasting;
normal Vit. D/Ca2+
hypophosphataemic rickets;
Hereditary hypo-
short stature;
phosphataemic SLC34A3 : Oral PO4 supplements
hypercalciuria;
rickets with AR Na+/PO4 co- AVOID active Vit. D analogs
urinary PO4 wasting;
hypercalciuria transporter 2C (may worsen hypercalciuria)
nephrocalcinosis;
(HHRH)
elevated 1,25(OH) Vit. D
Adult onset;
SLC34A1:
Hyposphataemic hypophosphataemia; phosphate supplementation
NP2a
nephrolithiasis AD hypercalciuria; low-dose Vit. D
SLC9A3R1:
or osteoporosis recurrent urolithiasis; supplementation
NHERF1
osteoporosis/fractures
Very rare;
mild metabolic acidosis;
learning disability;
Combined CA2 :
cerebral calcification; Na+ or K+ bicarbonate
Proximal & Distal AR carbonic
cranial hyperostosis; K+ supplementation
RTA Type 3 anhydrase 2
malocclusion;
short stature;
osteosclerosis; osteopetrosis
polyuria: loss of LMW solutes
SLC34A1: (AR)
(amino acids/Glu/
NP2a
LMW proteins/
GATM: (AD) symptomatic treatment;
Primary Fanconi AR organic acids/carnitine/
glycine fluid, electrolyte & nutrient
renotubular AD Ca2+/PO4-/K+/HCO3-) & H2O -
amidino- supplementation;
syndrome leads to hyperchloremic
transferase KRT; kidney transplant
metabolic acidosis; failure to
EHHADH: (AD)
thrive; rickets; normoglycemic
LBFP
glycosuria;

nephrocalcinosis &
nephrolithiasis less common.
impaired proximal tubular
urate reabsorption:
Increased fluid intake
low serum uric acid; SLC22A12:
Renal urine alkalization
high urinary urate; URAT1
Hypouricaemia AR xanthine oxidoreductase
urate nephrolithiasis; SLC2A9:
(RHUC) inhibitors may protect from
haematuria; pyelonephritis; GLUT9
EIAKI
nephrocalcinosis;
exercise-induced AKI
Hypoglycaemia;
Fanconi-like syndrome;
nephrocalcinosis;
hyperuricaemia;
hepatomegaly; G6PC : Frequent meals,
hyperlipidaemia; glucose-6- NG feeding, raw starch (to
Glycogen Storage lactic acidosis; phosphatase avoid hypoglycemia);
Disease Type 1 early: enlarged kidneys; (GSDIA) Oral NaHCO3
(GSDI) late: glomerular hyper-
AVOID fructose/galactose (to
AR filtration; proteinuria,
progressive CKD; SLC37A4: correct acidosis)
Type 1A (GSDIA)
growth retardation; Glucose-6- additional medication
Type 1B (GSDIB)
osteopenia; round face; Phosphate & organ transplant may be
platelet ± neutrophil Transporter necessary
dysfunction; enteropathy; (GSDIB) GCSF for neutropenia (GSDIB)
hepatic adenoma/carcinoma
GSDIB: neutropaenia
glycogen storage disease: liver replace fluid and electrolytes
Fanconi Bickel & kidney accumulation; Vit. D and PO4
syndrome (FBS) kidney tubular dysfunction; SLC2A2: supplementation
(hepatorenal AR hypoglycaemia; Small, frequent meals
GLUT2
glycogenosis) failure to thrive; polyuria; Fructose-predominant,
rickets; hepatosplenomegaly Galactose-restricted diet
Nausea & vomiting after

protein-rich meal;
Lethargy/coma;
failure to thrive; muscle
weakness; metabolic acidosis
Patients unable to metabolise
Fanconi syndrome; SLC7A7:
lysine, arginine or ornithine:
Lysinuric protein hypophophataemia; y+L amino
AR
intolerance (LPI) hypercalciuria; acid
protein-restricted diet
nephrocalcinosis; transporter 1
ammonia scavenging therapy
hyperammonaemia;
osteoporosis;
hepatosplenomegaly;
pulmonary alveolar
proteinosis; CKD
Thick Ascending Limb (TAL)
salt-losing tubulopathy with SLC12A1: aggressive Na+ & K+
secondary (Type 1) replacement;
hyperaldosteronism: KCNJ1: aldosterone antagonists,
hypokalaemic alkalosis; (Type 2) spironolactone, ACEi:
Bartter hypercalciuria, CLCNKB: counteract effects of
AR
syndrome types (hypocalciuria in Type 3); (Type 3) AII/aldosterone;
1–4 XR high renin; alkalosis; polyuria; BSND NSAIDs: Indomethacin/
failure to thrive; (Type 4A) Ibuprofen – to decrease
Types 1 & 2: antenatal CLCNKA & prostaglandin excretion;
polyhydramnios, dehydration, CLCNKB: growth hormone
(continued)

failure to thrive (Type 4B)
Type 4: deafness MAGED2:
(Type 5), XR
Median age of onset 1-8 years Supportive management
Hypo-
Hypomagnaesemia; CLDN16: Mg2+ replacement
magnesaemia
hypercalciuria; claudin 16 check for hypokalaemia/
with
nephrocalcinosis; progressive (FHHN) hypocalcaemia
hypercalciuria AR CKD/ESKD; seizures; CLDN 19 : thiazide diuretics
and
Ocular involvement with claudin 19 manage CKD/ESKD
nephrocalcinosis
CLDN19 mutations, termed (FHHNCOI) KRT: kidney transplant
(FHHNC)
FHHNCOI Lens implants for FHHNCOI
Pseudo-Bartter syndrome; CASR:
Autosomal Hypocalcaemia: tetany, Calcium
seizures; low PTH; sensing Ca2+ supplementation
dominant
hypercalciuria: receptor Low dose Vit. D (can increase
hypocalcaemia AD
nephrocalcinosis; ectopic GNA11: urine Ca2+ & risk of
with
and/or basal ganglia G-protein nephrocalcinosis)
hypercalciuria
calcification subunit α-11
Distal Convoluted Tubule (DCT)
Glucocorticoid replacement
therapy;
suppressed aldosterone; Treat hypertension;
CYP11B1:
11-βhydroxylase hypokalaemia; elevated MDT approach;
AR 11-β
deficiency androgen levels; Surgical reconstruction of
hydroxylase
virilisation ambiguous genitalia;
prenatal dexamethasone
Glucocorticoid replacement
suppressed aldosterone; therapy;
CYP17A1: Treat hypertension with
17-αhydroxylase hypokalaemia;
AR 17-α mineralocorticoid antagonist
deficiency primary amenorrhoea;
hydroxylase Hormone replacement;
sexual infantilism
Address bone health
Hypocalciuria;
SLC12A3:
hypomagnesemia;
Gitelman thiazide-
AR hypotension; hypokalaemia; See table 17
syndrome (GS)±± sensitive NaCl-
hypocalciuria; alkalosis;
co-transporter
weakness & tetany
Onset in infancy
Isolated Hypomagnesaemia;
autosomal normal K+/Ca2+;
dominant hypo- normal/low urinary Ca2+/ KCNA1:
AD Mg2+ replacement
magnesaemia normal urinary Mg2+; Kv1.1
(IADHG) muscle cramps, weakness;
tetany; tremor; seizures
Onset in infancy
Low Mg2+; normal Ca2+; CLDN16:
High urinary Ca2+/Mg2+; claudin-16
Isolated nephrocalcinosis; stones; EGF:
recessive hypo- progressive CKD; epidermal
magnesaemia AR Mg2+ replacement
recurrent UTIs; polyuria, growth factor
(IRH) polydipsia; failure to thrive; CLDN19:
muscle cramps, weakness; claudin-19
tetany; tremor; seizures
Hypo-
Low Mg2+; Low Ca2+
magnesaemia TRPM6:
AR Tetany; muscle spasms; Mg2+ replacement
with secondary HOMG
developmental delay
hypocalcaemia

Collecting Duct (CD)
Glucocorticoid- Hyperaldosteronism;
CYP11B1- steroids: dexamethasone/
remediable low renin; hypertension;
AD CYP11B2 hydrocortisone/prednisolone
aldosteronism mild hypokalaemia;
chimera spironolactone/eplerenone
(GRA) risk of haemorrhagic stroke
Correction of acidosis and
hypokalaemia
Hyperchloraemia; mild Alkali therapy:
Distal renal hypokalaemia; mild acidosis; SLC4A1: Na+ & K+ bicarbonate/citrate;
AD late onset nephrolithiasis; Potassium citrate if
tubular acidosis anion
(AR) nephrocalcinosis; mineral hypokalaemia/calcium stones
(dRTA) Type 1 exchanger 1
bone loss (asymptomatic) Vit. D/Ca2+ supplementation
ADV7103 – alkali therapy at
clinical trial phase
Correction of acidosis and
Hyperchloraemia; ATP6V0A4: hypokalaemia
hypokalaemia; severe V-ATPase Alkali therapy:
Distal renal acidosis; growth failure; subunit A4 Na+ & K+ bicarbonate/citrate;
tubular acidosis vomiting/dehydration; ATP6V1B1: Potassium citrate if
(dRTA) Type 1 AR
progressive sensorineural V-ATPase hypokalaemia/calcium stones
with Deafness hearing loss; rickets; subunit B1 Vit. D/Ca2+ supplementation
nephrolithiasis MDT approach
Audiologist input
Seizures, Sensorineural
deafness, Ataxia, Mental
disability, Electrolyte
imbalance (SeSAME); Antiepileptic medication
SeSAME metabolic alkalosis; Electrolyte replacement
KCNJ10: Physical, educational and
syndrome AR hypomagnesaemia;
K+channel speech therapy, audiologist
(EAST syndrome) hypokalaemia
Epilepsy, Ataxia, input
Sensorineural deafness,
Tubulopathy (EAST)
SCNN1B:
Pseudoaldosteronism, low Reduce BP; normalise K+:
ENaC-β
renin, hypertension, Low Na+ diet
SCNN1G:
Liddle syndrome AD hypokalaemia, metabolic K+-sparing diuretics
ENaC-γ
alkalosis, arrhythmia; conventional
(gain-of-
constipation antihypertensives ineffective
function)
Pseudohypoaldosteronism
MLR1: Fluid balance
Pseudohypo- type 1, ↓Na+, ↑K+,
mineralo- Na+ supplementation
aldosteronism AD ↑aldosterone, ↑renin
corticoid K+ binding resins
Type 1a Neonatal vomiting and
receptor 1 Improves with age
dehydration
SCNN1A:
Pseudohypoaldosteronism ENaC-α Manage fluid balance;
type 1, ↓Na+, ↑K+, SCNN1B: high Na+ /low K+ diet;
Pseudohypo- ↑aldosterone, ↑renin ENaC-β K+ binding resins;
aldosteronism AR Severe neonatal vomiting and SCNN1G: Prostaglandin inhibitors;
Type 1b dehydration ENaC-γ Alkalizing agents;
Respiratory distress (loss of Thiazide diuretics
function)
WNK1:
Pseudohypo- Pseudohypoaldosteronism, Dietary Na+ restriction;
serine/
aldosteronism low renin; ↑K+; ↑Cl−; ; K+ binding resins;
threonine-
Type 2 AD metabolic acidosis; Prostaglandin inhibitors;
protein kinase
(PHA2; Gordon hypertension low/high Alkalizing agents;
WNK1
syndrome) aldosterone Thiazide diuretics
WNK4:
(continued)

serine/
threonine-
protein kinase
WNK4
AVPR2:
Nephrogenic AVP2 replace urinary H2O losses;
XD, Polyuria; polydipsia; receptor
diabetes thiazide diuretics;
AR hypernatraemia AQP2:
insipidus amiloride; low Na+ diet
aquaporin-2
Secondary Tubulopathy
Fanconi type tubular Alkali therapy:
dysfunction, Aminoaciduria, Na+ & K+ bicarbonate/citrate;
RTA, CKD, vit. D-resistant K+ & Ca2+ supplementation;
Lowe syndrome XR rickets Congenital Cataract, , OLRL1, PIB5PA oral carnitine;
hypotonia, motor oral PO4 & calcitriol;
developmental delay, KRT: kidney transplant;
intellectual disability, seizure control
Early Fanconi syndrome;
progressive CKD; ESKD <12yrs;
Eye involvement:
(photophobia, retinal
depigmentation, visual
impairment; hypothyroidism, CTNS:
portal hypertension, hepato- lysosomal
Cystinosis ±±± AR See table 18
splenomegaly, T2DM, muscle membrane
weakness, low testosterone; protein
incomplete pubertal
development;
encephalopathy; pyramidal
signs; cranial nerve palsies
may occur
Early treatment advocated to
Proteinuria, progressive CKD avoid kidney complications/
(FSGS, TIN); MELAS syndrome
Maternally- Sensorineural hearing loss; Symptomatic management;
inherited diabetes mellitus in adults oral antidiabetic agents +/-
MT-TL1;
diabetes and (seek maternal inheritance); insulin for T2DM;
Mt MT-TK;
deafness pigmentary retinopathy; hearing aids/cochlear
MT-TE
(MIDD) ptosis; implants;
cardiomyopathy; myopathy; Co-enzyme Q10
neuropsychiatric symptoms supplementation proposed to
treat mitochondrial defect
Abbreviations: AD Autosomal dominant, AR Autosomal recessive, FSGS Focal segmental glomerulosclerosis, Glu
Glucose, GS Gitelman syndrome, H2O Water, K+ Potassium, LMW Low molecular weight, Mg2+ Magnesium, MOI
Mode of inheritance, Mt Mitochondrial inheritance, Na+ Sodium, NaHCO3 Sodium bicarbonate, NaCl Sodium chloride,
PO4 Phosphate, PTH Parathyroid hormone, TIN Tubulo-interstitial nephritis, TmG Tubular maximum rate for glucose
transport, T2DM Type 2 diabetes mellitus, Vit. D Vitamin D, XD X-linked dominant, XR X-linked recessive
a
See Table 15.16
b
See Table 15.17
c
See Table 15.18
Table 15.16 Diagnosis & Management of X-linked hypophosphataemia (XLH)± [18]

X-Linked Hypophosphataemia (XLH) [18]
Clinical Presentation • X-linked dominant disorder caused by mutations in PHEX, encoding
fibroblast growth factor 23 (FGF23), a cell-surface-bound protein-cleavage
enzyme expressed in osteoblasts, osteocytes and teeth
• Commonest cause of inherited phosphate wasting
• Presentation with signs of rickets (children)/osteomalacia (adults) in
association with hypophosphataemia and renal PO4 wasting in absence of Vit.
D/Ca2+ deficiency
• Diagnosis confirmed by measuring fibroblast growth factor 23 (FGF23) levels
Genetic Diagnosis • Confirmation of genetic mutation in PHEX
• Reduce osteomalacia, and improve oral health
• Monitor serum Ca2+
• Conventional treatment: treat symptomatic adults with:
• active vitamin D (calcitriol),
• oral phosphorus (phosphate salts)
• Burosumab: recombinant human mAb against FGF23 approved to treat XLH
• if available - should be considered in adult XLH patients with:
• persistent bone and/or joint pain
• osteomalacia that limits daily activities
• pseudo-fractures
• osteomalacia-related fractures
• an insufficient response or refractory to conventional therapy
• should be discontinued if fasting serum PO4 level > upper limit of normal
[18]
• must not be given alongside conventional treatment when PO4 levels normal
pre-treatment
• must not be given in presence of advanced CKD [18]
Abbreviations: Ca2+ Calcium, CKD Chronic kidney disease, mAb Monoclonal antibody, PO4 Phosphate, Vit. D
Vitamin D;
±
refers to where XLH is referenced in other tables in the chapter
secondary kidney tubulopathies the genetic Gene identification has rendered this heteroge-
defect does not directly affect a tubular transport neous disease group of tubulopathies more acces-
or transport signalling protein, but rather non- sible to unequivocal diagnostics, and thereby to
specifically leads to damage of kidney tubular the promise of more refined management strate-
cells, and thereby to kidney tubular dysfunction. gies [3].
Table 15.17 Diagnosis & Management of Gitelman Syndrome (GS)±± [19]

Gitelman syndrome (GS)
Clinical Criteria for suspecting GS Features against a diagnosis of GS
Presentation • Usually detected during adolescence or • Use of thiazide diuretics/laxatives
adulthood. • AD family history of kidney disease
• Electrolytes: Chronic hypokalemia • Electrolytes: Hypokalemia absent (except in
(<3.5 mmol/l) with inappropriate renal CKD/ESKD)
potassium wasting (spot • Inconsistent hypokalemia in absence of
potassium:creatinine ratio >2.0 mmol/ substitutive therapy
mmol [>18 mmol/g]) • Metabolic alkalosis absent (unless coexisting
• Metabolic alkalosis bicarbonate loss/acid gain)
• Hypomagnesaemia (<0.7 mmol/L • Low plasma renin
[<1.70 mg/dL]) with inappropriate renal • Urine: Low urinary potassium excretion (spot
magnesium wasting (fractional excretion of potassium-creatinine ratio < 2.0 mmol/mmol
magnesium >4%) [<18 mmol/g]); Hypercalciuria
• High plasma renin • BP: Hypertension/clinically increased
• Urine: Hypocalciuria (spot calcium- extracellular fluid volume
creatinine ratio < 0.2 mmol/mmol • Ultrasound: nephrocalcinosis, nephrolithiasis,
[<0.07 mg/mg]) in adults unilateral/cystic kidneys
• Fractional excretion of chloride >0.5% • Prenatal history of polyhydramnios,
• BP: Low/low-normal hyperechogenic kidneys
Ultrasound: Normal kidneys • Presentation before age 3 years
Genetic Criteria for establishing a diagnosis of GS
Diagnosis • Identification of biallelic inactivating mutations in SLC12A3, encoding thiazide-sensitive
sodium-chloride cotransporter (NCC)
• Hydrochlorothiazide testing no longer recommended as a diagnostic tool in GS: when used
diagnostically to differentiate from Bartter syndrome, there is a risk of acute volume depletion
in subjects with loop of Henle defect
• Unless specific manifestations (e.g., significant proteinuria) are encountered, kidney biopsy is
not necessary for the diagnosis of GS [19]
• NGS–based gene panel to include differentials for GS: SLC12A3; CLCNKB; HNF1B
• If only a single variant identified by NGS panel sequencing, analysis should be complemented
with a test for a deletion on the other allele [19]

Gitelman syndrome (GS)
Management Individualised lifelong oral NaCl, K & Mg supplementation:
• GS is caused by a primary defect in a NaCl cotransporter, and is broadly managed by a liberal NaCl intake
together with oral Mg and K supplements:
• In hypomagnesaemia, Mg supplementation should occur first: Mg repletion facilitates K repletion, reducing
risk of tetany/other complications
• Cornerstone of preventing chondrocalcinosis is Mg supplementation
• No evidence correlating severity of blood levels with symptom intensity
Monitoring for side effects of supplementation
• Target K level around 3.0 mmol/L
• Target Mg level 0.6 mmol/L (1.46 mg/dL)
• Achieving target electrolyte levels sometimes challenging
• Supplementation with large doses may result in serious side effects: gastric ulcers, vomiting, diarrhoea with
worsening electrolyte levels
• An individual balance between improvement in blood values and side effects should be established
• Realistic target values may be lower for some patients and may also change with time
Drugs to be avoided/used with caution:
• The following drug groups to be avoided/used with caution in GS:
• Drugs slowing sinus rhythm/affecting QT interval (e.g. negative chronotropic drugs)
• Drugs potentially exacerbating hypomagnesaemia (e.g. PPIs, gentamicin, antiviral drugs), acetazolamide
Intravenous potassium chloride (KCl)
• May be necessary when patient cannot take oral drugs/when the K deficit is very severe, causing cardiac
arrhythmia/quadriplegia/respiratory failure/rhabdomyolysis
Intravenous Magnesium Chloride (MgCl2)
• Intravenous Mg infusion should be reserved for patients presenting with acute, severe complications of
hypomagnesemia (e.g., tetany, cardiac arrhythmias), or in cases of digestive intolerance to oral supplements
Potassium-sparing diuretics
– Amiloride, spironolactone, potassium canrenoate, and eplerenone can increase serum potassium levels
resistant to supplements and treat magnesium depletion that is worsened by elevated aldosterone levels
– Use of spironolactone complicated by antiandrogenic effects, which are difficult in adolescents and young adults
– Eplerenone is a selective aldosterone antagonist, with fewer antiandrogenic side-effects K-sparing diuretics
compound renal salt wasting, so should be started cautiously to avoid hypotension, and concomitant salt
supplementation should be considered
RAAS blockade
• The use of RAAS blockade has been occasionally reported in the treatment of GS: they may also aggravate
renal sodium wasting and increase risk of symptomatic hypovolemia. RAAS inhibitors (ACEi/ARBs) should
be stopped in cases of acute, salt-losing complications, e.g. vomiting/diarrhoea
NSAIDs
Prostaglandin synthase inhibitors
• Prostaglandin synthase inhibitors such as indomethacin are rarely used in GS, because urinary prostaglandin
E2 levels in GS are usually normal
• Refractory hypokalemia has also been treated with the specific COX-2 inhibitor rofecoxib, but the use of this
drug is limited by its long-term cardiovascular effects
Analgesia for chondrocalcinosis
• Both oral NSAIDs and low-dose oral colchicine are effective systemic treatments for acute chondrocalcinosis
• NSAIDs must be used with caution in GS due to risk of AKI;
• Colchicine treatment can increase the laxative effect of oral magnesium supplementation
• Intra-articular corticosteroids may be considered in patients in whom other drugs are contraindicated
Genetic Counselling
• Genetic counselling should be offered to any patient with GS and to parents with a young child suffering from
the disease
• Could discuss testing of parents, siblings and partner
• Prenatal diagnosis and preimplantation genetic diagnosis are technically feasible when 2 pathogenic SLC12A3
mutations have been identified, although the prognosis is good for most GS patients: In very severe cases of
GS, the possible use of these predictive tests can be discussed
Considerations in Pregnancy
• Aggravation of hypokalaemia and hypomagnesaemia during pregnancy necessitates early institution of a joint
management plan and adaptations in Na/Mg/K supplementation
• ACEi/ARB must be stopped during pregnancy due to significant foetal risk
• Monitoring of plasma electrolyte levels advised during labour
• After delivery, the treatment of the mother may return to baseline supplementation and follow-up
Abbreviations: ACEi Angiotensin converting enzyme inhibitor, AD Autosomal dominant, AR Autosomal recessive, ARB
Angiotensin receptor blocker, BP Blood pressure, CKD Chronic kidney disease, ESKD End stage kidney disease, K
Potassium, Mg Magnesium. NaCl Sodium chloride, NGS Next generation sequencing, PPIs Proton pump inhibitors
±±
is shorthand for where Gitelman Syndrome (GS) is referenced in other tables in the chapter
Table 15.18 Diagnosis & Management of Cystinosis±±± [20]

Cystinosis [20]
Clinical Presentation • Cystinosis is an autosomal recessive lysosomal storage disease caused by mutations
in the CTNS gene, leading to intralysosomal accumulation of cystine crystals, which
damages several organs, including the kidneys
• Nephropathic infantile cystinosis is commonest and most severe variant
• Symptoms of multiorgan involvement may be mild to severe, depending on patient’s
age at diagnosis, the age when treatment was instituted, and genetic factors: Patients
usually present during the first year of life with polyuria, polydipsia, dehydration,
metabolic acidosis (normal anion gap hyperchloremic acidosis), hypophosphatemic
rickets, failure to thrive, and laboratory findings consistent with Fanconi syndrome.
If untreated, ESKD develops by age 7–10 years
• Late-onset (intermediate) nephropathic cystinosis is more indolent: age at
manifestation is most commonly in early adolescence. Symptoms usually restricted
to kidneys: (less severe form of Fanconi syndrome, proteinuria) and eyes
(photophobia). Disease progression is slower: ESKD occurs after age 15 years
Genetic Diagnosis • Intracellular cystine concentrations (in white blood cells [WBC] or selected WBC
types) are used clinically as the only available biomarker for diagnosis, and for
gauging therapeutic success at the reduction in intracellular cystine accumulation.
Monitoring therapeutic response in this manner is associated with better long-term
outcomes, despite inconsistencies between laboratories [20]
• Bi-allelic mutations in the CTNS gene confirms the genetic diagnosis
• Early oral administration of cysteamine, which reverses cystine accumulation via a
newly described PQLC2 heptahelical protein substantially delays onset of ESKD,
and the development of other complications [20]
• Despite substantial improvement in prognosis due to cystine-depleting therapy with
cysteamine, no cure of the disease is currently available [1]
• A pre-emptive kidney transplant remains the best choice of KRT: widely accepted
that there is no risk of recurrence, since the genetic defect is not transferred with the
allograft
• Cysteamine treatment is usually withdrawn for kidney transplantation, but the delay
in resuming treatment should be limited to a few days: it is strongly recommended
that there be a continuation of cysteamine treatment in patients treated by dialysis or
transplantation [20]
Primary Hypogonadism in male patients
• Testosterone-replacement therapy allows pubertal development, but doesn’t prevent
infertility
Pubertal delay in female patients
• Female patients with cystinosis are fertile.
• Protective effect on gonads from early cysteamine treatment has been shown.
• Successful pregnancies have been described
• Pre-conception counselling should be offered to all women contemplating
pregnancy
• Cysteamine therapy should be stopped during pregnancy: the optimal time for
stopping cysteamine should be part of the preconception counselling
Cystinosis Myopathy
• Continue cystine reduction therapy
• Muscle testing, electromyogram, and changes in pulmonary function should be used
as endpoints for therapeutic intervention studies
• Physiotherapy and exercise may be useful adjunctive therapies
is shorthand for where Cystinosis is referred to elsewhere in other tables in the chapter
±±±
Nephrolithiasis ment of nephrolithiasis in Table 15.20; and the

diagnosis and management of Cystinuria in Table
Genetic causes of kidney stones (nephrolithiasis) 15.21, and that of Primary Hyperoxaluria Type 1
are described in Table 15.19, the general manage- in Table 15.22.
Table 15.19 Nephrolithiasis [3]

Characteristic signs Gene symbol(s):
Genetic Disorder MOI Management
and features Gene product(s)
Aminoaciduria, cystine SLC3A1: amino acid

calculi, recurrent UTI, transporter 1
Cystinuria^ AR haematuria, dysuria (Type A) See table 15.21
Mixed AB genotype SLC7A9: CSNU3
rarely develop stones (Type B)
Fanconi syndrome with
Increased fluid intake,
CKD (men);
CLCN5: diuretics, high citrate
Dent’s disease XR Hypercalciuria;
renal Cl-Channel diet,
Radiopaque Ca2+
refer for bone studies
stones; rickets
Oxalate
nephrolithiasis;
metabolic acidosis;
failure to thrive; AGXT :
Primary hyperoxaluria
AR nephrocalcinosis; Ala-glyoxylate See table 15.22
type 1(PH1)^^
ESKD; hypothyroidism; aminotransferase
cardiac failure;
myopathy
Oxalate nephrolithiasis
metabolic acidosis; High fluid intake
failure to thrive; Urinary alkalinization
Primary hyperoxaluria nephrocalcinosis; GRHPR: NO rationale for
AR
type 2 (PH2) ESKD; hypothyroidism; glyoxylate reductase pyridoxine (Type 2);
cardiac failure; KRT
myopathy
Oxalate nephrolithiasis
metabolic acidosis;
failure to thrive; HOGA1: High fluid intake
Primary hyperoxaluria nephrocalcinosis; 4-hydroxy-2- Urinary alkalinization
AR oxoglutarate vegetarian diet (Type 3)
type 3 (PH3) ESKD; hypothyroidism;
cardiac failure; aldolase 1 KRT
myopathy
APRT: Allopurinol
Adenine- Urate nephrolithiasis;
adenine High fluid intake
phosphoribosyl- AR radiolucent stones;
phosphoribosyl Low purine diet
transferase deficiency DHA nephropathy
transferase Monitor crystalluria
xanthine calculi;
failure to thrive;
gross/microscopic High fluid intake
haematuria; pyuria; XDH: Low purine diet
Xanthinuria AR renal colic; UTI; xanthine
arthropathy; dehydrogenase Surgical care for
myopathy; low serum xanthine stones - ESWL
urate
High fluid intake
Haematuria; medullary Diet modification
nephrocalcinosis; GDNF: Thiazide diuretics (Ca2+
Medullary Sponge nephrolithiasis; stones), allopurinol
(AD) Glial-derived
Kidney (MSK) urolithiasis; UTI; (urate stones), Ca2+
neurotrophic factor
metabolic acidosis citrate (oxalate stones)
Antibiotic therapy
(continued)

Stone management –
ESWL
Surveillance for Wilms
Tumour in children
High fluid intake
Ca2+ nephrolithiasis,
ADCY10 : Diet modification
Familial Hypercalciuria AD nephrocalcinosis,
Adenylate cyclase 10 Allopurinol
osteoporosis
Thiazide diuretics
High fluid intake
Diet modification –
SLC26A1: reduce oxalate rich
Calcium Oxalate kidney Oxalate nephrolithiasis
AR Sulphate anion foods, reduce Na+
stones kidney colic; UTIs
transporter 1 Surgical management –
ESWL
Abbreviations: ESWL Extracorporeal shock wave lithotripsy, UTI Urinary tract infection
^
See Table 15.21
^^
See Table 15.22
Table 15.20 General diagnosis & management of nephrolithiasis [21, 22]
(continued)

Table 15.21 Diagnosis & Management of Cystinuria^ [23]

Cystinuria [23]
Clinical • AR condition: high urinary cystine and dibasic amino acid excretion leads to formation
Presentation of cystine stones due to low solubility of cystine at normal urinary pH
• Detection of hyperechoic colon during routine ultrasound before 36 weeks’ gestation
may suggest diagnosis of cystinuria, with a high PPV
• In most patients, first stone detection occurs during childhood or adolescence
• Diagnosis of cystinuria can be made by kidney stone analysis, observation of cystine
crystals in urinary sediment, or detection of an abnormal excretion of cystine and dibasic
amino acids in urine in adults and children [23]
Genetic Diagnosis • Type A: SLC3A1: amino acid transporter 1
• Type B: SLC7A9: CSNU3 amino acid transporter
• Genetic analysis should be performed in patients with cystinuria, allowing diagnostic
confirmation, disease classification, and counselling of other family members, (although
no strong genotype-phenotype correlations yet demonstrated)
• Patients with cystinuria are at higher risk of CKD and early onset hypertension
• Conservative treatment is based on a stepwise strategy, addressing hydration, diet, and
urinary alkalinization as basic measures, specific treatment of kidney tract stones, and
thiol derivatives in refractory cases
Specific measures
• Hydration: Increased Fluid intake to guarantee a urine output large enough to maintain
a cystine concentration of <250 mg/L
• Diet: Dietary restriction of methionine and sodium
• Urinary alkalization: oral potassium citrate – monitor urinary pH
• Managing kidney tract stones:
• Patients with cystinuria and ureteral stones who are well, with no infection or kidney
impairment can be observed for up to 4 weeks for stone passage
• Ongoing pain, kidney impairment, and low chance of spontaneous passage are
indications for prompt treatment of stones
• An NSAID should be the first drug of choice in the absence of contraindications.
• Decompression (stent/nephrostomy) should be undertaken in patients with infected or
obstructed kidneys
• Due to recurrent nature of cystine stones, complete stone clearance should be achieved
whenever possible
• Thiol derivatives: (alpha-mercaptopropionylglycine (Tiopronin) and D-penicillamine)
effective in reducing free urine cystine levels: monitor complete blood cell count and
urinary protein excretion regularly
Abbreviations: CKD Chronic kidney disease, NSAIDs Non-steroidal anti-inflammatory drugs, PPV Positive predictive
value
Table 15.22 Diagnosis & Management of Primary Hyperoxaluria Type 1^^ [24]
Primary Hyperoxaluria Type 1 [24]
Clinical • Rare autosomal recessive inborn error of glyoxylate metabolism, caused by deficiency of the
Presentation liver-specific enzyme alanine:glyoxylate aminotransferase
• Results in overproduction and excessive urinary excretion of oxalate, causing recurrent
urolithiasis and nephrocalcinosis
Genetic • Genetic tests for mutations in AGXT recommended in subjects with phenotypic
Diagnosis characteristics of PH1
• Mutation analysis should be extended to siblings and parents, offering prenatal diagnosis
using mutation analysis to parents of an affected child [24]
• Early initiation of conservative treatment
• High Fluid intake (at least 3 L/m2 per 24 h)
• Vitamin B6 (pyroxidine) in patients with proven PH1 aiming to decrease urine oxalate
excretion
• Calcium oxalate crystallization inhibition by use of alkalization with oral potassium citrate
aims at maintaining renal function [24]
• Conservative measures should be initiated as soon as investigations are completed and while
renal function is maintained.
• Once ESKD established, pyridoxine is the only specific treatment that should be pursued.
These measures apply to all types of PH, with the exception of pyridoxine, which is specific
to PH1 [24].
• Endoscopic removal is recommended as preferential strategy to manage urolithiasis in
patients who require intervention.
• Avoiding any form of dialysis unless absolutely necessary is recommended and to consider
pre-emptive transplantation in PH1 patients with progressive CKD
• Where pre-emptive transplantation is not possible high efficacy dialysis is recommended as
conventional dialysis is unable to remove sufficient quantities of oxalate proportionate to the
continuous daily production; avoid loop diuretics post transplantation; dialyse pre-emptively
immediately post transplantation to help clear residual oxalate load [24]
• In ESKD due to PH1, simultaneous liver-kidney transplantation should be considered
^^is shorthand referring to where PH1 is referred to back in tables earlier in the chapter
ongenital Abnormalities of Kidney

C Hereditary Systemic Amyloidosis
and Urinary Tract (CAKUT)
Genetic causes of Hereditary Systemic
CAKUT are a group of disorders of characterised Amyloidosis are described in Table 15.24.
by anatomical abnormalities the kidneys, ureter,
urine bladder and urethra present from birth
(Table 15.23).
Table 15.23 Congenital abnormalities of the kidney and urinary tract CAKUT [3]
(continued)

(continued)
Abbreviations: ACEi Angiotensing converting enzyme inhibitor, AD Autosomal dominant, AFP Alpha-fetoprotein lev-
els, AR Autosomal recessive, ARB Angiotensin receptor blocker, BOR Branchio-oto-renal syndrome, CKD Chronic kid-
ney disease, ESKD End stage kidney disease, FSGS Focal and segmental glomerulosclerosis, MOI Mode of inheritance,
PUJO Pelvi-ureteric junction obstruction, RAS Renal artery stenosis, US Ultrasound, VUR Vesico-ureteric reflux
Table 15.24 Hereditary Systemic Amyloidosis

Conclusions our understanding of these pathways [1].

Additionally, we recognise that an individual’s
Returning to the patient from the beginning of the carrier status for certain genetic kidney disorders
chapter, who presents with cystic kidney disease, may prove important beyond genetic counsel-
and an autosomal dominant inheritance pattern of ling: with potentially important clinical implica-
‘CKD’: It would be invaluable to supplement the tions for carriers themselves: where heterozygous
rather scant phenotypic information available carriers of X-linked recessive disorders are usu-
from the history with a precise cause of CKD in ally asymptomatic or mildly affected, in some
his father and paternal grandmother, as well as heterozygotes, a more severe disease outcome is
the presence or absence of other discriminating noted, notably in Alport syndrome and Fabry dis-
features: these might include the size of his cystic ease. As such, carrier status for certain conditions
kidneys, presence or absence of cysts in other may yet have important implications, for exam-
organs, characteristic skin rashes, epilepsy, learn- ple in selecting living-related kidney transplant
ing difficulties, or a history of type 2 diabetes donors [1].
mellitus, ESKD, stroke or sudden death in the There are many exciting opportunities offered
family. Without significant further information, it by NGS: lowering costs and the lead-time for
would seem reasonable to counsel him appropri- results from high-throughput sequencing; along-
ately about the benefits and risks (including of side the carefully designed, internationally col-
not getting a definitive diagnosis) - of undertak- laborative bioinformatic platforms, such as the
ing a genetic sequencing panel, focused on candi- European Rare Kidney Disease Network
date genes associated with cystic kidney disease (ERKNet). Other drives such as the Human
(Table 15.5). Phenotype Ontology website, and the Online
Despite considerable advances in understand- Mendelian Inheritance in Man “OMIM” cata-
ing the molecular cause of many genetic kidney logue of Human Genes and Genetic Disorders
diseases, the aetiologies for most remain help to continuously refine genomic datasets in
unsolved. That said, even where the genetic cause clarifying molecular pathways associated with
is well-defined, such as in Alport and Bartter syn- particular phenotypes, and hence driving the
dromes, genetic testing is not commonplace – identification of novel therapeutic targets for rare
influenced by the associated high costs, long kidney diseases. We must acknowledge the
turnaround times, a preconception that the reverse argument too – that certain iterations of
genetic diagnosis will not alter clinical manage- NGS applied in an individual can generate an
ment, insufficient genetic knowledge amongst enormous amount of incidental data, the thera-
clinicians, and differences in access to genetic peutic, moral and ethical implications of inter-
testing, amongst other factors [1]. preting this data are yet to be explored [1].
As the boundaries of our knowledge of genetic Taking the global perspective, genetic testing
kidney disease move inexorably forward, we is not equally available in all countries equitably
appreciate ever more fascinating peculiarities— to screen for genetic kidney diseases - indeed
each with important clinical applications: a num- there may be unequal access to genetic testing
ber of genetic kidney diseases previously between different areas within the same country.
considered part of a single disorders have been Designing pathways for genetic testing that facil-
shown to be genetically heterogeneous, with itate timely genetic testing for patients with sus-
mutations in different genes along the same bio- pected genetic kidney disease, that is equally
logical pathways, giving rise to similar clinical, affordable and accessible in less well-resourced
biochemical, and histopathological features, regions and countries alike, is arguably as impor-
which simultaneously reinforces - and develops -
tant as the continuing drive to develop novel ther- A subsequent ultrasound scan reveals multi-
apies for these diseases. ple cysts on both kidneys. His blood tests
reveal his serum creatinine is 70 μmol/L
(eGFR >90 mL/min/1.73 m2). He has no his-
Questions tory of diabetes mellitus, no skin rashes, and
no other medical problems of note.
1. An 18 year old gentleman of mixed heritage His father and paternal grandmother were both
is been found to have isolated microscopic said to have had chronic kidney disease, with
haematuria on dipstick, with a normal ultra- ‘lots of cysts’ on their kidneys, but there is no
sound scan. His serum creatinine is history in the family of progression to ESKD.
60 μmol/L, (eGFR >90 mL/min/1.73 m2). Which of the following is least likely to be
His mother – who was born in China, also included on the list of differential
has dipstick haematuria, as does his maternal diagnoses?
grandmother. His father, from India, does
not. There is no family history of deafness, A. Autosomal dominant polycystic kidney
visual disturbance or ESKD requiring KRT. disease (ADPKD)
Genetic testing has identified that he is hetero- B. Tuberous sclerosis complex (TSC)
zygous for a COL4A3 mutation. What should C. Autosomal dominant tubulointerstitial
the patient be advised? kidney disease (ADTKD)
D. Renal cysts and diabetes (RCAD)
A. The diagnosis is consistent with Alport syndrome
disease E. Alport syndrome
B. The diagnosis is consistent with IgA
nephropathy (IgAN) Answer: E—Whilst each of the diseases listed
C. The diagnosis is consistent with thin can display an AD inheritance pattern, as
basement nephropathy (TBMN) illustrated in the patient’s family history,
D. He is likely to progress to ESKD Alport syndrome is more typically X-linked
E. He is likely to develop deafness recessive, and not characterised by cystic
kidney disease, but rather by microscopic
Answer: C—The patient has been shown to be haematuria, progressive proteinuria, and an
heterozygous for a COL4A3 mutation. This association with hearing loss.
is consistent with TBMN, with an AD inheri- 3. A 22-year-old female medical student has
tance pattern of a phenotype demonstrating found to have multiple cysts on both kidneys
isolated haematuria. To confirm this, genetic on a screening ultrasound scan. She had been
testing should be undertaken on both parents. advised to do so by her father, a doctor, who
As a carrier of a gene associated with AR has recently been diagnosed with autosomal
Alport syndrome, there is a risk of his off- dominant polycystic kidney disease, and has
spring developing Alport syndrome, depen- had to start haemodialysis. He has been
dent on any prospective partner’s carrier found to have a pathogenic PKD1 mutation.
status, and the patient should be signposted To her knowledge, her paternal grandmother
toward genetic counselling when the time is had a kidney transplant some years ago, but
appropriate. she doesn’t know the cause of her kidney
2. A 29-year-old male banker is found to have disease.
dipstick haematuria, but no significant pro- On examination, her blood pressure is
teinuria on his routine medical examination. 120/70 mmHg, and her pulse 56 beats/min-
ute. Her cardiac, chest, abdominal and neu- 4. A 24 year old female airport worker – origi-
rological examinations are all unremarkable. nally from Ghana - presents to her primary
Her blood tests reveal a serum creatinine of care practitioner with headaches and mild
56 μmol/L (eGFR >90 mL/min/1.73 m2). abdominal discomfort, which is affecting her
There is no history of diabetes mellitus, no memory and concentration. Her urinalysis
skin rashes, and no other medical problems revealed dipstick haematuria. A subsequent
of note. abdominal ultrasound scan reveals several
What is the next most appropriate step in her bilateral solid kidney masses, associated
management? with several cysts. Blood tests reveal a serum
creatinine of 80 μmol/L (eGFR >90 mL/
A. Drink 1–1.5 L of fluid per day min/1.73 m2).
B. Gene sequencing panel for cystic kidney She experienced a normal childhood in Ghana,
disease and is noted to have a facial rash, which has
C. Cross-sectional imaging (CT/MRI) become more extensive during adolescent
D. Commence Tolvaptan immediately years, and painful nodules under the nails of
E. Counsel her about obtaining a pre- her first and fourth fingers of her right hand.
implantation genetic diagnosis To her knowledge, there is no family history
of any similar condition.
Answer: C—She is highly likely to have inher- What is the most likely diagnosis?
ited the pathogenic PKD1 mutation from her
father, and she is also highly likely to prog- A. Neurofibromatosis Type 1 (NF1)
ress to ESKD, as have her father and paternal B. Von Hippel Lindau (VHL) Disease
grandmother. Obtaining baseline cross-sec- C. Tuberous sclerosis complex (TSC)
tional imaging to establish her baseline total D. Lennox-Gastaut syndrome (LGS)
kidney volume (TKV) can serve to provide a E. Hereditary leiomyomas and renal cell
marker to facilitate prognostication, as well carcinoma (HLRCC)
as a baseline to evaluate the response to pro-
spective Tolvaptan (or other) therapy. She Answer: C The patient’s physical features are
should be advised to increase her water most in keeping with bilateral kidney angio-
intake (likely to much more than 2 L per myolipomas (AMLs) and associated cysts,
day), alongside close monitoring of her associated with facial angiofibromas, and
blood pressure. Confirming her genetic diag- subungual fibromas. These would be suffi-
nosis by sequencing PKD1 to confirm inheri- cient to meet the criteria for a definite diag-
tance of the pathogenic PKD1 mutation nosis of TSC (Table 11). Whilst her
would facilitate discussion about her options headaches, that may be affecting her memory
with regard to having offspring in future, and and concentration may be a non-specific pre-
should form part of (but not the main focus sentation, the clinical context should never-
of) the discussion around genetic testing. theless prompt urgent cross-sectional brain
Tolvaptan therapy would be indicated where imaging to exclude significant mass lesions,
a patient has, or is at risk of rapidly progress- such as an obstructing subependymal giant
ing, CKD stages 1–3 in adult ADPKD cell astrocytoma (SEGA), causing hydro-
patients aged <50 years. Whilst she is cer- cephalus, which may necessitate urgent neu-
tainly at risk of progressing, in the clinical rosurgical intervention, and subsequent
context, it would be sensible to obtain base- consideration of mTOR inhibitor therapy.
line cross-sectional imaging first. There should be further consideration of the
possibility of an underlying seizure disorder. Answer: D All of the above differentials are
The other differentials on the list are associ- characterised by deafness, often associated
ated with skin lesions (NF1), kidney masses with kidney dysfunction, and may all present
(HLRCC, VHL), and Lennox-Gastaut syn- with an AD inheritance pattern. Whilst
drome (LGS) is a rare and severe kind of epi- Alport syndrome would be the commonest
lepsy that starts in childhood. cause, the presence of pre-auricular pits and
5. A 26-year-old male is referred as an emer- a neck lesion – consistent with a branchial
gency to the kidney service with a plasma fistula – makes BOR the more likely diagno-
creatinine of 1235 μmol/L (eGFR <5 mL/ sis in this context. Genetic testing is war-
min/1.73m2). He attended his primary care ranted to sequence the EYA, SIX1 and SIX5,
doctor with a 3-week history of oral thrush, although a panel approach excluding other
nausea, weight loss, nocturia and pruritus. causes of deafness and kidney dysfunction
He does not complain of visual problems, may be more appropriate.
rash or arthralgia and is not taking any medi- 6. A 24 year old male army recruit presents with
cations. His hearing has been impaired since complaints of weakness of the right lower
birth, to the point that he has required hear- limb of two months’ duration. Neurological
ing aids from the age of 11. His mother, evaluation determines a clinical impression
maternal grandfather, maternal aunt and of a compressive myelopathy at cervical ver-
uncle, and a brother, are also deaf. His mater- tebral levels C6–7. MRI of the brain and
nal aunt was known to have a moderate kid- spine reveals a predominantly cystic mass in
ney impairment. On examination, his blood the left cerebellar hemisphere, with enhanc-
pressure is 168/97 mmHg, his chest was ing intramedullary mass lesions, consistent
clear and abdominal examination unremark- with cerebellar and spinal haemangioblasto-
able. He is noted to have pre-auricular pits, mas. The patient is further investigated with
and a raised skin lesion over his neck. an abdominal ultrasound, which reveals mul-
Urinalysis demonstrates proteinuria 4+ and tiple simple cortical cysts in both kidneys,
haematuria 3+; urine protein:creatinine ratio with some solid components. The liver, pan-
is 560 mg/mmol. Blood tests show a haemo- creas, spleen and adrenals are otherwise nor-
globin of 72 g/L, MCV 90.6 fL, platelets mal. There is no history of familial
243 × 109 g/L, potassium 5.9 mmol/L, urea involvement. In view of the imaging findings,
47.4 mmol/L and creatinine 1235 μmol/L. His a clinical diagnosis of VHL disease is made.
serum albumin is 40 g/L, corrected serum What should be the next investigation?
calcium 1.97 mmol/L, phosphate
1.96 mmol/L and parathyroid hormone level A. MRI scan of the abdomen
64.0 pmol/L. Haematinic levels are normal. B. CT scan of the chest
His autoimmune screen shows no abnormal- C. Genetic sequencing of VHL
ity. Abdominal ultrasound demonstrates that D. Genetic sequencing of SDH, FH, TSC
both kidneys are <8 cm in bipolar length. and VHL
What is the most likely diagnosis? E. Brain biopsy
A. Alport syndrome Answer: A Whilst sequencing VHL would con-

B. Epstein syndrome firm the genetic diagnosis, it would not
C. Fechtner syndrome immediately alter his management: the first
D. Branchio-oto-renal syndrome (BOR) clinical priority should be to obtain cross-
E. Familial hypo/hyperparathyroidism sectional imaging of the abdomen to further
(HDR) elucidate the ultrasound findings, in particu-
lar the solid elements to the mass lesions on min, and examination of all other systems is
his kidneys, as there is a significant risk of normal. Urine microscopy shows 50
associated malignancy in the kidneys, as white cells/high power field, urine
well as the pancreas, and phaeochromocyto- protein:creatinine ratio was 105 mg/mol, and
mas, which should be followed with an her serum creatinine was 150 μmol/L.
appropriate multi-disciplinary team discus- What is the most likely genetic defect in the
sion about appropriate further treatment. family?
7. A 45 year old Caucasian man presents with a
two year history of burning sensation is his A. Cystinosis
hands and feet, dry skin, palpitations and pro- B. Fanconi disease
teinuria. On examination he is tall, his pulse is C. Juvenile nephronophthisis
95 beats/min, with a forceful cardiac apex D. UMOD mutation
beat and a normal neurological examination. E. Tuberous sclerosis complex (TSC)
Investigations show a serum creatinine of
87 μmol/L, haemoglobin 122 g/L, normal Answer: D With minimal proteinuria, leukocy-
liver function tests, a fasting glucose of turia, CKD and a strong family history, a
5.4 mmol/L, and a urine protein:creatinine familial form of tubulointerstitial disease is
ratio of 330 mg/mol. His kidney ultrasound the most likely diagnosis
and chest X-ray are normal, and his echocar- 9. A 54 year old lady presents to the medical
diogram demonstrates left ventricular intaking service with intermittent nausea,
hypertrophy. vomiting, muscle cramps and weakness. On
What is the most likely cause of his symptoms examination, her blood pressure is
and proteinuria? 110/70 mmHg, and her pulse 90 beats per
minute. Her chest, abdomen and cardiovas-
A. Apolipoprotein deficiency cular system examinations are normal; she
B. Alpha-galactosidase deficiency has proximal muscle weakness, but her
C. Autosomal dominant tubulointerstitial remaining neurological exam is normal. Her
nephritis blood tests at presentation are:
D. Amyloidosis Sodium: 139 mmol/L
E. Diabetes mellitus Potassium: 2.1 mmol/L
Urea: 5.1 mmol/L
Answer B: His presentation with acroparaes- Creatinine: 54 μmol/L
thesia, hypohydrosis, LVH and proteinuria in Urine microscopy: normal
a 45 year old male are suggestive of Fabry Urine dipstick: normal
disease (alpha-galactosidase deficiency). Urinary potassium: 60 mmol/L
8. A 34 year old female presents with an inci- What is the most likely cause of her
dental finding of proteinuria and a raised hypokalaemia?
serum creatinine following living kidney
donation 5 years ago. Her mother—the kid- A. Low potassium diet
ney allograft recipient -had been diagnosed B. Lower Gastrointestinal tract loss of
with end stage kidney disease of unknown potassium
cause, and had presented with minimal pro- C. Movement of potassium from plasma to
teinuria and a normal blood pressure. Her cells
uncle also received a kidney transplant D. Renal tubular defect
5 years ago. On examination her blood pres- E. Upper Gastrointestinal loss of potassium
sure is 125/68 mmHg, her pulse 68 beats/
Answer: D With a high urinary potassium, the another institution had been reported as show-
most likely cause of her hypokalaemia is ing ‘chronic glomerulonephritis’.
renal potassium loss The nephrologist noticed that the patient looked
10. A 54 year old lady presents to the medical at him intently during the consultation,
intaking service with intermittent nausea, which led to a sense of unease. At the end of
vomiting, muscle cramps and weakness. On the consultation the patient mentioned that
examination, her blood pressure is for some time her eyesight had been worry-
110/70 mmHg, and her pulse 90 beats/min. ing her. Haemoglobin 148 g/L, creatinine
Her chest, abdomen and cardiovascular sys- 186 μmol/L (we should state mg/dL in
tem examinations are normal. She has proxi- brackets too), albumin 40 g/L, urine protein
mal muscle weakness, but her remaining 1.2 g/24 h, Urine: RBC 60/μL, WBC <5/μL,
neurological exam is normal. Her blood tests Culture sterile. She was referred to the oph-
at presentation are: thalmologist for further assessment.
Sodium: 139 mmol/L In a chance meeting between the ophthalmolo-
Potassium: 2.1 mmol/L gist and nephrologist the following week, the
Urea: 5.1 mmol/L former was triumphant: “I’ve made both an
Creatinine: 54 μmol/L important ophthalmological diagnosis, and
Urine microscopy: normal made your diagnosis for you!” What is the
Urine dipstick: normal most likely diagnosis?
Urinary potassium: 60 mmol/L
She recalls that her brother, and a maternal A. Chronic glomerulonephritis
cousin have had ‘problems with their potas- B. Alport syndrome [unspecified]
sium’. Which of the following is the most C. Alport syndrome with anterior lenticonus
likely cause of her hypokalaemia? and hearing defect
D. IgA nephropathy
A. Bartter syndrome E. Alport syndrome with hearing defect
B. Gitelman syndrome
C. Liddle syndrome Answer: C Alport syndrome with anterior lenti-
D. Apparent mineralocorticoid excess conus and hearing defect.
E. Glucocorticoid remediable hypertension
A. Chronic glomerulonephritis --- Incorrect ---
Answer: B In the setting of hypokalaemia, and Answer not sufficiently focused.
notably a normal/low blood pressure - along- B. Alport syndrome [unspecified] ---
side proven excessive renal potassium wast- Incorrect --- Can be more specific.
ing, and without obvious other causes of C. Alport syndrome with anterior lenticonus
renal or GI potassium losses such as diuretics and hearing defect --- Correct ---
or laxatives, as well as a suggestive family Deafness meant that patient had to look
history of problems with potassium metabo- carefully at the doctor’s mouth when he
lism, consistent with an AR inheritance pat- was speaking. Her recent visual blurring
tern, Gitelman syndrome is the most likely of added to her difficulties. The anterior len-
the options. ticonus of Alport’s syndrome typically
11. A 20-year old Gujarati woman presented to presents at the age of 20.
Renal Outpatients. The referral letter stated D. IgA nephropathy -- Incorrect ---
that she had recently moved house and wanted Insufficient information for this option.
a review of her renal condition. It also men- E. Alport syndrome with hearing defect ---
tioned that 2–3 years earlier, a renal biopsy at Incorrect --- Less focused than Option C.
Test your learning and check your understand- als. J Am Soc Nephrol. 2015;26(1):160–72. https://
doi.org/10.1681/ASN.2013101138. Epub 2014 Jun
ing of this book’s contents: use the “Springer 5.
Nature Flashcards” app to access questions 10. Guay-Woodford LM, Braun MC, Bockenhauer
using https://sn.pub/cz9Cok. To use the app, D, Cadnapaphornchai MA, Dell KM, Kerecuk L,
please follow the instructions in Chap. 1. Liebau MC, Alonso-Peclet MH, Shneider B, Emre
S, Heller T, Kamath BM, Murray KF, Moise K,
Eichenwald EE, Evans J, Keller RL, Wilkins-Haug
L, Bergmann C, Gunay-Aygun M, Hooper SR, Hardy
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agement of X-linked hypophosphataemia. Nat Rev Gillion V, Gràcia-Garcia S, Halbritter J, Heidet L, van
Nephrol. 2019;15(7):435–55. den Heijkant M, Lemoine S, Knebelmann B, Emma
19. Blanchard A, et al. Gitelman syndrome: consensus F, Levtchenko E. Metabolic Nephropathy Workgroup
and guidance from a kidney disease: improving global of the European Reference Network for rare kid-
outcomes (KDIGO) controversies conference. Kidney ney diseases (ERKNet) and eUROGEN. Cystinuria:
Int. 2017;91(1):24–33. clinical practice recommendation. Kidney Int.
20. Langman CB, Deschênes G, Emma F, Goodyer P, 2020;99(1):48–58.
Lipkin G, Midgley JP, Ottolenghi C, Servais A, Soliman 24. Cochat P, Hulton S, Acquaviva C, Danpure CJ,
NA, Thoene JG, Levtchenko EN. Controversies and Daudon M, De Marchi M, Fargue S, Groothoff J,
research agenda in nephropathic cystinosis: conclu- Harambat J, Hoppe B, Jamieson NV, Kemper MJ,
sions from a “Kidney Disease: Improving Global Mandrile G, Marangella M, Picca S, Rumsby G,
Outcomes” (KDIGO) Controversies Conference. Salido E, Straub M, van Woerden CS, OxalEurope.
Kidney Int. 2016;89(6):1192–203. Primary hyperoxaluria Type 1: indications for screen-
21. Pearle MS, Assimos DG, Curhan G, Denu-Ciocca CJ, ing and guidance for diagnosis and treatment. Nephrol
Matlaga BR, Monga M, Penniston KL, Preminger Dialysis Transpl. 2012;27(5):1729–36.
GM, Turk TM, White JR. American Urological
Kidney Cancer
16
Rebecca Shone, Anna Walsh, Luke Stroman,
Christopher Anderson,
and Nicholas M. P. Annear
Clinical Scenario pole as well as a contralateral 26 mm right upper

A 48 year old male with no significant medical pole lesion (see CT images below in Fig. 16.1).
history is referred to urology with visible haema- No other sites of metastases were seen.
turia. A contrast CT reveals bilateral enhancing What is the most appropriate investigation
heterogenous masses; 65 mm in the left upper and management for this patient?
Fig. 16.1 Coronal contrast-enhanced CT scans showing a 65 mm left sided upper pole lesion (white arrow, left) and
23 mm right upper pole lesion (yellow arrow, right)
R. Shone · C. Anderson · N. M. P. Annear (*)

St George’s University Hospitals NHS Foundation
Trust, London, UK
e-mail: r.shone@nhs.net;
chris.anderson3@nhs.net; nannear@sgul.ac.uk
A. Walsh · L. Stroman
Trust, London, UK
e-mail: anna.walsh@stgeorges.nhs.uk;
luke.stroman@stgeorges.nhs.uk
https://doi.org/10.1007/978-3-031-09131-5_16
328 R. Shone et al.
Introduction noma (RCC) is the most common solid lesion in

the kidney and accounts for the majority of pri-
This chapter will discuss malignancies arising mary renal malignancies (approximately 90%)
from the renal parenchyma/cortex. These are a [1]. It will therefore be our primary focus for the
heterogenous group of cancers. Renal cell carci- purposes of this chapter (Tables 16.1 and 16.2).
Table 16.1 Principal Subtypes of RCC [1, 2]

Underlying genetic/histological characteristics Prognosis
Clear-cell (cc-RCC) Loss of chromosome 3p and mutation of the Worst prognosis of the three subtypes.
(75% of RCC) von Hippel-Lindau (VHL) gene frequently
found.
Papillary Type I—germline mutations of MET Low malignant potential, over 75% can
(15% of RCC) Type II—activation of the NRF2-ARE be treated by nephron sparing surgery [1].
pathway. Type I has best prognosis.
Chromophobe Typical genetic changes include loss of Good prognosis, high 5 and 10 year
(5% of RCC) chromosomes Y, 1, 2, 6, 10, 13, 17, 21. recurrence free survival [1].
Table 16.2 Other non-RCC renal tumour subtypes [1, 2]

Malignant
Tumour type Clinical potential Management
Renal medullary Rare tumour, median age of diagnosis Malignant Aggressive cancer with most patients
carcinoma 28 years [1]. presenting with metastatic disease.
Associated with sickle cell disease. Radical nephrectomy recommended,
even in early disease, along with
chemotherapy.
Not responsive to targeted anti-
angiogenic drugs including tyrosine
kinase inhibitors.
Carcinoma The lifetime risk of developing RCC is Malignant RCC associated with ESKD less
associated with 10 times higher for ESKD patients than aggressive than sporadic RCC.
ESKD; acquired the general population [1]. RCCs are Surgical management.
cystic disease - generally multifocal and bilateral.
associated RCC
Papillary adenoma Benign neoplasm arising from renal Benign Surveillance.
tubular epithelium. Measure ≤15 mm
in diameter. Histologically and
genetically indistinguishable from
papillary RCC. Estimated prevalence
of 20% based on autopsy series [3].
Hereditary kidney 5–8% of RCCs are hereditary. Variable May require repeated surgeries, nephron
tumours Examples of syndromes associated sparing approach favoured.
with development of renal tumours • HLRCC and SDH are aggressive
include: and require immediate surgical
• Von Hippel-Lindau (VHL) intervention
syndrome • Active surveillance for VHL, BHD
• Birt-Hogg-Dubé syndrome (BHD) and HPRCC—monitoring growth,
• Hereditary pRCC size and location.
• Tuberous sclerosis complex (TSC)
• Hereditary leiomyomatosis RCC
(HLRCC)
• Germline succinate dehydrogenase
(SDH) mutation
16 Kidney Cancer 329

Malignant
Tumour type Clinical potential Management
Angiomyolipoma Benign mesenchymal tumour—occurs Benign Active surveillance monitoring risk
(AML) sporadically or as part of tuberous factors for bleeding—Tumour size,
sclerosis complex (TSC). vascularity, and presence of tuberous
Slow growth rate, minimal morbidity. sclerosis complex [1].
Larger AMLs can cause localised pain Indications for active treatment include:
and spontaneous bleeding, which can • Persistent pain
be fatal. • Acute or repeated bleeding
• Large size (>4 cm)
In patients with tuberous sclerosis
complex (TSC), AML size and
vascularity may be reduced by mTOR
pathway inhibition.
Renal oncocytoma Benign tumour, representing 18% of Benign Challenging to diagnose with CT/MRI
solid renal tumours [1]. Slow growing. imaging as similar appearances to
RCC. Mainstay of treatment is
surveillance; radical/partial
nephrectomy is considered if increasing
size. Consideration of renal mass biopsy
may reduce unnecessary surgical
intervention.
Table 16.3 Risk factors associated with kidney cancer

Epidemiology and Causes
Risk Factor Comments
Smoking Risk increases proportional to amount
Kidney cancer is the ninth most commonly smoked. Kidney cancer risk is 33%
occurring cancer in men and the 14th most com- higher in current smokers compared
monly occurring cancer in women. The age- with non-smokers [5]
standardised rate per 100,000 in the US in 2018 Obesity There is an increased risk of kidney
cancer with increasing BMI. Multiple
was 10.9 per 100,000 [4]. proposed mechanisms include
The rate of new kidney cancers has been adipokine secretion from adipose
increasing since the 1990s, though seems to now tissue promoting tumour growth
be plateauing. This rise is thought to be at least Hypertension Well established risk factor,
proportional to the blood pressure [6]
partially attributable to the increasing numbers of
Workplace Certain occupation exposures such as
asymptomatic cancers detected incidentally exposures asbestos, cadmium, trichloroethylene
through CT scanning for other indications. Male sex Twice as common in men as women
It is estimated that half of kidney cancers Advanced Those with ESKD on dialysis have been
could potentially be prevented by weight loss and kidney disease shown to have a 2.3 times increased risk
of kidney cancer [7] this risk increases
tobacco smoking, which are the most potent risk further in those with ADPKD [8]
factors [5] (Table 16.3). Genetic/ Von Hippel-Lindau (VHL) syndrome,
hereditary Hereditary papillary renal cell
associations carcinoma (HPRCC), Hereditary
leiomyoma-renal cell carcinoma
(HLRCC), Birt-Hogg Dube (BHD)
syndrome, Familial renal cancer,
Cowden syndrome, Tuberous sclerosis
complex (TSC)
AL GRAWANY
330 R. Shone et al.
Genetic Basis of Kidney Cancer development of RCC. Other genetic mutations

frequently associated with RCC include PBRM1,
Kidney cancers are heterogenous and there are SETD2, BAP1 which, like VHL, are all located on
many associated genetic mutations. These have an the short arm of chromosome 3 (Fig. 16.2).
important clinical relevance in that they are the Other RCCs are characterised by mutations in
basis of the targeted and immunomodulatory ther- mammalian target of rapamycin (mTOR), a pro-
apies which are key to treating advanced kidney tein kinase involved in the regulation of cell
cancer. This will be explored later in the chapter. growth and proliferation which has been impli-
The VHL tumour suppressor gene is the most cated in the development of kidney cancer.
frequently mutated gene in sporadic RCC, and it In recent years, there has been much interest
is often the first mutation to occur. In normal in the immunological factors that allow tumour
cells, the VHL-containing complex targets the cells to proliferate. One such focus is the pro-
alpha subunit of hypoxia inducible factor (HIF-a) grammed cell death protein 1 (PD-1) receptor
for degradation. The mutation of VHL and subse- and its ligand (PD-L1). PD-1 is a cell surface
quent inactivation of VHL leads to accumulation receptor which regulates T cell activation, pro-
of HIF-a, leading to uncontrolled activation of moting apoptosis in antigen specific T cells.
HIF target genes, including vascular endothelial PD-1, PD-L1 and PD-L2 have been found to be
growth factor (VEGF), which control angiogen- abnormally expressed by tumour cells and lym-
esis and cellular proliferation. phocytes in the tumour microenvironment, where
The mutation in VHL is one of multiple poten- their inhibitory action assists the cancer cells’
tial genetic mutations which may occur in the evasion of the immune response.
Fig. 16.2 Pathophysiological mechanisms involved in FGFR (FGF receptor), PDGF (platelet-derived growth
the development of renal cell carcinoma (Adapted from factor), PDGFR (PDGF receptor) and VEGFR (VEGF
Choueiri TK, Motzer RJ. Systemic Therapy for Metastatic receptor), mechanistic target of rapamycin (mTOR),
Renal-Cell Carcinoma. N Engl J Med. 2017 Jan 26;376 MHC (major histocompatibility complex), PD-1 (pro-
(4):354–366 [9]) grammed cell death protein) PD-L1 (PD-1 ligand, and
Hypoxia-inducible factor (HIF), VEGF (vascular endo- PI3K (phosphatidylinositol 3-kinase)
thelial growth factor) FGF (fibroblast growth factor),
Clinical Presentation mass. Less than 10% of patients present with

these symptoms however, and those who do are
More than 50% of RCCs are diagnosed inciden- likely to have locally advanced disease [1]
tally. The classic presenting triad includes hae- (Fig. 16.3 and Table 16.4).
maturia, flank pain and a palpable abdominal
Fig. 16.3 Clinical Systemic Symptoms:

Presentation of RCC [1] • Fever
Signs of a • Weight loss
hereditary
underlying • Sweats
syndrome • Pallor
• Cachexia
• Myoneuropathy
Hepatic dysfunction Palpable abdominal

Flank Pain mass
Haematuria
Scrotal varicocele
(majority are left-
sided)
Lower limb oedema
Table 16.4 Paraneoplastic Syndromes associated with RCC [1]

Paraneoplastic
phenomena Cause(s) Clinical manifestation
Fever Cytokine production by the tumour cells, Fever, night sweats
particularly IL-1, IL-6 and TNF-β
Anaemia Inflammation/chronic disease Fatigue, breathlessness
Erythrocytosis Excess erythropoietin (EPO) Occurs in 1–5% of patients with
advanced RCC
Hypercalcaemia Over production of PTH-r protein. Clinical signs of hypercalcaemia—
Lytic bone lesions. Constipation, confusion
Bone pain
Hypercortisolism Excess ACTH Cushing’s syndrome
Hepatic dysfunction Liver metastases. Jaundice, itch, right upper quadrant
Stauffer syndrome refers to hepatic dysfunction pain
in the absence of liver metastases May be asymptomatic
Secondary (AA) Deposition of fibril proteins. Clinical presentation depends on organ
amyloidosis affected
332 R. Shone et al.
Given the paraneoplastic presentations of The most important criterion for differentiating
RCC, patients can present with a myriad of malignant lesions is the presence of enhance-
symptoms related to this, including: ment, with contrast enhanced CT and MRI being
the modalities of choice. For the diagnosis of
• Systemic symptoms of fever, weight loss, complex renal cysts, MRI may be preferable: it
sweats, pallor, cachexia, myoneuropathy has higher sensitivity and specificity for small
• Signs of hepatic dysfunction cystic renal masses and tumour thrombi. Contrast
• Lower limb oedema—may represent inferior enhanced ultrasound also has a high sensitivity
vena cava involvement and specificity.
• Scrotal varicocele The Bosniak Classification is used to stratify
• Signs of an underlying hereditary syndrome cysts by their radiological features on cross-
sectional imaging and thus determine a suitable
work up and follow up plan (Table 16.5).
Investigations
Practice point 1
Imaging is key to diagnosis: Most renal
masses can be diagnosed accurately by
imaging alone
Table 16.5 Bosniak Bosniak Features Clinical implications

Classification of Renal Category
Cysts [1] I • Simple cyst Benign, no follow up needed
• Hairline-thin wall without septa,
calcification or solid components
• Non-enhancing
II • Minimally complex Benign, no follow up needed

• May contain a few hairline-thin septa
• Fine calcification in wall or septa
• Non-enhancing, high attenuation
• <3 cm in size
IIF • Minimally complex Some are malignant, require US /

• May contain more hairline-thin septa CT / MRI follow up over 5 years at 6
with non-measurable enhancement monthly intervals
• May contain calcification, nodular or
thick
III • Indeterminate cystic mass Over 50% are malignant1

• Thickened, irregular walls or septa with
enhancement Need active surveillance or surgery
IV • Clearly malignant 100% malignant

• Solid mass with large cystic or a
necrotic component Surgical intervention required.
Renal Tumour Biopsy
The vast majority of kidney cancer diagnoses are

made on the basis of the radiological findings. In
certain situations however, tumour biopsy is indi-
cated (Table 16.6).
Biopsy should be avoided in comorbid and
frail patients who, regardless of histology, would
not be considered for active management [1].
Percutaneous sampling can be performed with
local anaesthesia under US or CT guidance with
needle core biopsy. Given concerns regarding
tumour seeding along the needle tract, a co-axial
technique is recommended. When performed by
experienced operators, core biopsy carries a high
diagnostic yield, with a metanalysis reporting sen-
sitivity of 99.1% and specificity of 99.7% for the
diagnosis of malignancy [10]. In cases where there Fig. 16.4 Co-axial technique for biopsy of a kidney
mass
is a suspicion of malignancy but the biopsy result is
non-diagnostic, a repeat biopsy or surgical explora-
tion should be considered [1] (Fig. 16.4).
Diagnosis and Classification
The approach to classifying renal cell carcinoma

A larger gauge needle or cannula is advanced involves consideration of both the stage (how
into the mass; once adequately positioned a locally advanced the tumour is) and grade (the
smaller needle is placed through it in order resemblance of the tumour cells to healthy cells).
to obtain tissue. This allows for multiple The TNM classification is universally recognised
needle biopsies via only 1 point of access, as the staging tool of choice (Tables 16.7, 16.8,
thereby reducing risk of tumour seeding. 16.9 and Fig. 16.5).
Table 16.6 Indications for renal tumour biopsy [1]

Indications for renal tumour biopsy [1]
• Further assessment of radiologically indeterminate
masses or in the presence of another primary
malignancy
• Prior to ablative treatments (cryotherapy/
radiofrequency ablation)
• Where active surveillance is being considered
• To select most suitable treatment strategy in
metastatic disease
334 R. Shone et al.
Table 16.7 TNM T – Primary Tumour N – Regional M – Distant

Classification [1] Lymph Nodes metastases
T1 – N0 – M0 –
Tumour ≤ 7 cmin greatest dimension, limited to kidney No regional No distant
o T1a – Tumour ≤ 4 cm lymph node metastasis
o T1b – Tumour >4 cm but ≤ 7cm metastases
T2 – N1 – M1 –
Tumour >7 cm in greatest dimension but limited to kidney Metastasis in Distant
o T2a - Tumour >7 cm but ≤ 10cm regional lymph metastasis
o T2b – Tumour >10 cm but limited to the kidney nodes.
T3 – NX –
Tumour extends into major veins or perinephric tissues but Regional lymph
not into ipsilateral adrenal gland and not beyond Gerota’s nodes cannot
fascia be assessed
o T3a - Tumour extends into renal vein or invades
perirenal fat but not beyond Gerota fascia
o T3b – Tumour extends into vena cava below
diaphragm
o T3c – Tumour extends into vena cava above the
diaphragm
T4 – Tumour invades beyond Gerota’s fascia
Table 16.8 TNM Stage Grouping [1]
The TNM staging is summarised as RCC Stage 1-4:

Stage 1 T1 N0 M0
Stage 2 T2 N0 M0
Stage 3 T3 N0 M0
T1, T2, T3 N1 M0
Stage 4 T4 Any N M0
Any T Any N M1
Table 16.9 World Health Grade 1 Nucleoli absent or inconspicuous and basophilic at
Organisation (WHO)/ 400 x magnification
International Society of
Urologic Pathology (ISUP) Grade 2 Nucleoli clearly visible and eosinophilic at 400 x
Tumour Grading [1] magnification
Grade 3 Nucleoli conspicuous and eosinophilic at 100 x
magnification
Grade 4 Extreme nuclear pleomorphism, multinucleate cells,
rhabdoid or sarcomatoid differentiation.
– ≤
– ≤
– ≤
–
–
’
–
–
’
’
Fig. 16.5 Staging of kidney cancer [1]
Management Surgery can include both partial nephrectomy

(PN), also known as “nephron sparing” surgery
Surgery (NSS) or radical nephrectomy (RN), which
involves excision of the entire kidney and
When patients present with localised disease, the Gerota’s fascia. Excision of the ureter along with
mainstay of treatment is surgery, which can be the kidney is a nephroureterectomy and per-
curative. It is therefore the preferred first line formed for urothelial cell malignancy of the
treatment for the majority of patients with stage I, upper tract. Imperative indications for PN include
II or III disease. a solitary kidney, bilateral renal tumours or
patients with syndromes pre-disposing to renal
malignancy.
Practice Point 2 Patients with advanced or metastatic disease
Surgery is the first line treatment for local- with a favourable prognosis who have a resect-
ised disease able primary tumour may also benefit from surgi-
cal resection where this is technically feasible
336 R. Shone et al.
Table 16.10 Comparison Partial nephrectomy (PN) Radical nephrectomy (RN)

between partial and radical “Nephron sparing”
nephrectomy [1] Preferred option for all T1a and some T1b/T2 Option for larger tumours or more locally
tumours. invasive disease where PN not possible
• A Cochrane review found that for localised • Minimally invasive vs open approach – no
disease, PN was associated with reduced RCT has addressed oncological outcomes
time to death of all-cause mortality. Serious with either approach though minimally
adverse events, CSS and time to recurrence invasive associated with lower morbidity
were similar between groups10 • Less likely to have positive surgical
• Several retrospective analyses have margins with RN vs PN11
suggested a decreased cardiovascular
specific mortality with PN versus RN1
• PN should be surgery of choice, even if it
necessitates an open procedure where RN
could be minimally invasive
• Absolute indications for PN include:
o a solitary kidney
o bilateral renal tumours
o patients with syndromes pre-disposing to
renal malignancy
• PN is preferred option for patients with pre-
existing CKD to limit progression of ESKD
requiring kidney replacement therapy (KRT)
(Table 16.10). For most patients with metastatic Alternatives to Surgery

disease further systemic treatment is then war-
ranted which will be discussed in more detail Alternatives to surgery include:
below. When surgical resection is performed in
the presence of metastatic disease this is termed a • Watchful waiting
cytoreductive nephrectomy (CN). • Active Surveillance
• Cryoablation
Adrenalectomy • Radiofrequency Ablation
Ipsilateral adrenalectomy during PN or RN has
not been found to have a survival advantage atchful Waiting & Active Surveillance
W
unless there is clinical evidence of gland invasion The increasing incidental detection of small renal
(T4 disease) [1]. masses (SRMs), especially in a predominantly
elderly population, has led to the development of
ymph Node Dissection (LND)
L active surveillance protocols. In carefully
The only randomised trial to date has not shown selected patients, this may be an appropriate ini-
a survival advantage of LND in localised disease tial strategy to monitor their renal mass, which
[13]. Retrospective studies have shown a survival could then be treated at a later date if it is seen to
benefit with visible LN disease [14]. progress. Studies suggest that up to 20% of small
renal masses are benign, with only 20% having
an aggressive phenotype [16].
Practice Point 3 Active surveillance differs from watchful
Despite attempted curative treatment with waiting, which is reserved for those patients who
nephrectomy (either partial or radical), would not be candidates for active treatment, and
approximately 30% of patients with ccRCC who therefore do not usually require follow up
with localised disease will go onto develop imaging (Fig. 16.6).
metastases [15] Other less-invasive treatments are also avail-
able for those who may not be fit for surgery,
History and History and

examination 6 monthly Annually for
examination
5 years
Bloods for 2 years Bloods
Imaging (CT or Imaging (CT or MRI)
MRI)
Fig. 16.6 Follow up of patients under active surveillance [1]
PN
Surgical candidate or
minimally invasive RN
Localised disease
Active surveillance
Elderly / comorbid with or
small lesion
RFA / Cryoablation
Clear cell histology Clinical trial enrolment

RN
+ adrenalectomy if evidence of gland invasion
Advanced or
+ LND if evidence of nodal disease
Node positive disease
+ Remove tumour thrombus if venous
involvement
Non clear cell histology Active surveillance
Resectable CN +/- metastatectomy
Metastatic disease Systemic therapy
Non resectable Tissue sampling
Fig. 16.7 Management of Kidney Cancer [1]

PN Partial nephrectomy, RN Radical nephrectomy, RFA
Radiofrequency ablation, CN Cytoreductive nephrectomy,
LND Lymph node dissection
have small (<4 cm tumours) or those who have argon coolant is delivered at subfreezing temper-
multiple and/ or bilateral tumours. These treat- atures. This forms an ‘ice ball’ around the probe
ments include cryotherapy and radiofrequency tip, destroying the tumour tissue. Helium is then
ablation. There are currently no data demonstrat- passed through the probe to induce a slow thaw.
ing any oncological benefit of these treatments In most cases, two freeze-thaw cycles are
over PN, although benefit has been shown in performed.
reduction in loss of kidney function. Increased
local recurrence has been seen when compared to adiofrequency Ablation (RFA)
R
partial nephrectomy but cancer specific survival Percutaneous RFA can be carried out under local
is similar [17]. anaesthesia and sedation or general anaesthetic.
One or more radiofrequency electrodes are
Cryoablation inserted percutaneously into the tumour under
Cryoablation can be performed by either the per- imaging guidance. Radiofrequency energy is
cutaneous or laparoscopic route, with no signifi- then delivered via the electrode to create high
cant difference in complication between the two temperatures and destroy the tumour tissue.
routes. Under ultrasound or CT guidance, a probe Figure 16.7 summarises the approach to man-
is inserted into the tumour through which an agement of kidney cancer.
338 R. Shone et al.
Systemic Therapy pies, IL2/IFN-α. The mechanism of action of sys-

temic therapies are shown in Table 16.12 and
Fig. 16.9.
Practice Point 4
Small molecule inhibitors, targeted thera-
pies and immune checkpoint-based immu- Table 16.11 International Metastatic RCC Database
Consortium (IMDC) criteria for predicting survival in
notherapy form the treatment pathway for patients with metastatic RCC [1]
advanced or metastatic kidney cancer.
IMDC criteria: Factors predicting poorer outcome
There is no role for chemotherapy [1] include
• Less than one year from time of diagnosis to
systemic therapy
Treatment options are selected based on risk • Performance status <80% (Karnofsky performance
status (KPS) scale)
scoring and histology. The most commonly used • Haemoglobin less than lower limit of normal
risk scoring models are the Memorial Sloan • Calcium greater than upper limit of normal
Kettering Cancer Center (MSKCC) Prognostic • Neutrophils greater than upper limit of normal
Model or the International Metastatic Renal Cell • Platelets greater than upper limit of normal
Carcinoma Database Consortium (IMDC) Favourable risk: No prognostic factors
Intermediate risk: 1–2 prognostic factors
Criteria. Here, we will focus on the IMDC crite- Poor risk: 3 or more prognostic factors
ria which is most commonly used (Table 16.11 Table adapted from https://www.mdcalc.com/
and Fig. 16.8). The MSKCC calculator is based imdc-international-metastatic-rcc-database-consortium-
on the older and no longer utilised immunothera- risk-score-rcc
Alternative in patients who

cannot receive or tolerate
Standard of Care
immune checkpoint
inhibitors
IMDC Favorable Risk Sunitinib

Pembrolizumab + Axitinib
Or
Pazopanib
Cabozantinib
IMDC Intermediate and Pembrolizumab + Axitinib Or
Poor Risk Or Sunitinib
Ipilimumab + Nivolumab Or
Pazopanib
Fig. 16.8 Selection of therapy in metastatic kidney cancer (Adapted from EAU Guidelines [1])
Table 16.12 Systemic Mechanism of Action Agents

therapies used in the Tyrosine kinase inhibitors Sorafenib, sunitinib, pazopanib, axitinib,
treatment of advanced
Targeted Therapies
Lenvatinib, cavozantinib
kidney cancer
Monoclonal antibody against Bevacizumab

circulating VEGF
mTOR inhibitors Temsirolimus, everolimus
PD-1 inhibitors Pembrolizumab, nivolumab

Immunotherapy
PDL-1 inhibitors Avelumab
CTLA-4 inhibitors Ipilimumab
Fig. 16.9 Mechanism of action of targeted and immuno- FGFR (FGF receptor), PDGF (platelet-derived growth
logical therapies factor), PDGFR (PDGF receptor) and VEGFR (VEGF
(Adapted from Choueiri TK, Motzer RJ. Systemic Therapy receptor), mechanistic target of rapamycin (mTOR),
for Metastatic Renal-Cell Carcinoma. N Engl J Med. MHC (major histocompatibility complex), PD-1 (pro-
2017 Jan 26;376 (4):354–366 [9]) grammed cell death protein) PD-L1 (PD-1 ligand, and
Hypoxia-inducible factor (HIF), VEGF (vascular endo- PI3K (phosphatidylinositol 3-kinase)
thelial growth factor) FGF (fibroblast growth factor),
AL GRAWANY
340 R. Shone et al.
Prognosis Follow up
The prognosis depends on stage of the kidney Surveillance following treatment aims to detect
cancer as shown in Fig. 16.10 local recurrence or metastatic disease while the
patient is still curable. Controversy exists regard-
ing the optimal duration/intervals for follow up
of patients who have completed treatment for
RCC, and there is no existing evidence base to
Distant disease (Stage IV) guide clinicians. The surveillance modality is
12%
guided by the individual patient’s risk profile.
Factors increasing risk include larger tumours
(>7 cm), or when there is a positive surgical mar-
Reginal disease (Stage III)
70% gin. Follow up following cryoablation or RFA
may be more intensive due to the higher recur-
rence rate (Table 16.13).
Localised disease (Stage I+II)
93%
Practice Points
1. Imaging is key to diagnosis: most
renal masses can be diagnosed accu-
Fig. 16.10 Renal Cell Cancer 5 year percentage survival rately by imaging alone
by stage [18] 2. Surgery is the first line treatment for
localised disease
3. Despite attempted curative treatment
with nephrectomy (either partial or rad-
ical), approximately 30% of patients
with ccRCC with localised disease will
go onto develop metastases [15]
4. Small molecule inhibitors, targeted
therapies and immune checkpoint-
based immunotherapy form the treat-
ment pathway for advanced or
metastatic kidney cancer; There is no
role for chemotherapy [1]
Table 16.13 Proposed Surveillance Schedule (Adapted from EAU Guidelines [1])
Surveillance interval
Risk Profile
3 mo 6 mo 12 mo 18 mo 24 mo 30 mo 36 mo >3 year
CT every
Low CT - CT - CT
- - 2 years
CT
Intermediate - CT CT CT CT
- yearly
CT
High CT CT CT CT CT - CT
yearly
(CT should be contrasted if possible, or appropriate imaging schedule agreed with radiologists)
Conclusions to be radiologically indeterminate: a needle

core biopsy was performed on the left, which
The treatment of kidney cancer has evolved rap- revealed an ISUP Grade 2 Papillary RCC. A
idly over the preceding two decades with the left-sided laparoscopic radical nephrectomy
advent of targeted and immunotherapies. In was performed. Histology confirmed papillary
future, these treatment modalities are likely to RCC, stage T1a. Follow-up using a CT scan
become more individualised with the use of was planned 6 months post-operatively for sur-
genetic sequencing and biomarkers. veillance of the contralateral mass. A fast rate
As we reflect on the 48-year-old gentleman of growth would prompt a biopsy and subse-
with haematuria and two solid kidney lesions quent partial nephrectomy if this contralateral
identified on CT imaging, whom we met at the lesion was also found to be malignant.
start of this chapter, his case was discussed in a
urological multidisciplinary meeting. On
review of his imaging, the lesions were thought Appendix 1
Table 16.14 Karnofsky Performance Status Score (adapted from mdcalc.com/karnofsky-performance-status-

scale) [19]
Description Points Assigned Description
Normal no complaints; no evidence of disease 100
Able to carry on normal activity; minor signs or Able to carry on normal
90
symptoms of disease activity and to work; no
Normal activity with effort; some signs or symptoms special care needed
80
of disease
Cares for self; unable to carry on normal activity or to
70 Unable to work; able to
do active work
live at home and care
Requires occasional assistance, but is able to care for
60 for most personal
most personal needs
needs; varying amount
Required considerable assistance and frequent
50 of assistance needed.
medical care
Disabled; required special care and assistance 40
Unable to care for self;
Severely disabled; hospital admission is indicated
30 requires equivalent of
although death not imminent
institutional or hospital
Very sick; hospital admission necessary; active
20 care; disease may be
supportive treatment necessary
progressing rapidly.
Moribund; fatal processes progressing rapidly 10
Dead 0 n/a
Adapted from: Karnofsky DA Burchenal JH. (1949). ‘The Clinical Evaluation of Chemotherapeutic Agents in Cancer.’
In: MacLeod CM (Ed), Evaluation of Chemotherapeutic Agents. Columbia Univ Press. Page 196
342 R. Shone et al.
Questions A. Incorrect—the classical triad of haema-

turia, flank pain and a palpable abdomi-
nal mass is seen in <10% of patients.
1. Which of the following is not a recognised B. Incorrect—Most patients are asymp-
risk factor for the development of kidney tomatic and diagnosed incidentally.
cancer? C. Correct—Most kidney cancers are diag-
A. Smoking nosed incidentally through imaging for
B. Obesity other reasons.
C. Asbestos exposure D. Incorrect—Scrotal varicoceles are a rare
D. Alcohol sign of kidney cancer.
E. Male sex E. Incorrect—Absence of haematuria
Answer: D alone does not necessarily confer a more
A. Incorrect—Smoking is a well- favourable prognosis. However, where
established risk factor for kidney cancer. patients do present with the classical
B. Incorrect—The risk of developing kid- triad of haematuria, flank pain and a pal-
ney cancer increases with BMI. pable abdominal mass, they are more
C. Incorrect—Asbestos, along with other likely to have locally advanced disease.
occupational exposures such as trichloro- 3. An 84 year old lady presents to the emer-
ethylene, increase the risk of kidney gency department with abdominal pain and
cancer confusion. She has a known 3 cm lesion on
D. Correct—In fact, alcohol has been found the lower pole of the left kidney (Bosniak
to have a protective effect, whereby those IIF) which is under active surveillance by her
who drink up 2 alcoholic drinks per day urologist. On admission her blood tests dem-
have a reduced risk of kidney cancer onstrate the following: adjusted calcium
compared with non-drinkers. Alcohol 3.1 mmol/L, PTH 15 pmol/L, vitamin D
intake is however associated with an 30 nmol/L, creatinine 80 μmol/L (eGFR
increased risk of other diseases and can- 64 ml/min/1.73 m [2]). Her other blood tests
cers in other solid organs. are unremarkable. What is the most likely
E. Incorrect—Kidney cancer is twice as cause of her hypercalcaemia?
common in men compared to women. A. Production of PTH related peptide
2. As far as the presenting features of kidney B. Primary hyperparathyroidism
cancer are concerned, which of the following C. Metastatic bone disease
statements is true? D. Vitamin D deficiency
A. Haematuria, flank pain and a palpable E. Secondary hyperparathyroidism.
abdominal mass is the recognised pre- Answer: B
senting triad for the majority of patients. A. Incorrect—production of PTH related
B. More than half of patients present with a peptide would lead to hypercalcaemia
manifestation of a paraneoplastic syn- which in turn would cause the PTH to be
drome rather than symptoms of the RCC suppressed, rather than elevated which it
itself. is in this case. There is a specific labora-
C. The majority of kidney cancers are diag- tory test for PTHrP. Levels of PTHrP do
nosed incidentally not cause elevation in native PTH
D. Varicoceles are a common presenting detection.
symptom in men. B. Correct—This patient has primary
E. Absence of haematuria confers a more hyperparathyroidism as evidenced by
favourable prognosisAnswer: C hypercalcaemia in the setting of a raised
PTH. Given the degree of hypercalcae- E. Incorrect—Surgery would be the man-

mia the PTH should be low. agement of choice given the size of his
C. Incorrect—If the hypercalcaemia was a tumour and the lack of contraindications
result of bone metastases, PTH would be to surgery.
suppressed rather than elevated. 5. A 94 year old lady with a background of
D. Incorrect—Though the vitamin D is CKD stage G4, ischaemic heart disease, pre-
low, this is not responsible for the hyper- vious stroke, heart failure with reduced ejec-
calcaemia. Low vitamin D is more likely tion fraction and newly diagnosed
to cause hypocalcaemia. Alzheimer’s dementia is incidentally found
E. Incorrect—Secondary hyperparathy- to have an indeterminate 4 cm cystic mass in
roidism occurs in response to hypocal- the right kidney (Bosniak III) Which of the
caemia where the parathyroid glands following management options is most
hypertrophy and produce excess PTH, appropriate?
commonly seen in chronic kidney dis- A. Renal tumour biopsy
ease stage 3 and above. B. Active surveillance
4. An active 64 year old man with a background C. Radiofrequency ablation
of hypertension undergoes a CT scan of the D. Partial nephrectomy
abdomen in his local emergency department E. Watchful waitingAnswer: E
after presenting with abdominal pain. He is A. Incorrect—though the cystic mass is
found to have an 8 cm solid lesion in the indeterminate, which is an indication for
upper pole of the right kidney which is staged biopsy, the guidelines are clear that renal
as T2a N0 M0. Which of the following treat- tumour biopsy should only be undertaken
ments would be most likely to be where it is likely to change management.
recommended? Given this patient’s age and co-
A. Active surveillance morbidities she is unlikely to be a candi-
B. Radical nephrectomy with ipsilateral date for surgical treatment, regardless of
adrenalectomy the biopsy findings.
C. Partial nephrectomy B. Incorrect—Active surveillance would
D. Radical nephrectomy involve 6 monthly assessment and
E. Radiofrequency ablation imaging for 2 years and annual follow
Answer: C up thereafter. Even if the kidney lesion
A. Incorrect—Given this man’s age and was found to have grown in size, this
lack of significant co-morbidities, a lady would not be candidate for
definitive management strategy by way treatment.
of partial nephrectomy would be C. Incorrect—Given her co-morbidities
recommended. and age she is not fit for RFA.
B. Incorrect—Firstly, partial nephrectomy D. Incorrect—Given her co-morbidities
is preferred over radical nephrectomy, and age she is not fit for surgery.
secondly, adrenalectomy in only indi- E. Correct—Watchful waiting differs from
cated where there is evidence of gland active surveillance in that no routine re-
invasion. imaging or regular assessment is require-
C. Correct—Surgery is the management of ment. Given this patient’s extensive
choice for localised kidney cancer and co-morbidities this would be the most
partial nephrectomy is preferred where appropriate option.
possible 6. A 64 year old male is found to have an iso-
D. Incorrect—Partial nephrectomy is the lated enhancing 3 cm solid kidney mass on
preferred option for localised tumours CT imaging with no evidence of lymph node
where surgically feasible . involvement or metastatic spread. You are
344 R. Shone et al.
referring to the urology registrar on the tele- C. Incorrect—a contrast-enhanced CT or

phone, who wants to know what stage his MRI is advocated, with a preference for
cancer appears to be. MRI in cystic lesions, where MRI has a
A. T1a; N0; M0 higher sensitivity and specificity for
B. T2b; N1; M0 small cystic renal masses and tumour
C. T3; N0; M1 thrombi. The most important criterion for
D. T4; N1; M1 differentiating malignant lesions is the
E. T1b; N0; M0 presence of enhancement so the use of
Answer: A contrast is essential.
A. Correct—the isolated enhancing solid D. Incorrect—a contrast-enhanced CT or
kidney mass is <4 cm diameter and is MRI is advocated, with a preference for
limited to the kidney MRI in cystic lesions, where MRI has a
B. Incorrect—the isolated enhancing solid higher sensitivity and specificity for small
kidney mass is <4 cm diameter and is cystic renal masses and tumour thrombi.
limited to the kidney Most lesions can be diagnosed on the
C. Incorrect—the isolated enhancing solid basis of imaging alone, avoiding the need
kidney mass is <4 cm diameter and is for an unnecessary invasive procedure.
limited to the kidney E. Incorrect—a contrast-enhanced CT or
D. Incorrect—the isolated enhancing solid MRI is advocated, with a preference for
kidney mass is <4 cm diameter and is MRI in cystic lesions, where MRI has a
limited to the kidney higher sensitivity and specificity for
E. Incorrect—the isolated enhancing solid small cystic renal masses and tumour
kidney mass is <4 cm diameter and is thrombi. MAG-3 will give functional
limited to the kidney information about both kidneys only.
7. A 48 year old female of normal intellect and 8. A fit, independent 72 year old gentleman has
no other comorbidity is found to have a cys- a successful laparoscopic partial left nephrec-
tic lesion on her right kidney—of around tomy for stage T1a N0 M0 renal cell cancer,
3 cm in diameter. What is the most appropri- with clear tumour margins on resection. His
ate next investigation? serum creatinine at one month post-procedure
A. Contrast enhanced CT is 94 μmol/L (1.06 mg/dL). How should he
B. Contrast enhanced MRI be followed up?
C. Non-contrast CT A. Discharge from follow-up
D. Biopsy of the renal lesion B. Non-contrast CT at 1 year
E. MAG-3 scan C. Non-contrast MRI at 3 months
Answer: B D. Ultrasound at 6 months
A. Incorrect—a contrast-enhanced CT or E. Contrasted CT at 6 months
MRI is advocated, with a preference for Answer: E
MRI in cystic lesions, where MRI has a A. Incorrect—Whilst this gentleman’s
higher sensitivity and specificity for 5 year survival with localised stage I dis-
small cystic renal masses and tumour ease is around 93%, there is still a signifi-
thrombi. cant risk of developing recurrence or
B. Correct—a contrast-enhanced CT or metastases of up to 30%
MRI is advocated, with a preference for B. Incorrect—Non-contrast CT is not
MRI in cystic lesions, where MRI has a appropriate to follow up this patient with
higher sensitivity and specificity for normal renal function.
small cystic renal masses and tumour C. Incorrect—Non-contrast MRI is not
thrombi. optimal to follow up this patient with
normal renal function. Furthermore, C. Incorrect—Watchful waiting is reserved

imaging within 3 months is only indi- for patients who are not candidates for
cated for patients with a high recurrence active treatment and who therefore do
risk. The history does not suggest that he not require follow up imaging. In this
falls into this category so repeat imaging case, active surveillance with regular
within 6 months would be sufficient. imaging is more appropriate as this
D. Incorrect—Ultrasound is of insufficient patient would be a surgical candidate if
sensitivity to detect metastatic spread. her lesion was found to have grown rap-
E. Correct—Contrasted CT of the chest idly in size or metastasised.
and abdomen is the recommended follow D. Correct—This lady’s recent myocar-
up modality for low-risk localised dis- dial event makes immediate surgery
ease post partial nephrectomy with cura- risky. Given her localised disease and
tive intent comorbidity, active surveillance is the
9. A 58 year old female with CKD stage G4 most appropriate option to allow her
secondary to diabetes mellitus, with concom- medical condition to stabilise, with
itant ischaemic heart disease is found to have consideration of definitive surgical
an incidental 2 cm solid kidney lesion on therapy in the form of partial nephrec-
ultrasound, which is confirmed on CT imag- tomy or ablative therapy—if appropri-
ing, with no nodal involvement or metasta- ate—at a later stage.
ses. She had a non-ST elevation myocardial E. Incorrect—This lady’s recent myocar-
infarction 3 months ago. What is the most dial event makes immediate surgery
appropriate management for her? risky. Given her localised disease and
A. Immediate partial nephrectomy comorbidity, active surveillance would
B. Urgent radical nephrectomy be more appropriate to allow her medical
C. Watchful waiting condition to stabilise, with consideration
D. Active Surveillance of definitive surgical therapy in the form
E. Start Pembrolizumab and Axitinib of partial nephrectomy or ablative ther-
Answer: D apy—if appropriate—at a later stage.
A. Incorrect—This lady’s recent myocar- There is no evidence of metastatic spread
dial event makes immediate surgery to warrant systemic therapy.
risky. Given her localised disease and 10. A 45 year old female primary school teacher
comorbidity, active surveillance would has been found to have T2aN1M1 renal cell
be more appropriate to allow her medical cancer on a delayed follow-up scan, having
condition to stabilise, with consideration elected for active surveillance 18 months
of definitive surgical therapy in the form ago. She has CKD stage G3a (serum creati-
of partial nephrectomy or ablative ther- nine 148 μmol/L (1.67 mg/dL)—eGFR
apy—if appropriate—at a later stage. 50 ml/min/1.73 m [2]). All full blood count
B. Incorrect—This lady’s recent myocar- parameters remain in the normal range, as
dial event makes immediate surgery does her serum calcium level. She otherwise
risky. Given her localised disease and remains well, having prospectively arranged
comorbidity, active surveillance would cover for her class to attend the renal clinic
be more appropriate to allow her medical with you to follow up her scan results. You
condition to stabilise, with consideration rightly refer for her case for consideration
of definitive surgical therapy in the form urgently in the Uro-Oncology MDT meeting.
of partial nephrectomy or ablative ther- What is the most likely management for her
apy—if appropriate—at a later stage. current disease?
346 R. Shone et al.
A. Urgent partial nephrectomy Test your learning and check your understand-
B. Urgent radical nephrectomy and ing of this book’s contents: use the “Springer
metastasectomy Nature Flashcards” app to access questions using
C. Watchful waiting https://sn.pub/cz9Cok. To use the app, please fol-
D. Active Surveillance low the instructions in Chap. 1.
E. Consideration for cytoreductive nephrec-
tomy, metastasectomy and consideration
of first line systemic therapy with References
Pembrolizumab and Axitinib
1. European Association of Urology. Guidelines on
Answer: E
Renal Cell Carcinoma. [Online] EAU Guidelines
A. Incorrect—This lady has new metastatic Office, Arnhem, The Netherlands; 2021. https://
renal cell cancer, which warrants cytore- uroweb.org/guideline/renal-c ell-c arcinoma/.
ductive nephrectomy, metastasectomy Accessed 5 July 2021.
2. Cancer Research UK. Kidney cancer: types and
and consideration of first line systemic
grades; 2020. https://www.cancerresearchuk.org/
therapy with Pembrolizumab and about-c ancer/kidney-c ancer/stages-t ypes-g rades/
Axitinib, since partial nephrectomy alone types-grades. Accessed 30 Nov 2020.
will not be sufficient to fully treat her 3. Caliò A, Warfel KA, Eble JN. Papillary adenomas and
other small epithelial tumors in the kidney: an autopsy
disease
study. Am J Surg Pathol. 2019;43(2):277–87.
B. Incorrect—This lady has new metastatic 4. World Cancer Research Fund. Kidney cancer statis-
renal cell cancer, which warrants cytore- tics; n.d. https://www.wcrf.org/dietandcancer/kidney-
ductive nephrectomy, metastasectomy cancer-statistics/. Accessed 30 Nov 2020].
5. Cumberbatch MG, Rota M, Catto JW, et al. The
role of tobacco smoke in bladder and kidney carci-
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Axitinib, since radical nephrectomy and analysis of incidence and mortality risks. Eur Urol.
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6. Hidayat K, Du X, Zou S, et al. Blood pres-
fully treat her disease
sure and kidney cancer risk. J Hypertens.
C. Incorrect—This lady has new metastatic 2017;35(7):1333–44.
renal cell cancer, which warrants cytore- 7. Wong G, Staplin N, Emberson J, et al. Chronic kidney
ductive nephrectomy, metastasectomy disease and the risk of cancer: an individual patient
data meta-analysis of 32,057 participants from six
prospective studies. BMC Cancer 2016; 16(1).
therapy with Pembrolizumab and 8. Hajj P, Ferlicot S, Massoud W, Awad A, Hammoudi
Axitinib – watchful waiting would inevi- Y, Charpentier B, Durrbach A, Droupy S, Benoît
tably lead to further disease spread, and G. Prevalence of renal cell carcinoma in patients
with autosomal dominant polycystic kidney
would not be the most appropriate line of
disease and chronic renal failure. Urology.
management for a young, fit patient. 2009;74(3):631–4.
D. Incorrect—This lady has new metastatic 9. Choueiri TK, Motzer RJ. Systemic therapy for
renal cell cancer, following delayed re- metastatic renal-cell carcinoma. N Engl J Med.
2017;376(4):354–66.
imaging on active surveillance. Her cur-
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cytoreductive nephrectomy, metastasec- SE, Hora M, Kuczyk MA, Merseburger AS, Mulders
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A. Systematic review and meta-analysis of diagnostic
Pembrolizumab and Axitinib
accuracy of percutaneous renal tumour biopsy. Eur
E. Correct—This lady has new metastatic Urol. 2016;69(4):660–73.
renal cell cancer, which warrants consid- 11. Kunath F, Schmidt S, Krabbe LM, Miernik A, Dahm
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Hemodialysis in Clinical Practice
17
Mohamed Elewa and Sandip Mitra

A 64 year old lady with end stage kidney disease
secondary to polycystic kidney disease, is now ‘Dialysis’ is defined as “The separation of par-
anuric, and has been on treatment with high flux ticles in a liquid on the basis of differences in
hemodialysis for 6 years using a dialysis cathe- their ability to pass through a membrane”.
ter. She is on conventional HD 3.5 h three times Clinically, the movement of substances between
week, achieving a blood flow of 275 mL/min. the blood and dialysis fluid compartment across
Hemodialysis treatment has been complicated by an artificial semipermeable membrane for
predialysis hyperkalemia, frequent alarms of blood purification is hemodialysis. Thomas
high venous pressures, streaky washbacks, Graham, often dubbed the “Father of Dialysis”,
high interdialytic weight gains and dialysis described the diffusion of liquids in 1854. His
cramps. She has an Arteriovenous (AV) fistula study of colloids and osmotic forces resulted in
which has a very short segment, insufficient for the ability to separate colloids and crystalloids,
cannulation with two needles. There have been by a process termed “dialysis”, which remains
unplanned hospital admissions with fluid over- the basis for all long-term dialysis technology.
load, and an elective decompression procedure That said, it wasn’t until 1945, when Dr. Willem
for carpal tunnel syndrome. Kolff, from the University of Groningen suc-
What factors need addressing to optimize this cessfully developed an artificial kidney to pro-
lady’s dialysis prescription, and what other prac- vide hemodialysis. Using restricted resources
tical changes might help improve the quality of during the war, he developed a rotating drum
haemodialysis treatment that she receives? kidney to treat a patient with Acute Kidney
Failure. The patient recovered, and lived for
M. Elewa another 6 years, ushering in an era of dialysis
Manchester University Hospitals NHS Foundation for sustaining lives despite kidney failure.
Trust, Manchester, UK Major technological and industrial advances
Ain Shams University, Cairo, Egypt over decades have ensured success of the ther-
e-mail: mohamed.elewa@mft.nhs.uk apy long term and established hemodialysis as
S. Mitra (*) a dominant treatment modality for patients with
Manchester University Hospitals NHS Foundation kidney failure across the globe.
Trust, Manchester, UK
Manchester Academy of Health Sciences Centre,
University of Manchester, Manchester, UK
e-mail: sandip.mitra@mft.nhs.uk
https://doi.org/10.1007/978-3-031-09131-5_17
350 M. Elewa and S. Mitra
Basic Principles of Dialysis solute is swept (“dragged”) across the mem-

brane dissolved in ultra-filtered plasma water”
Diffusion The Convection is necessary to transfer middle
and large molecular solutes that do not transport
…is the net movement of solutes from a region readily by diffusion such as middle and larger sol-
of higher concentration to a region of lower con- utes in uremia. The convective clearance is facili-
centration driven by a gradient in concentration, tated by permeable membranes and pore size
on dialysis, across a semi-permeable membrane distribution of the membrane. Convective proper-
This molecular movement is influenced by the ties of a dialyzer are indicated by its KUF (coeffi-
size of the molecules of the solute (mass) relative cient of ultrafiltration). KUF refers to the
to the size of the pores of the membrane. permeability of the membrane to water or ‘leaki-
Depending on the shape or electrical charge of ness’ of a membrane. A dialyzer and with KUF
the membrane and the molecules, the rate of this >20 mL/h/mmHg is known as high flux dialyzer.
movement across the membrane will be affected. Sieving coefficient of a solute indicates the ease
Diffusive clearance of a dialyzer is measured by with which it can be removed by convection [2].
its KoA or coefficient of mass transfer for urea.
KoA of a dialysis membrane depends on pore
density, pore size distribution, and resistance to Clearance
solute passage. Higher values indicate more effi-
cient dialyzers [1]. Solute removal is measured in terms of clearance.
Dialyzer clearance is “the volume of plasma,
from which a given substance has been removed
Ultrafiltration completely in a given time period”. Urea is con-
sidered a surrogate marker for uremic toxins, and
…is a type of membrane filtration in which has been used for measurement of dialysis effi-
forces, like hydrostatic pressure or concentra- ciency. Urea transport is flow limited, both within
tion gradients (osmotic force) lead to solvent the body and in the extracorporeal system. Within
(e.g. water) moving across a semipermeable the body, urea easily crosses the cell membrane
membrane (between the erythrocyte component and the
Suspended solutes of high molecular weight water component of blood), and with high-
are retained in the so-called retentate, while the efficiency dialyzers, with high mass transfer area
solvent and low molecular weight solutes can coefficient K0A such that extracorporeal clear-
pass through the membrane in the permeate (fil- ance is essentially limited by extracorporeal
trate). Transmembrane pressure (TMP) is the blood (Qb) and dialysate flow rates (Qd). Thus,
hydrostatic pressure gradient across the mem- the major determinants affecting in vivo urea
brane. This is the driving force that causes ultra- clearance in hemodialysis are Blood flow rate
filtration (UF), called hydrostatic (Qb), dialysate flow rate (Qd) and dialyser mem-
UF. Alternatively, if ultrafiltration is induced by brane characteristics [3].
an osmotic force, created by a substance such as
glucose or polymers, it is called osmotic UF.
Components of the Haemodialysis
Machine and Extracorporeal Blood
Convection Circuit
“…is described as solvent drag: if a pressure Extracorporeal Blood Circuit (ECC)

gradient exists between the two sides of a semi-
permeable (porous) membrane, when the A closed extracorporeal system starts from the
molecular dimensions of a solute are such that vascular access, and ensures that the blood is
passage through the membrane is possible, the delivered to the dialyzer and safely back to the
AL GRAWANY
17 Hemodialysis in Clinical Practice 351
Fig. 17.1 Key Components of Hemodialysis Treatment. Diagram illustrating four key components of haemodialysis
treatment: the blood circuit, the dialyser and dialysate delivery system, and the water treatment system
patient. ECC is comprised of a pre-dialyzer limb are fitted in the dialysis machine so that pressure
(arterial) and a post-dialyzer limb (venous). changes, or air can be detected, and when detected
These are manufactured from inert, biocompati- the blood pump would stop, a clamp secures the
ble and sterilized materials. A blood pump pro- venous line to prevent blood return, and the alarm
pels the blood through the tubing system using sound is activated [4] (Fig. 17.1).
negative pressure. The commonest blood pump Pressures in the tubing of the ECC is detected
design is the roller design; rotator rollers com- by transducer devices inside the machine which
press the blood in the tubing system and sweep convert the pressure changes into electronic sig-
the blood towards the dialyzer. The pump speed nals. Transducer protector act as barrier between
is displayed on the machine as Qb (mL/min), and the blood in tube and transducer in the machine.
this can be adjusted, with ranges of up to 500 mL/ If these protector filters are wet, they prevent air-
min. This is automatically calculated from the flow and need to be changed immediately after
number of pump revolutions per minute, and the inspection. The ECC pressures are dependent of
volume of the blood in the tubing system within the blood flow rate and resistance to flow across
the pump. It is important to note that the calcu- the tubing and at the access sites. Pressure
lated Qb could be higher than the actual blood changes will trigger an alarm when it exceeds the
flow rate. This is due to a negative pressure set limits of tolerance in the machine.
exerted by the pump on the tubing system to pro- The arterial pump effect is measured as the
pel the blood. A more accurate measurement is “arterial pressure”, which is a negative value. At
the Effective Blood Flow Rate (EBFR), or cor- pressures −150 mmHg or lower, EBFR deviates
rected Qb for the measured “arterial pressure”. significantly from calculated Qb and can lead to
After the blood passes through the dialyzer, the loss of treatment efficiency. Excessive negative
blood then moves towards the “venous side” of pressures may indicate poor arterial inflow, likely
the circuit, eventually returning back to the due to problematic vascular access. This must be
patient via the AV access. The tubing design addressed to ensure adequate blood flow. High
which has integrated blood chambers and drips, Venous pressures (VP) are caused by an obstruc-
ensures monitoring and safety. These chambers tion distal to the point, kinks in lines or access
stenosis. Low VP caused by poor arterial flow, or concentrate can be tailored to each patient’s
wet venous isolator. A dislodged venous needle needs. The various combinations of fluid con-
may not trigger a venous alarm, hence vigilance centrations may be limited by local guidelines
and adherence to taping policy with a risk mitiga- and availability (Table 17.1).
tion strategy is imperative to avoid exsanguina-
tion. Venous alarms must not be reset without
visual inspection of access site. Ultrafiltration Control Systems
Blood volume monitors are sensors built into
specific blood lines for noninvasive monitoring The goal of ultrafiltration apparatus inside the
of relative changes in plasma volumes by con- HD machine is to ensure precise removal of fluid
tinuously tracking changes in hematocrit or in a safe manner. Ultrafiltration is controlled by
plasma density induced by ultrafiltration. The the means of an ultrafiltration control unit, that
changes can be used to guide ultrafiltration, espe- gets input from the information provided pre-
cially in frequent hemodynamic instability and treatment about desired UF volumes. The unit
intradialytic hypotension [4]. controls the UF rate by means of an UF pump. A
balancing chamber within the machine
(Volumetric Device) adjusts to ensure that dialy-
Dialysate Preparation & Monitoring sate flow to and from the dialyzer is balanced for
accuracy. A Flow Control Device is an alterna-
The purpose of the dialysis circuit or the fluid tive method based on flow sensors on the inlet
pathway within the machine is to prepare the and outlet of the dialyser to achieve accuracy and
dialysate by adding acid concentrate and alkaline balance. The advances in these systems have
buffer to treated water, and deliver it to the dia- enabled large fluid volume shifts across high per-
lyzer at a predetermined rate. It is also designed meable dialysers with relative ease and
to ensure the dialysate has the appropriate com- accuracy.
position, temperature, and pH through a series of
monitors and detectors along the dialysate deliv-
ery system. Finally, the discarded dialysate is Water Treatment Systems
drained along with the excess fluid removed from
the patient through ultrafiltration. For 4 h, thrice weekly standard hemodialysis ses-
The treated water is initially delivered to the sions, an individual patient’s blood comes in con-
dialysis machine, deaerated and warmed, and tact with at approximately 18,000 L of water
moved to the proportioning system. The dialy- per annum at a dialysate flow rate of 500 mL/
sate is prepared here by combining water with min. This underpins the importance of high-
specific portions of acid concentrate (compris- quality standards, adequate water treatment sys-
ing of acetate or citrate with chloride salts of tems, and its effective monitoring in order to
sodium, potassium, calcium, magnesium and ensure patient safety. The water purification sys-
glucose) and bicarbonate buffer solution or tems in use are Reverse Osmosis (R/O) or
powder to produce a physiological solution Deionizer (D/I) systems. The water is “pre-
(final dialysate) which is fed into the dialyser treated” by passing through a series of filters:
inlet to come in contact with blood across the sediment filter, softener, a carbon filter, and
semipermeable membrane. The table below micro-filters. Each of these acts to remove con-
describes the essential safety checks that are taminants, sediments, and minerals. Local guide-
carried out in the prepared dialysate after pro- lines set recommended specification of water
portioning and mixing and prior to it being fed treatment systems and quality, along with the rec-
into the dialyser at commencement of HD. The ommended frequency of monitoring of dialysis
final concentration of electrolytes is generated water. Ultrapure water is defined as water with a
by a process known as proportioning. Dialysate bacterial count below 0.1 colony-forming unit
Table 17.1 Safety measures in the Dialysate circuit
Safety Measure Description Effect

Dialysate temperature: - The dialysis water is warmed inside - Lower dialysate temperature has
the machine with the temperature been associated with lower risk of
control set by the user in units intradialytic hypotension.
typically operating between 35.5-37°C. - The use of dialysate at lower
temperatures (35.5-36°C) during
dialysis proven to improve BP
stability should be balanced against
against patient tolerability.
- High temperatures > 42° C can
cause hemolysis, protein
degeneration and instability.
Dialysate conductivity: - Conductive potential of the fluid - Fluid ionic composition changes will
determined by positively charged trigger alarm.
ions of Na, Ca, K, Mg. The - An empty concentrate jug towards
conductivity measures the rate of end of dialysis a common cause of
flow of an electric current to verify low conductivity.
the concentration of salts in the - Unsafe dialysate will be
solution. Maintained between 12- automatically discarded.
16 mS/cm. - After necessary corrections the
alarm would reset itself.
Dialysate pH: - Dialysate pH recommended 6.8-7.6 - Extremes pH lead to oxidative stress
and checked prior to entry to a and hemolysis
dialyser inlet
Blood leak in dialysate - Photoelectric sensor located - Persistent blood leak alarm requires
detector downstream of the dialyzer outlet, cessation of treatment, discard lines
can detect presence of red cells and and dialyser without washback
trigger an alarm
(CFU)/mL and endotoxin below 0.03 endotoxin from natural materials, they are less biocompat-
unit (EU)/mL and is recommended for use in ible. Biocompatibility can be improved by sub-
hemodiafiltration. This is made feasible by addi- stituting hydroxyl groups, which reduces the
tional highly reliable endotoxin adsorption filters ability of cellulose membranes to activate com-
in the dialysate fluid pathway within the machine. plement and cause leukopenia. Synthetic mem-
branes are more biocompatible and have higher
permeability. Some examples of membrane
Dialyser Membranes and its materials commonly in clinical use include
Performance polysulfone, polyethersulfone, cellulose triace-
tate, polyacrylonitrile, polycarbonate, and
The blood is propelled from the “arterial” side of polymethylmethacrylate.
the circuit towards the hemodialyzer, where the The primary mode of removal of small solutes
dialysis process, an exchange of molecules is diffusion. The rate of diffusion of a solute is
occurs across the dialyser semipermeable mem- dependent on thickness of the membrane, pore
brane, can take place. Most dialyzers available sizes and shape, and diffusivity of the solute. This
today are designed as rigid cylinders, packed is expressed as K0A, and is an in-vitro measure-
with membrane material configured in the form ment provided in specification by manufacturers.
of capillary fibres (Hollow Fibre design). High-efficiency dialyzers can achieve greater
Membranes are either synthetic or non- urea clearances than low flux dialysers at compa-
synthetic. Non-synthetic membranes are derived rable blood flow rates.
The main mode of removal of large solutes, on ferred in acute kidney injury with severe uremia
the other hand, is convection. The ability of a to prevent dialysis disequilibrium syndrome,
larger solute to pass through the pores of a mem- whilst large surface area dialyzers are indicated
brane is expressed as the sieving coefficient of in the treatment of poisoning, drug overdose and
the membrane for a given solute. Dialyzer manu- toxicity [1].
facturers provide sieving coefficients of albumin,
B12, beta-2 microglobulin and others, as a mea-
sure of convective performance. Hemodialysis Techniques
The ultrafiltration coefficient (KUF) is a mea-
sure of the water permeability of a membrane, Three principle hemodialysis techniques are used
and values above 20 mL/h/mmHg indicate high in clinical practice (Table 17.2).
flux dialyzers which can readily move large vol- Hemodiafiltration may be considered as a
umes of fluid at low transmembrane pressure gra- treatment for intra-dialytic hypotension refrac-
dients. A dialyzer with higher KUF will typically tory to other measures, and for dialysis patients
have higher diffusive and sieving coefficient with favorable prognosis who are unable or
values. unlikely to be transplanted. There has been a
Majority of international guidelines recom- growth in the use of HDF as a treatment modality
mend the use of high flux, high efficiency dialyz- and is recommended for consideration for
ers and Information about membrane properties Incentre and satellite hemodialysis by NICE, UK
is provided by manufacturers. For intensive care (2019). Further evidence generating studies in
units, small surface area dialyzers may be pre- HDF are ongoing [5].
Table 17.2 Hemodialysis Techniques (Mitra & Elewa 2021)
Haemodialysis Technique Description
Conventional • The setup allows blood flow into a dialyser compartment, and the dialysate flow
Hemodialysis in the other compartment, in opposing direction to maximize solute movement
(Low Flux or High Flux using a low or high flux dialyser acting as the interface membrane. High flux
Membrane) hemodialysis, predominantly a diffusive treatment combined with limited
volumes of convective clearances.
Hemodiafiltration • Hemodiafiltration (HDF), combines both diffusive and high dose convective
(with an additional HDF therapy.
pump and reinfusion) • Newer technology has enabled ultrapure replacement solution to be generated
and delivered by the device (on-line HDF), allowing higher convective volumes
and easier delivery of this therapy to patients.
• A large convective volume creates a solute drag for middle and large middle
molecules, the convective volume replaced by reinfusion of online generated
substitution fluid or using packaged solutions by a separate HDF pump for
reinfusion.
• The volume control is achieved by balancing the rate of fluid replacement using
precise volumetric devices with in the machine.
Expanded Hemodialysis • Expanded HD (HDX) define a treatment where diffusion and convection are
(Using a dedicated technically integrated inside a hollow-fiber dialyzer equipped with a medium
membrane) cut-off membrane (MCO) without the need for substitution fluid.
• The MCO Dialyzer, through its innovative design, combines the functional
features of enhanced permeability, increased selectivity, controlled retention,
and improved internal filtration into a single dialyzer, enabling removal of
small, conventional middle molecules and large middle molecular uremic
toxins without the need for additional pump or reinfusion fluid.
Prescribing Hemodialysis Anticoagulation in Haemodialysis
Standard Prescription As the blood moves through the extracorporeal

circuit, it is exposed to surfaces of varying throm-
bogenicity. Anticoagulation is therefore essential
Practice Point 1
to prevent the formation of microthrombi, or
The standard hemodialysis prescription blood coagulation which can result in circuit loss.
should include: The formation of microthrombi in the dialyzer
causes partial clotting of the membrane pores,
• Dialyzer (material, surface area, flux) reducing the effective membrane surface area,
• Modality (e.g., HFD, HDF predilution, reducing dialysis efficacy.
HDF post dilution) Clinical practice guidelines on anticoagulation
• Dialysate concentrate composition. in hemodialysis published by professional societies
• Dialysate flow rate are provides the best practice guidance. Practice
• Dialysate temperature, Conductivity, should be defined by Unit Protocol along with
Bicarbonate instructions for reversing anticoagulation as
• Blood flow rate required. The use of either unfractionated heparin,
• Ultrafiltration volume and rate or low molecular weight heparin is the mainstay in
• Treatment Time HD. Regional citrate recommended in situations
• Access Connection: Needle gauze, with high bleeding requires expertise and is rarely
Connection (SNHD, reverse) Catheter practiced in chronic HD. Use of high blood flow
Locks rates with frequent saline flushes could reduce anti-
• Anticoagulation (anticoagulant, coagu- coagulation requirement significantly particularly
lopathy, monitoring) for shorter duration sessions. In patients with HIT
• Medications to be administered. (heparin induced thrombocytopenia) danaparoid,
• Specific blood tests or monitoring direct thrombin inhibitors or regional citrate are rec-
required. ommended [6]. Systemic anticoagulation should be
• Special Instruction for Nurses (Access avoided in the presence of active bleeding. Minimal
issues, Post HD instructions) anticoagulation protocols must be applied in spe-
• Any limitations to be considered e.g., cific settings.
timing, logistical constraints,
preferences
Practice Point 2
Signs of clotting in the extracorporeal

circuit include:
The prescription of dialysis should take into
account patient characteristics such as predial- • Raised venous pressure
ysis clinical observations such as blood pres- • Reduced arterial pressure
sure, temperature and oxygen saturation, new • Raised trans membrane pressure (TMP)
onset symptoms, glycemic and electrolyte sta- • Visible signs of clotting, streaky
tus. Particular attention to predictable rapid dialyser
changes in weight as a result of illnesses or
recent hospitalization would improve accuracy
of the ultrafiltration prescription. All these fac-
tors enable the clinical staff to individualize cute Heparin Free/Minimal
A
the treatment to changes in patient health Anticoagulant Dialysis
status. In patients with acute trauma, clotting disorders,
active bleeding, or in the immediate pre- or post-
operative period (in a 12 h window), anticoagu- or alteration in appetite can all lead to changes
lant free dialysis should be performed. Sodium in target weight. Target weights should be
chloride 0.9% 200 mL boluses may be used if reviewed ideally on a monthly basis.
required [6]. Higher blood flow rates are effective
in reducing need for anticoagulation. Outside
these settings, where circuit is unstable with Connecting and Commencing
clots, a minimal dose of heparin/LMWH may be Treatment
considered after discussion with nephrologist or
hematologist. A single HD treatment is initiated with a disin-
Circumstances when HD with minimal or fection cycle in the machine, mixing of the dial-
heparin free anticoagulation may be required ysate and a compulsory test program. Once this
is complete the machine is setup with blood
lines and dialyser followed by priming to de-
Practice Point 3
aerate and adjust the bubble trap levels.
Heparin free dialysis may be necessary if: Following this the treatment and machine set-
tings are entered followed by preparing the anti-
• Active bleeding or clinically suspected coagulation and cannulation of the vascular
active bleeding access using an appropriate needle gauge and
• Immediate preoperative period (within aseptic non touch technique. The Arteriovenous
12 h of surgery) Fistula (AVF) anatomy and examination charac-
• Immediate post-operative period (12 h teristics determine the choice of the needle
post-surgery) gauge and the optimal cannulation technique.
• 12 h before and after invasive tests The cannulated access is then connected to the
(angiogram, biopsies) blood lines and the treatment initiated.
• Therapeutic anticoagulation with UFH /
LMWH for other conditions
• Severe blood dyscrasias or bleeding Optimizing Dialysis Prescription
diathesis
• Acute trauma The use of wider needle gauge, higher blood
flows, efficient dialysers with high permeability,
optimum anticoagulation and the prescribed time
are key factors in driving optimal clearances for
ltrafiltration (UF) and Residual
U both diffusion (urea Kt/V) and convection (high
Renal Function (RRF) substitution volumes) in a standard HD or HDF
treatment. In selected individuals, less frequent,
Careful assessment of volume status, with revi- incremental or shorter sessions can be provided
sion of target weight is needed, to tailor UF pre- in presence of residual renal function, or to
scription accordingly. Assessment of volume achieve better quality of life when longevity is
status may be aided with static measurements not a prime target. HD therapy is often tailored to
of fluid compartments using bioimpedance patients’ needs provided it is safe and adequate
devices or with more dynamic real time assess- for the individual.
ment of changing relative blood volume (RBV)
during ultrafiltration using blood density or
hematocrit monitoring (blood volume moni- Other HD Techniques
tors). Large registry dataset analysis has dem-
onstrated that high ultrafiltration rates (>12 mL/ Isolated Ultrafiltration (Iso UF)
kg/h) are associated with adverse cardiovascu-
lar outcomes and should be avoided [7]. Iso UF mode is used when rapid ultrafiltration is
Underlying illnesses, hospitalization, cachexia required, typically in emergencies such as pul-
monary oedema. The dialysate delivery is in the dialyzer, and the venous pump pushing blood
bypass mode, and the transmembrane pressure back to the patient. This happens in sequence, to
is generated by negative pressure in the dialy- allow both outflow and inflow via a single needle.
sate compartment. Iso UF rates deployed are The effective blood flow cannot exceed 300 mL/
typically 1 L per hour but this may be varied. min. Major drawbacks include recirculation and
Hemodynamic stability is often better main- reduced dialysis efficiency. Some advantages of
tained in the absence of circulating dialysate SNHD include the ability to use an inadequate
fluid whilst rapid ultrafiltration is achieved. fistula with limited access (repair, infiltration,
Lack of blood contact with dialysate during Iso short segments) or maturing access reducing
UF prevents diffusion and thereby achieves no puncture-related pain, stress and complications
net solute removal. The time spent on Iso UF by avoiding double puncture [8]. Other modes
will achieve fluid removal only but no solute that can be used include sustained low efficiency
removal, hence the process must not be consid- dialysis (SLED), and profiled dialysis. SNHD
ered as dialysis time. reduces the risk of significant blood loss in the
event of a needle dislodgement, as the blood
pump would automatically stop, protecting
achine in Bypass and Recirculation
M against ongoing blood loss. Patients on Frequent
Mode Nocturnal HD often use this mode for routine
treatment.
The dialysis machine is specifically configured
to allow the dialysate fluid to bypass the dialy-
ser and be discarded to waste (Machine in Dialyser Reuse
Bypass). This is a potential safety feature for
unsafe dialysate to be spent without coming in Hemodialyzer reuse refers to the practice of
contact with blood and harming the patient. The using the dialyzer multiple times for a single
same mode of bypass is activated to perform patient. The process, with the right implementa-
Isolated Ultrafiltration. The bypass mode is tion, is potentially a safe and cost-effective pro-
also utilized to disconnect the blood circuit cedure for high-flux dialyzers. However, there
from the patient and allow the extracorporeal has been a steady decline of this practice in the
blood volume to recirculate only for a limited United States and Europe since late 1990s par-
period of time (5–20 mins). This option allows ticularly since the introduction of regulatory
the patient to have a temporary disconnection label of “single use only” for dialysers. The
from dialysis to reposition access needles or practice is still prevalent in some countries.
troubleshoot any patient issues without disman- Dialyser reprocessing is essential to render it
tling the whole setup and circuit. Extracorporeal safe with a membrane surface suitable for con-
recirculation of blood beyond a limited time tact with blood. Dialyser reuse involves several
period risks alteration in the composition of step processes of rinsing, cleaning, performance
blood which may be unsafe to return back to the testing, and disinfection of dialyzers prior to
patient. reuse and requires systems in place for its moni-
toring. The process requires the use of cleaning
and germicidal agents that are potentially toxic,
Single Needle Hemodialysis (SNHD) and accidental contact with these agents may
expose both patients and dialysis staff to health
Once a popular option, especially in Europe, the hazards [9]. Rigorous quality assurance proce-
single needle dialysis lost its popularity in the dures need to be in place to monitor the proce-
eighties. In single needle hemodialysis, a specific dures for flushing and testing dialysers, patient
double pump facility must be available in the specific dialyser usage and verification proce-
machine, which propels the blood through the dures for “volume pass” and “reuse number
tubing, with the arterial pump delivering blood to pass” [10].
Home Hemodialysis Buttonhole Cannulation
Maintenance dialysis patients who receive in-center

Practice Point 4
dialysis thrice weekly have to endure an extended
72-hr interdialytic gap during the weekend, which The advantages and disadvantages of but-
has been strongly linked with higher hospitaliza- tonhole cannulation
tions and increased risk of mortality. Avoidance of a Advantages:
long gap through an alternate day dialysis schedule
or extended dialysis regimen of more frequent dial- • Helpful in needle-phobic patients
ysis, or intensive HD, can most feasibly be deliv- • Reduce cannulation attempts
ered in the Home setting. The avoidance of regular • Reduce aneurysms & aneurysm size
trips to hospital for dialysis may also be advanta- • May be less painful
geous for convenience and lifestyle reasons. The • Helpful when a narrow segment avail-
adaptive dialysis regimen at home often allows able to needle
patients more liberty with dietary and fluid restric- • Fewer hematomas
tions positively impacting on quality of life.
Poor prognosis outcome indicators such as Disadvantages:
high interdialytic fluid gains, refractory hyper-
tension, hemodynamic instability and severe • Association with higher infection rate
hyperphosphatemia can be more effectively man- • May require re-siting
aged through extended dialysis in the home set-
ting. Home HD also alleviates strain on available
capacity and workforce benefitting the provider
and the health system overall. It is therefore a key Haemodialysis Governance
recommendation with a call to action to offer the and Quality Assurance
choice of Home HD to Incentre Dialysis patients.
The key barriers to a successful home HD Treatment safety in HD is a broad concept and
transition are available space at home, needle entails not only preventing clinical and mechani-
phobia, lack of support at home and treatment cal complications during treatment, but also
burden. Barriers can be overcome with specific ensuring patient and staff safety, robust infection
clinical strategies e.g., use of blunt needles for control measures, and continued quality assur-
Button-Hole cannulation to overcome needle ance. This requires a multidisciplinary team in
phobia where clinically appropriate. order to cover the various aspects of dialysis care.
A successful Home program is driven by a Errors in HD can cause harm and fatality.
dedicated patient training program, a robust Although an in-center dialysis facility is a health
home support system and clinical leadership care provider; management of dialysis unit
from the multidisciplinary team members. encompasses a lot more than just dialysis
Several HD modalities (Table 17.3) may be provision.
offered in the home setting to fit in with patient The Medical Director is primarily responsible
preferences and lifestyle but each will require for the quality assessment and performance
adjustments to prescription accordingly. For improvement programs within the facility. An
example, in comparison to a Incentre session, a administrator is responsible for fiscal manage-
Nocturnal dialysis session with longer hours, will ment, staff training and coverage. Physicians,
require lower blood flow rates, more anticoagula- Nurse in charge, Nursing staff, Support workers,
tion to avoid circuit loss, dialysate settings suitable Technicians, Dietitian, and Social worker com-
for longer hours, and specific interventions such as prise a multidisciplinary team within a facility,
appropriate supplementation of water-soluble vita- working together to improve system process and
mins and where necessary, dialysate phosphate clinical outcomes through quality assurance.
supplementation for hypophosphatemia [11]. Attention should also be paid to the physical
Table 17.3 Different Modalities for Home HD [12]
Modality Prescription parameters Key Points

Short Daily HD 2-3 hours, 5-7x/week • RCT evidence of benefit (FHN Study)
(SDHD) Bicarbonate mmol/l 32-36 • Can be accommodated in the day for patients who work.
Qb ml/min 350-400 • Effective in high fluid gains and heart failure
Qd ml/min 300-600 • Fluid gain between treatments is less; however, with shorter
treatment times, UF rate per hour may be too high
• Greater use of consumables & storage requirements
Nocturnal HD 6-8 hours, 4-6x/week • Keeps patients free during the day, allows for more liberal diet
(NHD) including alternate nights. • Enhanced phosphate and middle molecule removal
Bicarbonate mmol/l 28-35 • Phosphate supplementation may be required in 20 %
Qb ml/min 200-300 • Can disrupt sleep and patients may fear needle dislodgement.
Qd ml/min 300-400 • Greater loss of water -soluble vitamins. Routine replacement of
vitamins C, B and folic acid recommended.
Alternate daytime HD 4-6 hours, alternate days • Avoid long interdialytic gap, allows dialysis free days in the
(ADHD) Bicarbonate mmol/l 28-35 week
Qb ml/min 300-400 • Most popular regimen with HHD patients
Qd ml/min 300-600 • Minimal increase in consumables
• Lack of published research in this modality
Conventional HD 4-5 hours, 3/week • Often used in those who do not wish to consider more
Bicarbonate mmol/l 32-36 frequent schedules
Qb ml/min 300-400 • Compared with in-centre HD may have an added benefit
Qd ml/min 500-800 associated with patients performing their own treatment at
home
• More flexibility with timings compared in-centre HD, saved
travel time
• Excellent initial regimen for units new to home HD while
experience is gained
Hemodiafiltration at Conv, SDHD, ADHD, NHD • Can be performed with ultrapure water
Home Prescription Identical to • Enhanced larger middle molecule clearance.
above • High convective volumes associated with clinical outcome
benefits may be more readily achieved
Low Flow Dialysate SDHD or NHD or Alt day • No comparative study between high and low flow dialysate HD
HD systems Lactate mmol/l 40-45 systems
Qb ml/min 300-500 • Can achieve similar Kt/V with extended time and frequency.
(20-60 L dialysate per Qd ml/min 90-300 (NHD) • Not suitable for thrice weekly schedule
treatment) 80-160 (SDHD) • Portability options-an advantage for some patients
environment such as equipment standards, fire

safety, patient care settings, water quality, and Practice Point 5
infection control measures. Several standard and Common, potentially avoidable adverse
quality metrics are being used to report quality events in HD facility [15]
and performance improvement. These are either
Process metrics (such as targets for dialysis ade- • Needle dislodgements and catheter
quacy, vascular access, hemoglobin, infection disconnection
rates, immunizations) or Outcome measures • Hygiene lapses
(mortality, hospitalization, transplant rates, qual- • Access related blood stream infections
ity adjusted life years and patient experience). An • Access infiltrations
embedded facility culture of incident reporting of • Medication errors
adverse events and “near misses” supported by • Errors at Care transitions
Root Cause Analysis (RCA) is essential to good • Patient falls
governance and safety for staff and patients [13, • Adverse clinical incidents with disasters
14] (Fig. 17.2). (water failures, outage)
• A medical director Both answer to a governing body; which adopts and enforces
• A facility administrator rules relative to, health care and safety of patients, patients'
personal and property rights, health care and safety.
Personnel • Nurse in charge • Technicians
• Nursing staff • Dietitian
• Support workers • Social worker
Physical Attention should be paid to the physical environment of the facility. This includes equipment,
environment fire safety, patient care settings, water quality, and infection control measures.
Several standard and quality metrics are being used to measure quality and promote
Quality performance improvement:
Process metrics: dialysis adequacy, vascular access (AVF vs graft vs lines), target hemoglobin, infection rates,
Improvement Immunizations, etc.
measures Outcome measures: mortality, hospitalization, and transplant rates, quality adjusted life years, patient safety and
patient satisfaction
Fig. 17.2 Managing a Dialysis Facility. Diagram illustrates the elements recommended to manage a dialysis facility;
divided into three domains: personnel, physical environment and quality improvement measures
ersonalized Dialysis: Future

P level and in programs to standardize and improve
and Emerging Opportunities efficiency. Ultimately, precision dialysis therapy,
will become more feasible as we better under-
Research and innovation in biomaterials, sensors stand biological, behavioral and social determi-
and engineering, provides the opportunity to nants of good health in dialysis [16].
potentially disrupt and advance technology in
dialysis. There has been an intense focus on
enhancing dialysis by creating miniaturized, por- Conclusions
table, wearable and implantable devices to poten-
tially improve both blood purification and patient The 65 year old HD patient discussed at the
experience. In modern devices, predictive algo- beginning of the chapter highlights the impor-
rithms allow adaptation in real time to allow bio- tance of good dialysis practice and high quality
feedback of ultrafiltration rate in response to blood purification. She is anuric and perhaps
changing blood volume parameters to improve not receiving adequate blood purification for
hemodynamic and volume management. both small and middle molecules (e.g predialy-
Applications of Artificial Intelligence (AI) in sis hyperkalemia and carpal tunnel syndrome).
dialysis can further improve treatment safety, The dialytic clearance can be augmented by
troubleshoot dialysis delivery, preemptive man- strict adherence to the dialysis prescription and
agement and personalized treatment to promote HD prescription changes as discussed in this
good health in dialysis. AI algorithms may also chapter. Prescription considerations should
address real time monitoring of vascular access include higher blood flows, improved antico-
and its patency. agulation regimen and enhancing convective
Advanced technology must include assess- clearances, through increasing dialysis time or
ments of care, enhanced monitoring, and enabling adding haemodiafiltration mode or expanded
independence, efficiency and safety but also aim hemodialysis, if available. Reducing interdia-
to reduce burden for staff and patients. Big data lytic weight gain and limiting the rate of ultra-
analytics can be applied both at an individual filtration will improve fluid related
AL GRAWANY
complications. Button hole cannulation may be 2. The signs that indicate excessive clotting in
considered to allow use of short segment AVF, circuit during treatment are:
to achieve higher blood flows and mitigate A. Raised venous pressure
against future catheter related complications. B. Reduced arterial pressure
Extended dialysis, ideally in the home settting, C. Raised trans membrane pressure (TMP)
could improve adherence, resolve many of the D. Visible signs of clotting, streaky dialyser
restrictions of incentre HD, and potentially E. Low dialysate conductivity
improve cardiovascular outcomes. Correct answer (A, B, C, D)
Since its inception nearly six decades ago, 3. Indicate which of these factors will not trig-
Hemodialysis therapy for clinical use, has under- ger alarms for High venous pressures
gone a massive technological progress led by A. Blood Circuit connection error
unprecedented engineering advances and entre- B. AVF stenosis
preneurship. Fundamentally, the current dialysis C. Kink in the blood tubing, returning
machine is not dissimilar to the early models set limb
up by the forefathers of modern dialysis, and con- D. Kink in blood tubing pre dialyser
stitutes, a blood circuit, a dialyzer and the dialy- E. Occluded venous limb of dialysis
sate pathway with precise control systems to catheter
ensure safety. Further advances have led to Correct answer (A, D)
increased safety, tolerability, and greater efficacy 4. Disconnection haemorrhage from a catheter
and flexibility of treatment. The efficacy of the can be prevented by
treatment, however, is still critically reliant on a A. Keeping access site visible at all time
reliable access to the bloodstream and an effec- during a treatment
tive anticoagulation regimen to maintain extra- B. Adherence to a Safe Taping policy
corporeal patency and blood flow. C. Optimum securement of the lines
Hemodialysis therapy remains one of the D. A robust HD governance structure
greatest technological inventions in modern med- E. Specific modules incorporated in staff
icine and the cornerstone therapy for sustaining competency training and assessment
human lives afflicted by kidney failure. The Correct answer (A, B, C, D, E)
improvements in HD safety and technology have 5. Which of these constitute good practice in
seen an unprecedented uptake and increase in HD Ultrafiltration?
prevalence. Further innovation is necessary to A. Limit Interdialytic weight gain to 3%
improve patient experience, outcomes and qual- body weight
ity of life on dialysis. B. UF rate should vary between 10–20 mL/
kg/h
C. Empower patients with knowledge on
Questions fluid balance
D. Reassess target weight on a monthly
basis
1. The single most effective means of increasing E. Use relative blood volume monitoring
diffusive clearance of small solutes during for unstable patients
HD such as in Predialysis Hyperkalemia is: F. Use Iso UF regularly for fluid overload
A. Increasing Dialysate flow rate Correct answer (A, C, D, E)
B. Increase Dialyser Size 6. The following are some clinical features of
C. Administer Insulin dextrose middle molecule toxicity
D. Increasing haemodialysis machine blood (Residual syndrome)
flow rate A. Macroglossia
E. Increasing Time on dialysis B. Arthropathy
Correct answer (D) C. Haemochromatosis
D. Carpal Tunnel syndrome References

E. Neuropathy
Correct answer (A, B, D, E) 1. Haroon S, Davenport A. Choosing a dialyzer:
what clinicians need to know. Hemodial Int.
7. Convective clearances can be augmented in 2018;22(S2):S65–74.
Haemodiafiltration by the following 2. Khan MA, Hussain A. Hemodialysis membranes: a
A. Switch from 15 g to 16 g needles for review. J Membr Sci Technol. 2019;9:199.
cannulation 3. Eloot S, Schneditz D, Vanholder R. What can
the dialysis physician learn from kinetic model-
B. Use of higher surface area dialysers ling beyond kt/v urea? Nephrol Dialysis Transpl.
C. Adequate Anticoagulation 2012;27(11):4021–9.
D. Higher blood pump speeds 4. Mitra S, Mitsides N. Technical aspects of hemodialy-
E. Increased treatment time sis. Core concepts in dialysis and continuous thera-
pies; 2016, pp. 15–26.
Correct answer (B, C, D, E) 5. Canaud B, Busink E, Apel C, Bowry SK. Is there not
8. Expanded HD therapy delivers improved sufficient evidence to show that haemodiafiltration
dialytic toxin clearances on middle and large is superior to conventional haemodialysis in treat-
middle molecules through the use of: ing end-stage kidney disease patients? Blood Purif.
2018;46(1):7–11.
A. Large surface area dialysers 6. Cronin RE, Reilly RF. Unfractionated heparin for
B. High pore density dialyser hemodialysis: still the best option. In: Seminars in
C. Homogenous dialyser pore size dialysis, vol. 23. Oxford: Blackwell Publishing Ltd.;
distribution 2010. p. 510–5, No. 5.
7. Assimon MM, Flythe JE. Rapid ultrafiltration rates
D. Substitution fluid and additional pump and outcomes among hemodialysis patients: re-
E. HD machine special design and examining the evidence base. Curr Opin Nephrol
adaptation Hypertens. 2015;24(6):525–30.
Correct answer (B, C) 8. Vanholder R. Single needle hemodialysis: is the past
the future? J Nephrol. 2020;33(1):49–58.
9. Advantages of Button-hole cannulation strat- 9. Upadhyay A. Dialyzer reuse: is it safe and worth it?
egy for AVF include Brazil J Nephrol. 2019;41(3):312–4.
A. needling short AVF segments 10. Lowrie EG, Li Z, Ofsthun N, Lazarus
B. lower risk of infections JM. Reprocessing dialysers for multiple uses: recent
analysis of death risks for patients. Nephrology
C. addressing needle phobia Dialysis Transplantation. 2004;19(11):2823–30.
D. requires skilled expertise and resiting 11. Young BA, Chan C, Blagg C, Lockridge R, Golper
E. use of sharp needles in a preformed track T, Finkelstein F, et al. How to overcome barriers and
to alleviate pain establish a successful home HD program. Clin J Am
Soc Nephrol. 2012;7(12):2023–32.
Correct answer (A, C) 12. Mitra S, Kharbanda K. Home haemodialysis and hae-
10. The key clinical indications for recommend- modiafiltration. IntechOpen; 2016.
ing extended HD at Home are 13. Himmelfarb J, Kliger AS. End-stage renal dis-
A. Persistent fluid overload and ease measures of quality. Annu Rev Med.
2007;58:387–99.
hypertension 14. Blankschaen SM, Saha S, Wish JB. Management of
B. High interdialytic weight gain and ultra- the hemodialysis unit: core curriculum 2016. Am J
filtration rate Kidney Dis. 2016;68(2):316–27.
C. Dialysis via Catheter 15. Garrick R, Kliger A, Stefanchik B. Patient and facility
safety in hemodialysis: opportunities and strategies to
D. Uncontrolled anemia develop a culture of safety. Clin J Am Soc Nephrol.
E. Severe LVH (increased LV mass) 2012;7(4):680–8.
Correct answer (A, B, E) 16. Burlacu A, Iftene A, Jugrin D, Popa IV, Lupu
PM, Vlad C, Covic A. Using artificial intelligence
resources in dialysis and kidney transplant patients: a
Test your learning and check your understand- literature review. BioMed Res Int. 2020, 2020;
ing of this book’s contents: use the “Springer
Nature Flashcards” app to access questions
using https://sn.pub/cz9Cok. To use the app,
please follow the instructions in Chap. 1.
Complications of Haemodialysis
18
Oluwatoyin I. Ameh, Udeme E. Ekrikpo ,
Aminu K. Bello , and Ikechi G. Okpechi
Clinical Scenario How would you manage this patient acutely,

You are called to assess an unwell 67-year-old and what further information would help estab-
male with End Stage Kidney Disease (ESKD) lish the cause of his presentation?
secondary to hypertensive nephropathy on the
haemodialysis unit. On initial assessment, he is
dialysing via a native left brachiocephalic arterio- Introduction
venous fistula: he is conscious, with a GCS of
15/15, but is pale, clammy and cool to touch. He Worldwide, haemodialysis (HD) is the common-
has a blood pressure of 80/60 mmHg and a pulse est form of kidney replacement therapy (KRT),
of 115 beats per minute. His oxygen saturations and can be associated with various complications
are 98% on air. His blood glucose is 7 mmol/L; related to uremia, vascular access, fluid and elec-
he has no concurrent chest pain, and his ECG trolyte management, as well as increased poten-
shows a sinus tachycardia, with voltage criteria tial for bleeding due to use of anticoagulation.
for left ventricular hypertrophy. Progressive loss of kidney function leads to a
uraemic state, associated with accumulation of
fluid, acid-base disorders, multi-organ dysfunc-
O. I. Ameh
Division of Nephrology, Zenith Medical & Kidney tion, and retention of various solutes.
Centre, Gudu, Abuja, Nigeria Haemodialysis can be used to correct several of
U. E. Ekrikpo these abnormalities, but can cause problems
Renal Unit, Department of Internal Medicine, related to technique, frequency or other patho-
University of Uyo, Uyo, Nigeria physiological processes occurring. For instance,
A. K. Bello repeated needling of a fistula can lead to aneurys-
Division of Nephrology and Immunology, Faculty of mal dilatation, rupture and severe bleeding
Medicine and Dentistry, University of Alberta, requiring transfusion, hospitalisation or death.
Edmonton, AB, Canada
e-mail: aminu1@ualberta.ca Similarly, anaemia may be worsened by repeated
blood loss due to clotting of the dialysis line.
I. G. Okpechi (*)
Division of Nephrology and Immunology, Faculty of Although most HD complications occur acutely
Medicine and Dentistry, University of Alberta, (e.g. seizures, febrile episodes, etc), others are
Edmonton, AB, Canada insidious and take to develop and diagnose (e.g.
Division of Nephrology and Hypertension, Kidney dialysis-related dementia). In this chapter, we
and Hypertension Research Unit, University of Cape present an overview of common complications
Town, Cape Town, South Africa associated with HD with available treatment
e-mail: ikechi.okpechi@uct.ac.za
https://doi.org/10.1007/978-3-031-09131-5_18
364 O. I. Ameh et al.
options. Complications of continuous ambula- ume that has to be removed within a time con-
tory peritoneal dialysis (CAPD) are discussed in straint of usually 4 h. Normally in the setting of
a separate chapter. volume loss, cardiovascular and neurohormonal
mechanisms are activated, including: increased
heart rate and myocardial contractility, increased
Cardiovascular Complications peripheral resistance and activation of the sym-
of Haemodialysis pathetic nervous system and the renin angioten-
sin aldosterone system. These all promote
Intradialytic Hypotension plasma refilling, and thereby maintain intravas-
cular volume and BP. With intradialytic hypo-
Definition of intradialytic Hypotension [1, 2]: tension however, certain procedure-related and/
Intradialytic hypotension was defined by KDOQI in
2005 as a reduction in systolic blood pressure (SBP)
or patient-related factors lead to ineffectual
≥20 mmHg or a reduction in mean arterial pressure responses with resulting hypotension (Fig. 18.1).
(MAP) by 10 mmHg with associated symptoms of Dialysis-related factors usually include dialy-
cardiovascular (CV) compromise such as dizziness, sate composition (low sodium, low calcium),
nausea, vomiting, deep sighing or yawning [1]. More
recently, KDIGO proposed in 2020 this be amended to
use of warm dialysate, acetate dialysate buffer,
“Any symptomatic decrease in SBP or a nadir aggressive ultrafiltration, and low plasma osmo-
intradialytic BP <90 mmHg should prompt lality. Large interdialytic weight gain, pre-dialy-
reassessment of BP and volume management [2]” sis use of antihypertensive medications,
ingestion of meals during dialysis sessions
Intradialytic hypotension is prevalent in (leading to significant splanchnic bed pooling of
between 15 and 50% of dialysis sessions, blood volume), hypoalbuminemia, pre-existing
depending on the case definition criteria comorbidities (e.g. pericardial effusion, periph-
employed [2, 3]. Pathophysiologically, it is a eral vascular disease, autonomic dysfunction in
maladaptive response to the acute and appar- diabetic patients) are all examples of patient-
ently fixed fluid (water) shifts that occur during related factors that are associated with intradia-
a dialysis session i.e. a target ultrafiltration vol- lytic hypotension.
Cardiac factors
– Myocardial infarction
– Arrhythmias
– Pericardial tamponade
– Structural heart disease
Air embolism Impaired

vasoconstriction
Patient-related factors:
– Use of antihypertensive drugs Dialysis-related factors:
– Anaemia
– Diabetes with autonomic neuropathy
Intradialytic – Use of acetate dialysate
– Low dialysate sodium
– Food ingestion (splanchnic vasodilation) hypotension – Low dialysate calcium
– Ongoing infection (sepsis) – Generation of cytokines (e.g., NO, IL-1)
– Increase in core body temperature (fever)
Dialyzer
reaction Hemolysis
Reduced effective circulating volume:

– Haemorrhage
– Excessive fluid removal
Fig. 18.1 Factors contributing to intradialytic hypotension.

NO Nitric oxide, IL-1 Interleukin-1
18 Complications of Haemodialysis 365
The acute management of symptomatic intra- function due to repeated kidney parenchymal
dialytic hypotension episodes is dictated by the ischaemia (Fig. 18.2).
severity of each episode and can entail postural Given the serious consequences, preventive
adjustments to improve venous return (e.g. the strategies must be implemented in the HD patient
Trendelenburg position), stopping ultrafiltra- who suffers repeated episodes of intradialytic
tion—with or without terminating the dialysis hypotension: First line preventive measures, as
session altogether, and the administration of outlined by the European best practices guide-
intravenous fluid and oxygen. lines [8], include dietary sodium restriction,
There are long term sequelae to repeated intra- bicarbonate buffer use, a clinical reappraisal of
dialytic hypotension. Hence, this should be mini- patient’s dry weight, adjusting dialysate tempera-
mised in HD patients, as it portends adverse ture to 36.5 °C, avoiding meals during dialysis,
morbidity and mortality outcomes. The conse- and adjusting the doses and timing of administra-
quences of repeated intradialytic hypotension tion of antihypertensive medication. In more
includes repeated myocardial stunning with refractory cases, Midodrine—a selective alpha-1
resultant myocardial fibrosis and cardiac hyper- adrenoceptor agonist—may be used, and l-
trophy [4, 5], endotoxin translocation due to gut carnitine supplementation is also advocated. If all
ischaemia associated with chronic systemic measures are unsuccessful, the patient may ben-
inflammation [6, 7], and loss of residual kidney efit from a change in dialysis modality.
• Myocardial stunning
• Vascular access
• Myocardial fibrosis
thrombosis
• Cardiac hypertrophy
• Gut ischaemia • Repeated kidney

associated with parenchymal
chronic systemic ischaemia leads to
inflammation leads loss of residual
to Endotoxin kidney function
translocation
Fig. 18.2 Consequences of Intradialytic Hypotension

Intradialytic Hypertension identified and include a chronically expanded

extracellular volume, osmolality shifts and endo-
Definition of intradialytic Hypertension [2]: thelial cell dysfunction. Chronic extracellular
Intradialytic hypertension has not hitherto been defined
in international consensus guidelines, although KDIGO
volume overload has consistently been demon-
recently proposed in 2020 a definition of: “An SBP rise strated in patients with intradialytic hyperten-
>10 mmHg from pre- to post-dialysis in the sion. Paradoxically, these patients weigh
hypertensive range in at least 4 of 6 consecutive relatively less, have smaller interdialytic weight
dialysis treatments should prompt a more extensive
evaluation of BP and volume management, including
gains and have relatively lower pre-dialysis BP
home and/or ABPM [2]”. readings [12]. They however, have a higher post-
dialysis extracellular water-to-total body water
Whilst haemodialysis is physiologically more ratio (ECW/TBW) despite adequate ultrafiltra-
likely to lead to a fall in BP, in a subgroup of tion volumes. Ultrafiltration goals in HD are usu-
patients, a paradoxical increase in BP is recur- ally dictated by the acute ECW gain in the
rently observed during most treatment sessions. inter-dialytic period and not the overall ECW
Intradialytic Hypertension has hitherto variously gain over time and as such, in intradialytic hyper-
been classified as an increase in mean arterial tension there is a persistence of extracellular
pressure (MAP) of >15 mmHg during a treat- space overload. This is the rationale for ultrafil-
ment session or shortly after a session, or as tration probing as a management strategy in
hypertension occurring in the second or third intradialytic hypertension (see below).
hour of dialysis treatment following substantial As previously discussed under intradialytic
ultrafiltration, and as a pre- to post-dialysis hypotension, serum osmolality changes due to
increase in SBP of 5–10 mmHg [9]. KDIGO’s solute shifts during dialysis usually cause a BP
has recently issued a statement defining it as an decline. However, in patients with recurrent
SBP rise >10 mmHg from pre- to post-dialysis in intradialytic hypertension, the gradient of solute
the hypertensive range in at least 4 of 6 consecu- shift is not significant enough to cause BP reduc-
tive dialysis treatments should prompt a more tions. This is because these patients tend to have
extensive evaluation of BP and volume manage- lower pre-dialysis serum levels of osmotically
ment, including home and/or ABPM [10]. active solutes such as creatinine, blood urea
Intradialytic hypertension occurs in 5–15% of nitrogen, phosphate, albumin and a lower inter-
HD patients [11] and is associated with poor dialytic weight gain relative to other HD patients
short- and long-term cardiovascular outcomes [12]. The dialysate-to-plasma sodium gradient is
[12–14]. Patients prone to developing intradia- also an important contributor to intradialytic
lytic hypertension are characterized by non- osmolar shifts and intradialytic hypertension in
modifiable factors such as increased age, male predisposed patients. A higher dialysate-to-
gender, and Caucasian race [15]. In addition, plasma sodium gradient results in less effective
modality-related factors such as short dialysis extracellular fluid (ECF) removal as a higher gra-
duration, short dialysis vintage, and smaller dient favors both ECF and intracellular fluid
interdialytic weight gain and hence low ultrafil- removal rather than ECF removal alone [16, 17].
tration volumes per treatment have also been The absence of active therapeutic intradialysis
noted to typify HD patients who develop recur- BP control with antihypertensives occurring
rent intradialytic hypertension [15]. These either as a result of withholding all BP lowering
patients’ metabolic profile is characterized by agents prior dialysis sessions, or their loss into
lower Hb, creatinine, albumin, calcium and phos- the dialysate during dialysis sessions has addi-
phate levels, and a lower total iron binding capac- tionally been identified as a contributing factor to
ity [15]. the occurrence of recurrent intradialytic hyper-
The pathophysiologic mechanisms underlying tension [18].
intradialytic hypertension have not been fully Intradialysis BP levels may become severely
elucidated, but a few associations have been elevated necessitating the use of immediate
release or short acting BP lowering agents to SCA represents an interplay between a trigger-
lower the BP. The long-term management of ing event for a fatal arrhythmia and a predispos-
intradialytic hypertension involves a downward ing/underlying CV disease. CKD and kidney
review of dry weight over time i.e. dry-weight failure are associated with myocardial structural
probing, reducing dialysate sodium to reduce the changes, such as left ventricular hypertrophy
dialysate-plasma gradient, and the use of (LVH), coronary vascular calcification, and myo-
antihypertensives prior to commencing dialysis cardial fibrosis, which in turn disrupt the architec-
sessions. Dry weight probing addresses the ture of cardiac electrical pathways resulting in
chronic ECW excess state in these patients while arrhythmogenic zones and conduction delays in
a less steep or flat dialysate-plasma sodium gra- fibrotic areas [25]. Fluxes in electrolyte levels
dient ensures that ultrafiltration effectively especially with regards to dialysate potassium and
addresses the ECV compartment alone. calcium (low levels of both predispose to pro-
Withholding antihypertensives prior to dialysis longed QT interval and QT dispersion on ECG),
sessions should not be a broad approach applied intracorporeal fluid compartment volume fluctua-
to all dialysis patients. In patients with recurrent tions, and myocardial stunning, constitute identi-
intradialytic hypertension, non-dialyzable anti- fied triggers [26, 27]. A relationship exists
hypertensives (e.g. Amlodipine) can be adminis- between dialysis timing and the occurrence of
tered [19]. While the choice of antihypertensives SCD. HD patients are most at risk after a long
is driven by factors such as comorbid states and interdialytic interval (>2 days), with the risk being
underlying CV risk factors, ACEis/ARBs and highest in the last 12 h of the interdialytic period,
β-blockers are particularly beneficial. during or after the first dialysis session of the
week and within 6 h after a dialysis session [28–
31]. Both tachy- and bradyarrhythmias are known
ardiac Arrhythmias, Sudden Cardiac
C to occur in the dialysis population. While tachyar-
Arrest, and Sudden Cardiac Death rhythmias have been widely held to be the com-
moner cause of SCA, more recent data suggests
Cardiovascular disease remains an important cause that bradyarrhythmias account more for fatal
of mortality in kidney failure patients with sudden intradialysis arrests. Tachyarrhythmias include
cardiac death (SCD) accounting for 78% of CV atrial fibrillation, supraventricular tachycardia,
causes of death [20]. SCD has been defined as “an and non-sustained ventricular tachycardia [32].
unexpected death due to cardiac causes in a person Management strategies are directed towards
with known or unknown cardiac disease, within 1 h the prevention of arrhythmias and encompass
of symptom onset (witnessed SCD) or within 24 h avoiding rapid electrolyte shifts during dialysis
of the last proof of life (unwitnessed SCD) [20, sessions, more frequent dialysis session schedul-
21]”. Included in this definition is a distinct sub- ing to avoid long interdialytic intervals, the use of
group of patients in whom sudden cardiac arrest cardioprotective agents such as ACEi/ARB which
(SCA) in dialysis is the cause of SCD. The risk for are known to have a beneficial effect on modify-
arrhythmias and SCA is higher among HD patients ing myocardial hypertrophy and fibrosis, and
relative to CAPD patients in the first 2 years of β-blockers with pleiotropic benefits beyond BP
dialysis initiation but this risk equalizes thereafter control including inhibitory effect on the sympa-
[16]. Forty percent of deaths among dialysis thetic system, promoting of heart rate variability,
patients are attributable to arrhythmias and SCA and improving baroreceptor sensitivity. The use
with the reported event rates of occurrence ranging of cardiac devices such as implantable defibrilla-
between 4.5–7.0 per 100,000 HD sessions [22–24]. tors has also been advocated. Other causes of
Prognosis following intradialysis SCA is dismal SCD in dialysis patients other than fatal arrhyth-
with 7.8% dying intradialysis following unsuccess- mias identified from autopsy series include acute
ful resuscitative attempts while only 40% remain myocardial infarction and dissecting aortic aneu-
alive 2 days post event [23]. rysms [33].
Dialysis Pericarditis or complete pericardiectomy—may be necessary

in dialysis pericarditis with recurrent pericardial
Dialysis pericarditis refers to pericarditis occur- effusions [38].
ring 8 weeks after the initiation of dialysis [34].
The exact incidence and prevalence of dialysis
pericarditis is unknown as most data usually do ialysis Access Ischemia Steal
D
not make the distinction between uremic and Syndrome
dialysis pericarditis. While uremic and dialysis-
related pericarditis share a similar etiologic fac- Dialysis access ischemic steal syndrome (DAISS)
tor of the accumulation of uremic toxins, is an access-related complication seen in 1–8%
dialysis-related pericarditis is perpetuated by of HD patients with arteriovenous (AV) dialysis
inefficient solute clearance during dialysis (not accesses [41]. While most AV access demon-
achieving kt/V), infrequent scheduling, and sub- strates evidence of distal arterial steal, not all
optimal dialysis flow rates [34, 35]. It must be patients will develop the ischemic symptoms that
borne in mind that pericarditis from other etiolo- typify this complication. It occurs as a result of
gies such as Dressler’s syndrome, connective tis- decreased distal arterial blood flow beyond the
sue disorders like systemic lupus erythematosus, point of an AV anastomosis; blood diversion
infections or malignancies can also account for through the anastomosis accounts for the distal
pericarditis in the dialysis patient. For diagnostic “steal” of blood supply while resultant distal
purposes, atypical electrocardiographic (ECG) hypoperfusion and ischemia rather than the steal
findings are more commonly observed [36]. An alone accounts for symptoms. Risk factors for
associated infection should be suspected in the DAISS include a proximally placed AV access
patient with dialysis pericarditis who has the rep- i.e. brachial artery access points, diabetes melli-
resentative ECG tracings of widespread ST ele- tus, peripheral vascular disease, age > 60 years,
vation or PR segment depression seen in and female gender [41]. Clinical manifestations
pericarditis unrelated to kidney failure. include cold hands, pain in the hands during dial-
Inflammatory markers and white cell counts are ysis (could also occur off dialysis), tingling and
also elevated [37, 38]. numbness in the hands, sensory and motor defi-
The characteristic chest pain of pericarditis is cits, and skin changes such as ischemic fingertip
infrequently observed in these patients. More fre- ulcers and dry gangrene of the digits in chronic
quently, intradialysis hypotension and clinical cases [42]. In addition to typical history and
features of heart failure from complicating peri- examination findings, a doppler ultrasonography
cardial effusion are the clinical manifestations in to assess access flow and establish improved dig-
this patient group [34–36]. Non-specific constitu- ital pressures with compression at the AV anasto-
tional symptoms of malaise, chills and fever, motic site strongly suggest the presence of
cough, and dyspnea have also been observed. significant steal [42]. An arteriography is critical
Treatment approaches involve improving solute to making a diagnosis of steal and associated dis-
clearance by augmenting dialysis parameters— tal hypoperfusion and helps to guide the best
improving blood flow, increasing dialysis dura- treatment approach. The available treatment
tion, and/or increasing frequency. Trial data [39, modalities are varied depending on the severity
40] demonstrates no benefit of non-steroidal anti- of symptoms and the pathophysiologic vascular
inflammatory drug (NSAID) use while data is hemodynamic processes at play and range from
poor for the efficacy of steroids or colchicine. observation of symptoms to ligation of the AV
Surgical treatment—needle pericardiocentesis, access in extreme situations [42, 43].
pericardiotomy with continuous drainage, partial
Practice Point 1: Cardiovascular Complications of Haemodialysis
Complication Causes Management

Intradialytic See Fig. 18.1 Acutely:
hypotension – rendelenburg, stop ultrafiltration, fluid
bolus.
– Consider underlying cause (see
Fig. 18.1)
– Dietary sodium restriction
– Bicarbonate buffer
– Review patient’s dry weight
– Adjust dialysate temperature to 36.5
– Avoid meals during dialysis, adjust
timing of anti-hypertensives.
– Consider midodrine or L-carnitine
supplementation
Intradialytic – Chronically expanded – Review dry weight
hypertension extracellular volume – Consider reduction in dialysate
– Lower pre-dialysis levels of sodium
osmotically active solutes – Review and optimise medications
– Lower intra-dialytic weight – Consider use of non-dialyzable
gain antihypertensives, e.g. amlodipine.
– Inadequate BP control prior to
dialysis
– Loss of anti-hypertensives into
dialysate
Cardiac arrhythmias Both tachy- and bradyarrhythmias Prevention is key
– Underlying cardiovascular – Avoidance of rapid electrolyte shifts
disease with resultant myocardial – Avoiding long interdialytic intervals
structural abnormalities – Use and up-titration of
– Fluxes in electrolyte levels cardioprotective drugs
– Intracorporeal fluid
compartment volume fluctuations
Dialysis pericarditis Overlap between uraemic/dialysis- – Improvement of solute clearance
related pericarditis – Augmentation of dialysis parameters
– inefficient solute clearance – Consider steroids, colchicine (though
– suboptimal dialysis flow rates a paucity of evidence)
Consider other aetiologies for
instance connective tissue disease
Dialysis ischaemia Risk factors include: Severe ischaemia warrants invasive
steal syndrome – Proximally placed AV access treatment. Options depend on individual
(DAISS) – Diabetes, peripheral vascular anatomy and pathology but include:
disease, age >60 years, – Angioplasty to inflow arterial stenosis
females. – Precision banding
– Ligation
Neurological Complications reported in 7–50% of children with kidney failure

of Haemodialysis [44, 45]. Young age, a medical history of sei-
zures, dyselectrolytemias such as hypocalcemia
Seizures and hypomagnesemia, as well as metabolic fac-
tors (e.g. hypoglycemia) and sustained acid-base
Hemodialysis-related seizure (HRS) is a com- abnormalities are known risk factors (Fig. 18.3).
mon complication frequently observed in the Rapid clearance of anti-convulsant drugs during
younger age dialysis population. It has been dialysis (in patients known with epilepsy), or use
Dialysis disequilibrium
syndrome
Drugs: Toxins:
– lntradialytic removal of anticonvulsants – Alcohol withdrawal
– Use o– epileptogenic drugs – Aluminum intoxication
HD-associated
seizures
Focal neurological disease: Others:
– lntracerebral / intracranial hemorrhage – Sustained hypotensive episodes
– Microangiopathy – Uremic encephalopathy
– Atheroembolism – Hypertensive encephalopathy
Electrolyte / Metabolic:
– Hypocalcaemia
– Hypomagnesemia
– Hypoglycaemia
Fig. 18.3 Factors implicated in haemodialysis-associated seizures
of epileptogenic drugs (e.g. theophylline) can be as a result of HD, with no particular pathogno-
triggers of a seizure disorder during dialysis. In monic characteristics, and which spontaneously
addition, HD-related processes such as a rela- resolves within 72 h of the termination of the
tively rapid clearance of solutes such as urea can dialysis session [47]. Diagnostic criteria help to
lead to an osmotic gradient between the brain and distinguish DRH from other headache phenom-
the plasma, leading to dialysis disequilibrium ena that may be observed in HD patients [47]:
syndrome (DDS): brain edema that manifests as
neurological symptoms such as headache, nau- Diagnostic criteria for dialysis-related headaches
sea, vomiting, muscle cramps, tremors, disturbed (DRH) [47]
consciousness, and convulsions. Other 1. Patient is on HD
HD-related processes including the use of acetate 2. Two of the following to demonstrate HD
causality:
buffer, heparinization-related intracerebral hem- (a) Headache occurring during an HD session
orrhage, and erythropoietin administration have (b) Each headache episode worsening during the
also been associated with HRS [45, 46]. dialysis session and/or each headache episode
resolving within 72 hours of HD completion,
Generalized tonic-clonic seizures are more com-
3. Three headache episodes meeting the specifics
monly observed than non-convulsive seizures above
[45]. There is a dearth of clinical trial efficacy 4. Headaches no longer occurring after renal
data regarding the efficacy of antiepileptic drugs transplantation and cessation of HD altogether
in the prevention and management of HRS.
Diazepam, a benzodiazepine that is non- A previous diagnosis of primary headache
dialyzable has been reported to prevent the recur- appears to be a risk factor for
rence of HRS [44]. DRH. Pathophysiologic mechanisms have been
attributed to changes in levels of solutes such as
sodium, magnesium, and urea as well as intradia-
Headache lytic changes in blood pressure and volume status
[48, 49]. No clinical trial data is available to
Dialysis-related headache (DRH) is a common guide prophylactic and therapeutic approaches to
neurologic complication of HD and is described DRH management. There are case reports [50,
by the International Headache society as a sec- 51] describing the prophylactic role of chlor-
ondary form of headache occurring during, and promazine, ACE-i [51], magnesium oxide and
AL GRAWANY
nortriptyline, while paracetamol and the ergot towards the end of a dialysis session and may
alkaloids (ergotamine, dihydroergotamine) have result in the premature termination of a session
also been shown to have therapeutic benefits of dialysis. Cramps have been reported in up to
[50]. The risk of AV fistula closure with alkaloid 86% of HD patients [55]. Short-term painful
derivatives necessitates caution in its application discomfort to the patient and long-term inade-
for the treatment of DRH. quacy of dialysis sessions are consequences of
muscle cramps that should be avoided. Muscle
cramps usually occur in the lower extremities
Dialysis Dementia but can also manifest in the arm, hand, and
abdominal muscles. The exact causes of cramps
Dialysis dementia is prevalent in about 4% of the during dialysis are unknown but the temporal
HD population [52], and is associated with an occurrence towards the end of a treatment ses-
increased risk of dialysis withdrawal and death. sion lend credence to the role of changes in
With the highly restricted use of aluminum- ECV and solute/osmolarity shifts in promoting
containing phosphate binders and improved water the abnormal muscular energy utilization and
treatment systems that safeguard against aluminum cramp triggering. Muscle cramps are observed
contamination of dialysates, dialysis dementia in in up to 74% of intradialytic hypotensive epi-
HD patients is now rarely observed [53]. It is a sub- sodes [56]. It is believed that volume contrac-
acute, progressive, and fatal dementia occurring due tion from high ultrafiltration rates account for
to aluminum deposition in the cerebral cortex. More this. Preventive and treatment approaches thus
recently, risk factors for dialysis-related dementia involve limiting interdialytic weight gain
include the poor clearance of middle-molecules (which limits dialysis sessions UF goals) and
with neurotoxin activity; the preservation of resid- sequential/controlled ultrafiltration, respec-
ual renal function in HD patients which ensures to tively. Hyponatremia has also been implicated
an extent the excretion of middle molecules has as a predisposing factor to muscle cramping by
been associated with reduced odds of dialysis its role in influencing serum osmolarity and
dementia [52]. The chronic oxidative stress and influencing water shifts across the various
inflammatory states induced by HD have also been human volume compartments. Magnesium
implicated. Risk factors for dementia in the general plays a critical role in skeletal metabolism
population (increased age, race, low educational influencing neuromuscular excitability. It also
status, comorbidities such as cerebrovascular dis- plays a regulatory role in sodium, potassium,
ease and diabetes) are also observed in patients with and calcium ion channels transport.
dialysis dementia. The management of aluminum- Hypomagnesemia among HD patients contrib-
related dementia includes aluminum chelation with utes to the occurrence of dialysis-related
deferoxamine, improved water treatment methods, cramps. Magnesium is freely diffusible across
and substituting aluminum-containing phosphate the dialysis membrane and increasing dialysate
binders with non-aluminum alternatives (calcium- magnesium concentrations cause an increase in
or non-calcium-based binders) [54]. The clinical serum magnesium thus promoting neuromuscu-
efficacy of medications for dementia in the general lar excitability stability. The use of magnesium-
population have not been defined in the dialysis based phosphate binders can also be employed
population, but hold promise. to improve serum magnesium levels in the HD
population [57]. Broad non-specific treatment
approaches employed include carnitine, and
Dialysis-Related Muscle Cramps vitamins C and E supplementation [58, 59]. The
use of benzodiazepines has also been docu-
Muscle cramps are a frequent muscular compli- mented [60].
cation in HD and typically present, usually
Practice Point 2: Neurological Complications of Haemodialysis

Seizures See Fig. 18.2 Acutely:
– stop dialysis, check glucose and bloods,
rule out hypoglycaemia, manage as per
local emergency protocols.
Identify and treat underlying causes.
Consider antiepileptics in conjunction with a
neurologist—no specific evidence to guide
choice of agent.
Dialysis related Proposed mechanisms include: – Rule out other potential causes of
headache – changes in solute levels headache
– intradialytic blood pressure – Analgesia
and volume changes No specific clinical trial data to support
prophylactic or therapeutic measures.
Dialysis Dementia – Chronic oxidative stress and – Investigate and treat as per non-CKD
inflammatory state associated patients.
with haemodialysis – Chelators for treatment of aluminium
– Metabolic and uremic factors toxicity
– Underlying cardiovascular
risk factors
– Aluminium intoxication (now
rarely seen)
Dialysis related – Changes in extracellular Focussed on prevention:
muscle cramps volume – Avoid excessive interdialytic weight gain
– Solute/osmolarity shifts. – Avoid eating during haemodialysis
– Hypomagnesemia – Consider increasing dialysate magnesium
concentration and/or use of magnesium
containing phosphate binders
Stretching/warm compresses may help relieve
symptoms
Haematologic Complications formaldehyde, chlorine are common causes of

of Haemodialysis intradialytic haemolysis [62, 63]. Metals
including Copper, zinc and aluminium and
Intra-Dialytic Haemolysis nitrates have also been implicated [64].
Overheated dialysate (usually above 47 °C). If
This is an uncommon but important complica- the patient’s osmolality falls below 250 mOsm/
tion of HD because of the significant risk of kg, either because of error in mixing dialysate
morbidity and mortality [61]. Fig. 18.4 summa- (hypo-osmolar dialysate) or use of plasma
rizes the possible aetiology of intradialytic hae- expanders, intravascular haemolysis may occur
molysis. Factors that increase mechanical or [65, 66]. A host of patient factors predispose to
shear stress on the red blood cells include intravascular haemolysis—malignant hyperten-
defective blood lines causing kinking in the sion, autoimmune conditions like Systemic
lines, dialysis techniques that increase turbu- lupus erythematosus and thrombotic thrombo-
lence of flow like using a single needle tech- cytopenic purpura, sickle cell anaemia, G6PD
nique, and when relatively high blood flow deficiency and hypersplenism. Medications that
rates occur in the presence of small cannula may induce haemolysis in dialysis patients
size [10]. Contaminants, including chemicals include aspirin, sulphonamides, nitrofurantoin,
used for water disinfection like chloramine, quinidine and hydralazine [61, 67].
MEDICATIONS:
• Aspirin
• Sulphonamides
• Nitrofurantoin
• Quinidine
• Hydralazine
EXTRACORPOREAL: DIALYSATE:
• Mechanical or shear stress, INTRADIALYTIC Contaminants / chemicals used for disinfection

• Single needle technique, (chloramine, formaldehyde, chlorine);
• Kinked blood lines, HAEMOLYSIS Metals (Copper, zinc and aluminium);
• High blood now/small cannula size, Nitrates;
• Rough cut surface dialysis membrane Osmolality (< 250 mOsm/Kg)
PATIENT:
• Malignant hypertension,
• autoimmune conditions (e.g., SLE and TTP),
• sickle cell anaemia,
• G6PD deficiency
• hypersplenism
Fig. 18.4 Proposed aetiological factors for the devel- SLE Systemic lupus erythematosus, TTP Thrombotic
opment of intradialytic haemolysis thrombocytopenic purpura, G6PD Glucose-6-
phosphate dehydrogenase
The symptoms are non-specific. Chronic and ensuring correct positioning of tubings in the
intradialysis haemolysis is usually asymptom- dialysis machine pumps.
atic, presenting as chronic anaemia with fatigue
or erythropoietin resistance. Acute intradialysis
haemolysis presents with nausea, vomiting, Haemorrhage
abdominal pain, diarrhoea, increasing dyspnoea
and hypertension, headache, dark urine and pos- The need for extracorporeal anticoagulation dur-
sibly death. Inspection of the extracorporeal cir- ing HD has introduced an increased likelihood
cuit may reveal a cherry red (less opaque) colour for bleeding complications especially for indi-
which may be associated with a pink tinged dial- viduals who are at increased risk. Major bleed-
ysate fluid if haemolysis is massive. Another ing episodes occur in 1.7% to 3.7% of HD
indicator is a reduction in both arterial and venous patients [69]. Bleeding can occur at any site—
circuits suggesting a kink in the bloodline. vascular access site [70], gastrointestinal, gall
Important investigations include haptoglobin, bladder, intracerebral, subdural, retroperito-
LDH, Coomb’s test, blood film, serum free hae- neum, perinephric or even into the vitreous
moglobin and methaemalbumin. humor. Factors that increase risk of intradialysis
Once acute haemolysis has been identified, it haemorrhage include suboptimal control of BP,
is important to stop dialysis immediately and not pre-existing gastrointestinal lesions, renal cystic
to return the blood in the extracorporeal circula- disease, diabetic retinopathy, recent surgery or
tion to prevent fatal arrythmias from hyperkalae- trauma, concomitant use of warfarin or aspirin
mia. Some patients may require ICU care. Serum and acute stroke [71]. The clinical presentation
potassium levels should be monitored closely. usually depends on the site of bleeding.
Blood products should be given as indicated. The Prevention or minimization of bleeding may be
aetiology of the haemolysis should be investi- done by using dialysis modes that do not require
gated immediately and identified to prevent use of systemic anticoagulation including using
repeat episodes [68]. Prevention of this compli- CAPD, heparin-free HD, regional anticoagula-
cation requires strict adherence to protocols for tion with citrate, prostacyclin or mesilates.
dialysis water safety by appropriately trained Regional heparin anticoagulation may also be
staff; avoidance of small needle/large flow rates employed.
Thrombocytopaenia and Other Hemodialysis associated heparin-induced

Platelet Function Abnormalities thrombocytopaenia (HIT) has two types. Type I
HIT occurs within 48 h of exposure to heparin, is
Reduced platelet count is known to be a feature non-immune and caused by heparin’s direct
of CKD in both pre-dialysis CKD patients and effect on platelet activation. The platelet count
those on maintenance HD. This is less pro- returns to normal with continued heparin use.
nounced for kidney failure patients on CAPD. For Type II HIT occurs in about 0.2% of individuals
maintenance HD patients, thrombocytopaenia exposed to heparin [75]. It is potentially life
may occur from the effect of the dialyzer mem- threatening because of its prothrombotic effect. It
brane on platelets or from an idiosyncratic reac- has an autoimmune basis—antibodies to the hep-
tions to heparin anticoagulation (heparin-induced arin-PF4 complex. HIT II is usually diagnosed
thrombocytopaenia) [72]. In most cases, throm- 5–14 days after heparin administration; platelet
bocytopaenia from dialyzer membrane is sub- count reduces by at least 50% of pre-heparin
clinical. Platelet count is known to decrease in administration level and the patient has throm-
the first 1–2 h intradialysis, then returns to pre- botic (not bleeding) sequelae [75]. Immunoassays
dialysis levels [72]. The degree of HD-associated to identify antibodies to heparin-PF4 complex is
thrombocytopaenia is dependent on the type of useful for making a definitive diagnosis. The
membrane and sterilization technique [73, 74]. mainstay of therapy is to discontinue heparin and
Polysulfone membranes sterilized by electron all heparin-related products. Use direct thrombin
beam appear to be most common culprit. Platelet inhibitors like lepirudin or indirect factor Xa
factor-4 (PF4), β-thromboglobulin, LDH, CD62P inhibitors like fondaparinux or danaparoid.
and CD63 which measure platelet activation have Others have used intravenous immunoglobulin
been shown to be elevated during HD. for treatment.
Practice Point 3: Haematological Complications of Haemodialysis

Intra-dialytic See Fig. 18.3 If acute haemolysis:
haemolysis – Stop dialysis immediately without
returning blood in extracorporeal
circulation
– Monitor serum potassium closely
– Liaise with haematology
– Patient may require critical care
support
Haemorrhage – Suboptimal BP control Consider measures to prevent or
– Underlying disease at risk of minimise bleeding risk
bleeding, e.g. gastrointestinal – Heparin-free HD
lesions, renal cystic disease, diabetic – Regional anticoagulation with
retinopathy citrate, prostacyclin or mesilates
– Recent surgery or trauma
– Concomitant use of warfarin or
aspirin
Thrombocytopenia/ – Platelet interaction with the dialyser – Most cases of thrombocytopenia
Platelet function membrane are subclinical and transient.
abnormalities – Heparin-induced thrombocytopenia If HIT suspected:
– use clinical prediction tool i.e. the
4Ts score +/− send HIT antigen
assay.
– Treatment involves:
• Discontinuation of heparin
• Non-heparin based
anticoagulation e.g. argatroban.
Other Complications 1.2–2.9 per 100 patient-years [82]. HCV and

of Haemodialysis HBV infections are associated with longer dialy-
sis duration and frequency of blood transfusion
Dialysis-Associated Pruritus [83]. Other factors include dialyzer reuse, inter-
nal contamination of HD monitors and more
The prevalence of pruritus among adult HD importantly, failure of dialysis staff to adhere to
patients has been estimated to be between strict protocols as regards use of multi-dose med-
49–61% [76]. The aetiology and pathophysiol- ications. Hepatitis C virus (HCV) and HIV
ogy is unclear. Dialysis inadequacy, hyperpara- appear to be less infectious than HBV in HD
thyroidism, hypercalcemia and hypermagnesemia units. Outbreaks of these blood-borne viruses can
have been associated with dialysis-associated be avoided by strict adherence to infection con-
pruritus [77]. It may also be associated with dry trol protocols in HD units.
skin or occur without it. Treatment include both The incidence of catheter-related bloodstream
topical and systemic agents. Moisturizers, mild infection (CRBSI) is 2.5–6.6 per 1000 catheter-
topical steroids, 0.025% capsaicin cream, topical days with rates much higher in non-cuffed cath-
tacrolimus, parathyroidectomy, oral antihista- eters than cuffed and tunnelled catheters. Most
mines, pregabalin, gabapentin, naltrexone have HD catheters are colonized within 24 h of place-
all been used with varying results [77]. A more ment [84]. Inoculation of bacteria is from the sur-
recent medication is nalfurafine [78], which in rounding skin or the hands of healthcare works
combination with skin care, has been found to be during manipulation. Bacterial biofilm which
effective. may occur within the lumen or externally is asso-
ciated with persistent and metastatic infections.
A delay in antibiotic treatment may increase the
Post-Dialysis Fatigue risk of metastatic infection which may lead to
osteomyelitis, infective endocarditis, septic
This is a common complication of HD occurring arthritis, spinal and psoas abscess [84]. Risk fac-
in as much as 50% of adult HD patients. It is tors for CRBSI include location of insertion site
associated with high levels of tumour necrosis (femoral catheters more likely to be infected than
factor, rapid changes in BP during dialysis, high subclavian and jugular catheters); summer
ultrafiltration levels, osmotic disequilibrium and months have higher incidence of CRBSI inci-
psychologic factors like depression [79, 80]. It dents and the elderly may have lower incidence.
may be commoner in old age and those with heart New innovations like antimicrobial coated cath-
disease. Treatment usually involves increasing eters, protective barriers, prophylactic intralumi-
the frequency of HD, use of low intensity exer- nal antimicrobial lock therapy and use of
cises, treatment of depression, adjustment of needleless connector devices [84]. The com-
dialysis prescription and adequate treatment of monly cultured organisms in CRBSI include
malnutrition, anaemia and heart failure. coagulase negative Staphylococcus species,
Staphylococcus aureus and enterococcus species.
Candida species infections also occur. Empirical
Infections in Hemodialysis Patients treatment with vancomycin, a cephalosporin or
carbapenem is usually appropriate. In many
The common infections encountered as compli- cases, removal of the catheter is necessary.
cations in HD include catheter-related blood
stream infection (CRBSI), HIV and hepatitis B
and C infection. Nosocomial transmission of Priapism
hepatitis B and C still occurs in HD units despite
significant reduction over the decades [81], the This a rare complication of HD occurring 2–7 h
incidence of nosocomial HCV infection is about after a treatment session and associated with
erythropoietin or androgen therapy [85]. Dialysis ATPase in the cochlea has also been implicated
induced hypoxaemia and acidosis have also been as a pathophysiologic pathway for sensorineural
suggested as risk factors. Priapism may resolve hearing loss in HD patients [86]. Some have sug-
spontaneously or require the use of surgical gested osmotic disequilibrium in the inner ear
intervention. initiated or worsened by HD. Patients on HD will
benefit from pure tone audiometry for monitoring
of hearing function [87].
Hearing Loss Acute visual loss following HD is an uncom-
mon complication which could be caused by sud-
Hearing impairment affecting low, middle and den hypotension or rapid ultrafiltration leading to
high frequency sounds is not uncommon among a non-arteritic anterior ischaemic optic neuropa-
adult HD patients. The stria vascularis and renal thy [88]. The risk factors for visual loss caused
tubular cells have similar modes of active trans- by HD include diabetes mellitus, dyslipidaemia,
port of fluids and electrolytes and may be respon- smoking and hypertension. Immediate post-
sible for the simultaneous affectations in dialysis reduction in ocular perfusion pressure,
medications that have ototoxic and nephrotoxic choroidal and retinal thickness has been reported
properties [86]. An inhibition of the Na+-K+ [89].
Practice Point 4: Other Complications of Haemodialysis

Acute visual • Causes include sudden hypotension or rapid
loss ultrafiltration leading to a ischaemic optic
neuropathy
• Immediate post-dialysis reduction in ocular
perfusion pressure, choroidal and retinal
thickness has been reported
Hearing loss • Cochlear stria vascularis and renal tubular cells
have similar modes of active transport of fluids
and electrolytes
• Suggested mechanisms include HD-induced:
• Osmotic disequilibrium in the inner ear
• Inhibition of the the Na+-K+ ATPase in the
cochlea
• Inadequate BP control prior to dialysis
• Loss of anti-hypertensives into dialysate
Priapism • Rare complication, associated with • May resolve spontaneously
erythropoietin or androgen therapy. • Surgical intervention
• Dialysis induced hypoxaemia and acidosis
suggested as risk factors.
Post-dialysis Associated with: • Increased frequency of HD
fatigue • Rapid changes in BP during dialysis • Adjust dialysis prescription
• High ultrafiltration levels • Treat depression
• Osmotic disequilibrium • Optimise nutrition and
Concomitant depression treatment of co-morbidities
such as anaemia and heart
failure
Dialysis- Multifactorial—following all implicated • Topical—Moisturisers, mild
associated • Dialysis inadequacy topical steroids, topical
pruritus • Hyperparathyroidism tacrolimus,
• Hypercalcaemia • Oral—antihistamines,
• Hypermagnesaemia pregabalin, nalfurafine.
Conclusions normal except for a platelet count of 81,200/

mm3. His platelet count was 223,400 two
Returning to our patient: He has been a dialysis months ago. She had no splenomegaly and no
patient for several years. His blood pressure at abnormal bleeding. What is the best manage-
the start of haemodialysis was 130/80 mmHg, ment option for this patient?
which was usual for him after taking his antihy- A. Blood culture and commence empirical
pertensive medications each morning. He was IV antibiotics
afebrile, and had been otherwise well. He noted B. Use low molecular weight heparin for
that he had been passing less urine recently, and treatment of DVT and continue hemodi-
that his interdialytic weight gains have over the alysis using standard protocol
last few weeks increased to around 4 kg, and he C. Use dabigatran for treatment of DVT and
freely admits to having difficulty with fluid and continue hemodialysis using standard
salt restriction. At the point of review, he had protocol
completed 3 h of haemodialysis with an ultrafil- D. Use warfarin for the treatment of DVT,
tration of 3.5 L. You advise his nurse to adminis- discontinue all heparin products and use
ter a 250 mL bolus of 0.9% sodium chloride, argatroban for hemodialysis.
following which his blood pressure improves to E. Give platelet concentrate infusion, IV
110/80 mmHg, and he is able to successfully antibiotics, low molecular weight heparin
complete 4 h of dialysis without further and continue hemodialysis using standard
ultrafiltration. protocol.
The likely cause of his intradialytic hypoten- The correct answer is D.
sion is multifactorial: whilst fluid restriction can This patient has developed heparin-
be difficult, particularly for those new to dialysis, induced thrombocytopenia (HIT).
it is also an issue where patients with a significant Paradoxically, they present with thrombotic
native urine output become oligo-anuric on hae- phenomena instead of bleeding tendencies.
modialysis. Having excluded other contributory Differential diagnoses include drug-induced
acutely reversible causes, in addition to better thrombocytopenia from use of quinine, quini-
adherence to fluid restriction to limit interdialytic dine, chloroquine and sulfonamides; bacterial
weight gains, the patient may be advised to sepsis; TTP, ITP, disseminated intravascular
reduce or omit their antihypertensive medication coagulopathy and splenomegaly. We do not
on dialysis days in order to facilitate ultrafiltra- have any information regarding medication
tion to euvolaemia. use except heparin. CBC would have shown
neutrophilia if there is bacterial sepsis. The
patient had no splenomegaly. Use of any hep-
Questions arin preparation will worsen the condition.
Platelet concentrate is known to worsen
thrombosis. Argatroban, bivalirudin,
1. A 43-year-old female who has been on main- fondaparinux are non-heparin anticoagulants
tenance hemodialysis for 11 months presented used in HIT.
with unilateral leg swelling and was noticed 2. Which of the following is not useful for the
to have fever, chills, flushing, worsening treatment of dialysis-associated pruritus?
breathlessness and chest pain following a A. Naltrexone
bolus of IV Unfractionated heparin injection. B. Skin moisturizers and low potency topical
A doppler ultrasound scan of the limb was steroids
suggestive of a deep venous thrombosis. At C. Nalfurafine
presentation for the next hemodialysis ses- D. Propoxyphene
sion, she was noticed to have gangrene of E. Gabapentin
three toes in her left lower limb. CBC was The correct answer is D.
Propoxyphene is a narcotic pain reliever reducing hemoglobin levels. However, the lat-
which is not known to have any effect on pru- ter will affect multiple dialysis patients in the
ritus. All others have been shown to have ben- same centre. Gram positive organisms like
eficial effect in individuals with pruritus. Staph Aureus are the commonest organisms
3. A 56-year-old woman with end-stage renal implicated and having an established fungal
disease secondary to diabetic nephropathy catheter-related infection is an indication for
uses a cuffed, tunneled, right internal jugular removing the catheter.
catheter as vascular access for hemodialysis 4. A 60-year-old diabetic female with a current
for 5 months. After the first 35 minutes of HD, weight of 102 kg has recently commenced
she develops nausea and rigors and has a tem- hemodialysis. Dry weight estimation by bio-
perature of 38.3 °C. Her BP drops from electrical impedance analysis is 93 kg. She
157/80 to 100/61 mmHg, and her heart rate is has been unable to complete her last 3 sched-
113 beats per minute, regular. She had a simi- uled HD sessions due to intra-dialysis MAP
lar experience during dialysis 3 days ago, but drops up to 15 mmHg. The following are car-
the temperature was 37.7 °C and she had tran- diovascular and neuroendocrine mechanisms
sient rigors. Examination revealed mild ery- that are expected to have occurred in this
thema and tenderness of the exit site but no patient except
purulent discharge. No other patient having A. Augmented myocardial contractility
dialysis at the centre has similar occurrence. B. Increased peripheral resistance
What is the most correct statement? C. Activation of the parasympathetic nervous
A. Take a swab from the exit site and start system
empiric antibiotic D. Activation of the Renin-Angiotensin-
B. The most likely cause of this intradialysis Aldosterone system
complication is bacterial contamination of E. Increased heart rate
dialysis water The correct answer: C.
C. Commence IV antibiotic following local Options A, B, D and E are all known com-
resistance pattern for Gram positive and pensatory, adaptive mechanisms that occur
negative bacteria after taking samples during hemodialysis to prevent blood pressure
from the exit site, one from the catheter drops intradialysis.
lumen (hub), and one from the bloodline. 5. One of the following can prevent the occur-
D. The most common causative organisms rence of intradialytic hypertension
are Gram negative organisms A. A steep dialysate-to-plasma sodium gradi-
E. Catheter removal is not essential if a fun- ent favoring intracellular fluid shifts alone
gal organism is cultured. B. A moderate dialysate-to-plasma sodium
The correct answer is C. gradient favoring net extracellular fluid
This is most likely a catheter-related blood shifts
stream infection. C. A moderate dialysate-to-plasma calcium
The identification of the offending organ- gradient favoring total body water fluid
ism and sensitivity pattern is critical in the loss
establishment of correct treatment and pre- D. A steep dialysate-to-plasma sodium gradi-
vention of metastatic infection and death. ent favoring total body water fluid loss
Taking a swab sample from the exit site only E. A zero dialysate-to-plasma sodium gradi-
may not establish the offending organism(s) ent to prevent rebound hypervolemia
as catheter and bloodline samples are also Correct answer: B.
important. Bacterial contamination of water As sodium plays a central role in determin-
would present with chills/rigors within one ing serum osmolarity and thus intravascular
hour of treatment associated with fever one to volume, sodium shifts induced by dialysate-
two hours after treatment, hypotension and serum sodium gradients induce fluid
ovement across the various fluid compart-

m roids and NSAIDs have not been consistently
ments, principally the intracellular and shown to be helpful.
plasma/extracellular fluid compartments. It 7. A 56-year-old woman with end-stage renal
has been demonstrated by bioimpedance tech- disease secondary to diabetic nephropathy
niques that steeper sodium gradients of the uses a cuffed, tunneled, right internal jugular
dialysate relative to serum promotes intracel- catheter as vascular access for hemodialysis
lular fluid loss rather than plasma/extracellu- for 5 months. After the first 35 minutes of HD,
lar fluid loss. With high gradients the she develops nausea and rigors and has a tem-
extracellular fluid compartment remains perature of 38.3 °C. Her BP drops from 157/80
expanded. It has thus been suggested that in to 100/61 mmHg, and her heart rate is 113
the management of dialysis patients with beats per minute, regular. She had a similar
intradialytic hypertension less steep dialysate- experience during dialysis 3 days ago, but the
to-plasma sodium gradients be maintained temperature was 37.7 °C and she had transient
and thus facilitate extracellular fluid loss. rigors. Examination revealed mild erythema
6. A 54-year-old with end-stage renal disease and tenderness of the exit site but no purulent
from lupus nephritis who was transferred discharge. No other patient having dialysis at
10 weeks ago from peritoneal dialysis to the centre has similar occurrence. What is the
hemodialysis following fungal peritonitis, has most likely cause of clinical scenario?
come into the HD unit with complaints of A. Gram positive infection
low-grade, continuous fever, malaise, and B. Gram negative infection
central chest pain. The pain is rather constant C. Fungal infection
and is mildly improved by a change in posture D. Virus infection
to a seated position. There is no associated E. Parasite infection
cough or dyspnea. A bedside 12-lead ECG The correct answer is C.
done showed features of LVH and non- This is most likely a catheter-related blood
specific ST segment changes, while an echo- stream infection and Gram positive organisms
cardiogram revealed mild pericardial effusion. like Staph Aureus are the commonest
White blood cell count was 14,000cells/mm3 organisms
while CRP was 62 mg/dL. B-D-Glucan assay
was indeterminate. A highly likely diagnosis Test your learning and check your understand-
in this patient is: ing of this book’s contents: use the “Springer
A. Uremic gastritis Nature Flashcards” app to access questions
B. Tietze’s disease using https://sn.pub/cz9Cok. To use the app,
C. Fungal pericarditis please follow the instructions in Chap. 1.
D. Lupus pericarditis
E. Dialysis pericarditis
The correct answer: E. References
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Peritoneal Dialysis
19
Angela Yee-Moon Wang

A 68-year old woman with long-standing diabe-
tes mellitus and stage 4 chronic kidney disease Peritoneal dialysis (PD) is one of the main kidney
(CKD), followed up at the renal clinic showed replacement therapies (KRT) that can be carried
gradual deterioration in kidney function over the out at home for patients with end stage kidney
last few years. In the past 6 months, her kidney disease (ESKD). To carry out PD, patients need
function has deteriorated further. She lives with to have a catheter placement into peritoneal cav-
her husband, and carries out her daily activities ity. Dialysis fluid is instilled into the peritoneal
independently, and also looks after her family. cavity through the catheter and allowed to dwell
Clinically, she is asymptomatic. On examination, for 4–6 h. Uraemic retention solutes are removed
her blood pressure is 150/95, she has a mild pal- through the semi-permeable peritoneal mem-
lor over her palmar creases and conjunctiva. Her brane by diffusion. Simultaneously, ultrafiltration
chest is clear on auscultation, but there is mild takes place through the peritoneal membrane,
bilateral pedal edema. Her blood tests show a with the dialysis fluid glucose acting as an
blood haemoglobin of 9 g/dL, her serum sodium osmotic agent. The peritoneal membrane charac-
142 mmol/L, and potassium 5.4 mmol/L, urea is teristics differ among patients and affect perito-
37.8 mmol/L, and creatinine 450 μmol/L, her neal membrane transport kinetics of fluid and
estimated glomerular filtration rate (eGFR) using solutes. Peritoneal membrane characteristics may
CKD-EPI equation is 8.1 mL/min/1.73 m2, her change over time in individual patients due to
serum bicarbonate is 19 mmol/L, serum albumin uremia, diabetes, dialysis procedure, dialysis flu-
is 35 g/L, and adjusted serum calcium is ids, drugs, peritoneal infections or inflammation.
2.34 mmol/L, and phosphate is 2.10 mmol/L. This chapter aims to give a practical guidance to
How would you counsel the patient about her clinicians delivering PD therapy. The topics
options for kidney replacement therapy? include: assessing and preparing kidney failure
patients for PD and contraindications to PD. A
brief description of the different PD modalities,
solutions, prescription, and key principles in
delivering high quality goal-directed PD will be
given. The chapter will outline assessments of
A. Y.-M. Wang (*) residual kidney function (RKF), indices of dialy-
Department of Medicine, Queen Mary Hospital, the
University of Hong Kong, Pokfulam, Hong Kong sis adequacy, peritoneal membrane transport
e-mail: angela_wang@connect.hku.hk characteristics as well as quality of PD therapy. A
https://doi.org/10.1007/978-3-031-09131-5_19
384 A. Y.-M. Wang
clinical approach to low clearance and low drain PD is contraindicated if the peritoneal cavity
volume in PD will be discussed. is obliterated or the membrane is not functional,
for example due to peritoneal adhesions or cath-
eter placement is not possible. Obesity may pres-
Assessing and Preparing Kidney ent a challenge but is not a contraindication to
Failure Patients for PD PD. Obese patients receiving PD may be at an
increased risk of catheter leak, hernias, exit site
The provision of pre-dialysis education and deci- infection, and peritonitis compared with non-
sion aids increase the likelihood of patients obese patients. A high body mass index may lead
choosing home dialysis therapy such as to inadequate solute clearance especially with
PD. Home dialysis or PD provides patients more loss of RKF, thus requiring larger dwell volumes.
freedom and flexibility with their time and In morbidly obese patient, an extended catheter
improves their sense of well-being. When being with a high abdominal or pre-sternal exit site may
told of the need for dialysis, patients very often be used to avoid placement in a skin fold or the
have difficulties accepting it and are fearful that pannus region, but this would require consider-
dialysis initiation might impact their work, able operator experience. A history of previous
personal life, travel and quality of life. Pre- abdominal surgery does not preclude percutane-

dialysis education provided by a multidisci- ous PD catheter placement unless extensive
plinary team of experienced staff plays an adhesions are present or anticipated. Polycystic
essential role in alleviating fear and anxiety of kidneys may increase intra-abdominal pressure
patients, help patients to better understand kidney and increase risk of hernias. However, PD has
failure, face and accept dialysis, make their pre- been successfully performed in these patients.
ferred choice of dialysis modality, prepare and Thus, the decision of modality choice in patients
cope with life on dialysis better and maintain a with polycystic kidneys need to be individual-
feeling of control with their health condition. ized, taking into consideration the enlarged kid-
Generally, patients should be referred to pre- neys and/or liver size, patients’ body build and
dialysis education at least 4–6 months before sense of abdominal fullness with the enlarged
dialysis initiation or when their eGFR falls below kidneys and/or liver. Patients with chronic consti-
15 mL/min/1.73 m. The multidisciplinary team pation, diverticular disease and other causes of
involved in giving pre-dialysis education should abnormal colonic distention may be unsuitable
include experienced nephrologist, renal nurse, candidates for PD. Patients with cirrhosis and
dietitian, physiotherapist, psychologist, and ascites are at an increased risk of spontaneous
social worker. The program should be designed bacterial peritonitis and protein loss, but PD is
according to local settings, culture, staff avail- not contraindicated. PD has been successfully
ability and patient load in individual hospitals. performed in these patients and the PD catheter
Lack of patient preparedness and an urgent start allows drainage of ascites.
to dialysis are associated with lower survival and
higher morbidity.
In assessing patients planning for PD therapy, Choice in PD Modality
a careful history should be taken in relation to
their co-morbidities, bowel habits, personal The choice of PD modality should be personal-
hygiene, and prior abdominal surgeries. Patients’ ized, involving a shared decision-making
general condition, ability to perform PD, family approach between physicians and patients and is
support and home environment need assessment. the modality that patient chooses after receiving
Assisted PD may be considered in elderly patients dialysis education and decision support. Patients
or patients with mental or physical disabilities and caregivers need to be informed of the chal-
who choose PD. lenges, considerations, and trade-offs of the dif-
19 Peritoneal Dialysis 385
ferent dialysis modalities so that modality which the modality has been chosen prior to the
selection can be tailored to their individual health need for dialysis and there is an access ready for
and social circumstances. use at the initiation of dialysis. An unplanned
start is dialysis initiation when access is not ready
for use or requires hospitalization or when dialy-
PD Catheter Placement sis is initiated with a modality that is not the
patient’s choice.
PD catheter can be placed by traditional open PD is possible in both planned or unplanned
surgical techniques, laparoscopic implantation, and urgent or nonurgent start. However, patients
or percutaneous insertion. Percutaneous insertion with hyperkalemia, volume overload, or marked
is preferred because it can be done under local uremia are not good candidates for urgent-start
anaesthesia, is less invasive and less costly. PD.
Physicians can be easily trained to perform per- The major barriers to an urgent-start PD pro-
cutaneous PD catheter insertion and this signifi- gram are lack of operators who can place a PD
cantly minimizes delays in arranging catheter catheter within the urgent start time frame and
insertions. Both laparoscopy and open surgery limited capacity of the health care facility to sup-
typically require general anaesthesia, are most port PD for urgent-start patients and nursing
costly and usually reserved for cases with manpower to train patients at short notice
previous abdominal surgeries. In placing a PD (Table 19.1). Where technical expertise in PD
catheter (double cuffed preferred), the catheter catheter placement is lacking, this can be
coil must be positioned in the most dependent addressed by increasing training of nephrolo-
region of the peritoneal space: the posterior low gists. In urgent start, PD patients may have lim-
pelvis. Meticulous attention should be placed to ited time to receive required education for an
the location of the catheter exit site, creation of informed decision making on their initial choice
an inferiorly angled tunnel through the rectus of modality. These patients need to be provided
abdominis muscle, and establish a stable position with the required education and support to enable
of catheter coil within the pelvic cul-de-sac. transition to their preferred modality when
Prophylactic antibiotics should be given prior to feasible.
catheter operation. After catheter placement, a Starting PD exchanges shortly after PD cath-
breathable dressing must completely cover the eter placement instead of waiting for 2 weeks
abdominal incision wound and catheter exit site. period for the cuff ingrowth and abdominal
Both the wound and exit site dressing should be wound healing requires treatment modifications
kept dry and intact. Unless the catheter is used include doing intermittent PD in hospital in
immediately as part of an urgent-start program, a
minimum 2-week healing time is needed to
ensure tissue ingrowth of the catheter cuffs and
Table 19.1 Institutional infrastructure setup required for
prevent fluid leaks prior to starting PD. urgent-start PD programs
(i) Ability to place a peritoneal catheter immediately
within 48 h;
Urgent Start PD (ii) Staff education regarding use of catheter
immediately after placement;
Urgent start PD is defined as the situation in (iii) Administrative support in inpatient and outpatient
settings;
which PD needs initiation in less than 48 h after
(iv) Identification of appropriate candidates for
presentation to correct life-threatening complica- urgent-start PD;
tions. Non-urgent start refers to those in which (v) Utilization of protocols in every step of the
dialysis initiation can be delayed more than 48 h urgent-start process from patient selection for PD
after presentation. A planned approach is one in through appropriate post-discharge follow-up.
386 A. Y.-M. Wang
recumbent position and reducing instillation vol- (ii) inability to control volume status or blood
ume to prevent leaks. pressure;
(iii) progressive deterioration in nutritional sta-
tus refractory to interventions.
I nitiation of PD Therapy for End-
Stage Kidney Disease Initiation of PD therapy should not solely be
based on numerical values of eGFR.
For patients who choose PD modality, initiation
of therapy should be considered when one or
more of the following are present: PD Modalities
(i) symptoms or signs attributable to kidney PD can be performed manually or via automated
failure (e.g., neurological signs and symp- system. Continuous ambulatory peritoneal dialy-
toms attributable to uremia, pericarditis, sis (CAPD) is done manually. Automated perito-
anorexia, medically resistant acid-base or neal dialysis (APD) includes: continuous cyclic
electrolyte abnormalities, reduced energy peritoneal dialysis (CCPD), intermittent perito-
level, weight loss with no other potential neal dialysis (IPD), tidal peritoneal dialysis
explanation, intractable pruritus, or (TPD). Details of the different modalities are out-
bleeding); lined in Table 19.2.
Table 19.2 A Summary of Different forms of PD modalities prescription

CAPD Introduced in 1976 by Popovich and Moncrief and later modified by Oreopoulos as a wearable,
portable form of dialysis, not requiring any equipment other than the disposable PD solution bags and
a tube connecting the bag to patient’s PD catheter to instill PD fluids into patient’s peritoneal cavity.
Prescription can be modified based on clinical status, sense of well-being, nutrition status, volume and
blood pressure control, dietary compliance, biochemical parameters and indices of dialysis adequacy,
taking into account patient’s work and lifestyle pattern.
Prescription can be initiated with 1.5% 2 L × 2 or 3 exchanges and one night time exchange of around
8–10 days, taking into consideration patient’s body build, amount of RKF, urine volume and dietary
intake.
CAPD can maintain a relatively steady physiological state, control volume status and blood pressure
in most patients.
APD Automated PD was introduced in the late 1970s with an aim to achieve higher solute and fluid
removal than CAPD and to automate PD with a cycler during patient sleep time.
CCPD Continuous PD performed using a cycler. Typical prescription includes 3–4 night time exchanges each
of 2–3 L, depending on body build, clearance needs and residual kidney function (RKF) and a single
long day dwell with 1.5–2 L PD fluid.
It allows more flexibility in the number and volume of exchanges carried out during night time, and
reduces to a single daytime exchange, allowing patients more free time during the day. CCPD also
allows larger volumes to be used in the supine position and minimizes the risk of touch contamination.
IPD Usually consists of frequent, short cycles performed over 12–24 h per session and peritoneal cavity
was drained dry between sessions. Nocturnal IPD (NIPD) is performed nightly and is usually reserved
for patients with high peritoneal solute transport and low ultrafiltration. The short cycles of NIPD
allow better ultrafiltration than longer cycles of CAPD or CCPD in high transporter. The total PD
exchange volume per treatment usually ranges between 8 and 12 L.
PD Plus PD Plus refers to CCPD with an exchange added to the long day dwell hours. Usually 3 or 4 × 2 L PD
exchanges are performed during the night for 8–10 h. The long day dwell is then split into two shorter
daytime exchanges performed manually or cycler assisted to improve both clearance and
ultrafiltration. It limits daytime exchanges to less than 7 h. It is usually used for patients of larger body
build, anuric patients or patients who need more solute clearance.

TPD It consists of an initial fill usually in the range of 2–2.5 L then a variable dwell and partial drain,
usually half of the PD volume, leaving a residual volume in the peritoneal cavity. The cavity is refilled
and this will repeat until the last exchange when all PD fluids are drained. There is usually a daytime
exchange.
The principle purpose of TPD is to enhance clearance of small solutes by reducing the normal loss of
dialysis time with inflow and outflow of PD fluid. However, TPD has not been shown to be superior to
APD in terms of clearance or ultrafiltration.
TPD may be useful for patients with inflow or outflow pain, slow drainage or multiple alarms due to
drainage problems. It is more costly and complex to implement.
Assisted PD It is usually adopted in patients of which a caregiver, helper or nursing staff is required to carry out the
PD procedure such as in elderly patients, patients with multi-morbidities who are unable to do the
procedure themselves or those in aged home. It can be done either manually by CAPD or using a
cycler.
Incremental A strategy by which less than standard full dose PD is prescribed in patients starting PD treatment
PD and the combination of RKF and peritoneal clearance achieved remains sufficient to achieve
individual clearance goals. It can be adopted in patients with relatively well preserved RKF. It
incurs less workload for patients and their caregivers to do PD, thus enabling them more free time
for life participation. It also has the advantage of minimizing patients’ exposure to glucose
solutions. Incremental PD is more cost-saving for emerging countries.
PD Solutions With high lactate, high glucose concentration,

high osmolality and high levels of glucose degra-
Constituents of PD Solutions dation products (GDPs) generated, long term use
of these solutions are associated with progressive
Commercially available PD solutions contain peritoneal membrane injury, neovascularization,
sodium (132–135 mmol/L), calcium (1.25– peritoneal sclerosis and fibrosis. The low pH,
1.75 mmol/L), magnesium (0.5 mmol/L), chlo- high osmolarity and high glucose content of these
ride (95–103.5 mmol/L) and lactate solutions also inhibit phagocytic functions of
(35–40 mmol/L) and varying concentrations of peritoneal leukocytes and impair host immune
glucose/dextrose ranging from 1.36%/1.5%, defense mechanisms. Some patients may com-
2.27%/2.5% and 3.86%/4.25%. The overall plain of inflow pain with these solutions.
osmolality was 344–347, 395–398, and 483–486 Calcium concentration of these solutions var-
mOsmol/L, respectively and aimed to facilitate ies between 1.25 and 1.75 mM with 1.75 mM
ultrafiltration and removal of water-soluble ure- being termed standard calcium and 1.25 mM
mic toxins through the peritoneal membrane being termed ‘low calcium’ but 1.25 mM is the
while maintaining electrolyte and acid-base bal- more physiological calcium concentration. Use of
ance of PD patients. 1.75 mM calcium dialysate is associated with
Standard glucose solutions are acidic in pH more progression in coronary artery calcium
(5.0–5.8) to prevent dextrose caramelization dur- score over 24 months than 1.25 mM calcium dial-
ing the sterilization procedure. Lactate concen- ysate in hemodialysis, especially with poor phos-
tration varies between 35 to 40 mmol/L. Lactate phorus control. Furthermore, use of 1.25 mM
is rapidly metabolized to bicarbonate in a 1:1 calcium dialysate showed a significantly lower
ratio in patients with normal liver function and prevalence of histologically diagnosed low bone
maintains a high dialysate to plasma lactate con- turnover than 1.75 mM calcium dialysate group.
centration gradient required for continued Although similar study is not available in PD
absorption without lactate accumulation in the patients, Kidney Disease Improving Global out-
circulation. comes (KDIGO) 2017 CKD-mineral bone dis-
388 A. Y.-M. Wang
ease (MBD) guideline and International Society atherogenic visceral fat, weight gain, dyslipid-
of Peritoneal Dialysis (ISPD) Adult Cardiovascular emia and worsening glycemic control in PD
and Metabolic guideline 2015 suggested the use patients with diabetes.
of 1.25 mM calcium-containing PD solution to The standard heat sterilization of glucose-
avoid positive calcium balance or hypercalcemia. based solutions accelerates the generation of
GDPs. Glycated local proteins form advanced
glycation end-products (AGEs). Both GDPs and
Types of PD Solutions AGEs are directly cytotoxic to the peritoneal
mesothelial cells and contribute to the long-term
Glucose-Based Solutions bio-incompatibility of glucose-based solutions
The ultrafiltration rate across the peritoneum is (Fig. 19.1). They cause mesothelial cell loss,
directly proportional to the initial glucose inflammation, submesothelial fibrosis and thick-
osmotic gradient (Table 19.3)
Table 19.3 Ultrafiltration volume with different glucose
dverse Effects of Glucose-Based PD
A concentrations
Solution Glucose solution Average ultrafiltration
Cumulative glucose absorption through the peri- concentration volume (mL)
toneum incurs negative effects to the peritoneum 1.36%/1.5% 100–200
and systemically including worsening of insulin 2.27%/2.5% 200–400
resistance, hyperglycemia, accumulation of 3.86%/4.25% >400
Intraperitoneal Glucose
Intraperitoneal (local) Effects Systemic Effects
Glycemic Control Carbohydrate/caloric load

Glucotoxicity Glucose Hyperosmolality
100-200 g glucose/day
Degradation
320-640 kCal/day
Products
Polyol pathway
Visceral Fat Mass

Hexosamine pathway
Changes to Peritoneal Membrane Dyslipidemia
Structure and Function Protein Kinase C pathway
AGE pathway
Fluid overload
Inflammation
Increased Cardiometabolic Risk?
Fig. 19.1 Negative local and systemic impact of peritoneal glucose

ening, calcification, vasculopathy and diabeti- lucose Polymer Solution or Icodextrin

G
form neoangiogenesis, resulting in changes to the Icodextrin is a starch-derived, branched, water
peritoneal membrane structure and increased soluble glucose polymer with an average molec-
peritoneal solute transport (PSTR) with time on ular weight between 13,000 and 19,000 Daltons.
dialysis, requiring use of higher glucose concen- Commercially available 7.5% icodextrin solu-
tration solutions for ultrafiltration. This would tion has a sodium concentration of 133 mmol/L
eventually lead to peritoneal membrane failure and a lactate concentration of 40 mmol/L and is
(PMF) over time and increase risk of volume iso-osmotic (284 mOsmol/L). Icodextrin is not
overload. A high PSTR is associated with worse significantly metabolized in the peritoneum and
patient survival and a trend towards worse PD is slowly absorbed into the bloodstream via the
technique survival. Thus, a glucose sparing or lymph vessels, with around 40% being absorbed
glucose minimization PD regimen should be after a 12 h period and is metabolized into oli-
adopted in all PD patients as clinical condition gosaccharides and maltose by circulating
and financial situation permit. α-amylase (Fig. 19.2). Maltose cannot be
Almost two thirds of the PD fluid glucose are metabolized in the circulation of humans as
absorbed during a 4-h dwell and over 85% in an maltase is not in the circulation but is present in
8-h dwell with an average PSTR. This translates the kidney and intracellularly in the body. As
to an obligatory absorption of 43 g and 73 g of icodextrin does not get reabsorbed, it is a supe-
glucose with an 8-h dwell of 2.5% and 4.25% rior osmotic agent and has superior ultrafiltra-
solutions, respectively. Exposure to glucose- tion capacity than glucose solution, especially
based PD solution is associated with more weight when dwell for long hours.
gain, truncal fat mass and visceral adiposity Icodextrin is a useful salvage therapy in PD
increase than use of non-glucose-based PD solu- patients with refractory fluid overload or ultrafil-
tions. Increased abdominal adiposity also con- tration failure and may prolong PD technique
tributes to a higher cardiovascular risk in PD survival (Table 19.4). PD patients using icodex-
patients. High glucose solutions may also add trin achieved significantly better daily peritoneal
satiety and reduce appetite. ultrafiltration and had lower incidence of uncon-
15 ml UF per gram absorbed
SHORT
“LONG DWELLS”
1200 DWELL
1000 4.25% glucose

800
600
Net UF (mL)
11 ml UF per gram absorbed

400
200 7.5% Icodextrin 3 ml UF per gram absorbed
0
–200 Osmotic agent absorption
–400
CAPD APD
–600
Overnight Daytime
–800
0 2 4 6 8 10 12 14
Time (hr)
Fig. 19.2 Ultrafiltration profile of Icodextrin

390 A. Y.-M. Wang
Table 19.4 Current recommendations for icodextrin use eutral pH Low-GDP Solutions
N
• Icodextrin is recommended to improve ultrafiltration Epithelial-to-Mesenchymal transition (EMT) of
independent of the dialysate to plasma creatinine peritoneal mesothelial cells is a hallmark feature
ratio [ISPD 2020 guideline].
in the peritoneum of PD patients and plays a
• Icodextrin should be used as the long dwell in high
transporter patients with a net peritoneal mechanistic role in the initiation of peritoneal
ultrafiltration <400 mL during a PET with a 3.86% fibrosis, leading onto peritoneal membrane func-
glucose solution [European Best practice working tion decline and failure.
group].
Bicarbonate is the most physiologic and bio-
• Once daily icodextrin should be considered as the
long-dwell dialysis solution in diabetic peritoneal compatible buffer. However, calcium and magne-
dialysis patients for better glycemic control (2C) sium precipitate with bicarbonate in alkaline
[ISPD 2015 guideline]. pH. The biocompatible PD solution adopts a
dual-chamber dialysate bag in which one cham-
ber contains the bicarbonate buffer of 34 mmol/L
trolled fluid overload than standard glucose PD and the other contains a solution with calcium
solutions without compromising RKF. and magnesium. The two solutions are mixed
Icodextrin as the long-dwell solution mini- together only prior to instillation into patients’
mizes glucose exposure and absorption, and abdomen to prevent calcium and magnesium car-
incurs less metabolic disturbance compared to bonate precipitation. It allows heat sterilization
glucose solutions. Icodextrin improves glucose and storage occurring at a lower pH in a separate
metabolism, insulin sensitivity and reduces dys- bag and minimizes generation of GDPs. Some of
lipidemia compared to glucose solutions. It has the low GDP solutions used bicarbonate instead
been shown to reduce insulin requirement, lower of lactate as buffer. Mixing the contents of the
fasting glucose, improve glycated hemoglobin, two chambers just before use produces a more
lower serum triglycerides and has fewer adverse physiological solution with a neutral pH of
events than glucose solution in diabetic PD around 7.0.
patients. It also reduces insulin resistance index The use of neutral pH, low GDP solutions was
in non-diabetic PD patients. Icodextrin did not associated with better preserved peritoneal mem-
adversely impact on RKF. brane morphology, function, better host immune
Adverse effects of icodextrin may include defense and less systemic inflammation and is
sterile or chemical peritonitis or skin rash as a effective in ameliorating metabolic acidosis. The
result of allergy to starch (around 10%). Sterile Cochrane systemic review of several randomized
peritonitis with icodextrin IS related to contami- trials concluded that neutral pH, low GDP solu-
nation of icodextrin by peptidoglycan which is a tions was associated with better preservation of
constituent of bacterial cell walls. Clinically, RKF and greater urine volumes when used for
patients with sterile or chemical peritonitis may 12 months or more and also beyond 12 months
remain well despite having cloudy effluent. The though less significant. Peritonitis rates did not
differential cell count of PD fluid shows differ between neutral pH, low GDP solutions
predominantly eosinophilia but not neutrophils. and standard glucose solutions. A trend towards
PD effluent usually clears up rapidly on with- lower ultrafiltration volume and lower incidence
drawal of icodextrin. of inflow pain was observed with neutral pH low
Icodextrin and its metabolites may interfere GDP solutions compared to standard glucose
with some laboratory analytical methods on plasma solutions but not reaching statistical significance.
glucose measurements. Glucometers that use glu- There is no data to show that this solution impacts
cose dehydrogenase-pyrroloquinolinequinone patients’ survival. Table 19.5 lists the current rec-
overestimate blood glucose in patients using ommendations for use of neutral pH, low GDP
icodextrin. solutions.
Table 19.5 Current recommendation for Neutral pH, Table 19.6 Factors affecting clinical outcomes of PD
low GDP solutions patients
• Neutral pH, low GDP solutions is recommended Factors Impact
for better preservation of RKF if used for Age Impaired physical function
12 months or more [ISPD 2015 and 2020 Impaired cognitive function, dementia /
guidelines]. delirium
Protein energy wasting
mino Acid Solutions
A Falls, frailty
The 1.1% amino acid solution contains Multi- Symptoms
morbidity Polypharmacy
87 mmol/L of amino acids, 61% of which is Impaired physical function
essential amino acids. The nitrogen absorbed Impaired cognitive function
from a single daily dwell of 1.1% amino acid Protein energy wasting
solution is sufficient to offset the daily losses of Dialysis- Symptoms
related Infections
amino acids and protein from the peritoneum
Polypharmacy
which may mount up to 3–4 g of amino acids and Volume status—volume overload or
4–15 g of proteins per day even in stable condi- depletion
tion. This amount may increase further with peri- Protein energy wasting
Burden of dialysis
tonitis. Usually, around 72–82% of amino acids
Psycho-social Depression
are absorbed in a single daily dwell and this may Anxiety
amount up to 18grams a day, thus providing a Financial stress
good source of protein supplement without add- Social support
ing phosphorus load. It provides an ultrafiltration
volume comparable to that achieved with 1.36%
glucose solutions. The peak plasma amino acid Pattern (PDOPPS) showed a lot of variations in
concentration is usually achieved around an hour. PD prescription in terms of modalities, types of
Compared to glucose solution alone, com- PD solutions and PD regimens around the world.
bined amino acids and glucose PD solutions have Indeed, the modality of PD should be individual-
been shown to improve protein kinetics and ized according to the patients’ need, peritoneal
whole body protein synthesis. 1.1% amino acids transporter characteristics and RKF (Table 19.6).
solution has confirmed safety. Potential adverse
effects include nausea and anorexia. Some
patients may develop mild metabolic acidosis. Key Principles in PD Care Delivery
This may be ameliorated by adjusting to using a
bicarbonate-based solution in the other The ISPD 2020 guideline recommended that PD
exchanges. The overall clinical benefit of 1.1% prescription should be ‘goal-directed’ and should
amino acid solution on nutrition status has involve shared decision-making in establishing a
remained equivocal. It may be reserved as a personalized realistic care goal that maintains
glucose-sparing solution and for use in subjects quality of life for the person doing PD as much as
at risk or exhibit features of PEW syndrome. possible, enables them to meet their life goals,
minimize symptoms and treatment burden while
ensuring the delivery of high-quality care. Patient
D Prescription in Terms of Choice
P reported outcomes are crucial measures of the
of PD Modality, PD Solutions effectiveness of patient centered care. Patients
and Doses should have the opportunity to report them and to
receive the required symptom evaluation and
For years, PD prescription has been focused on management in order to improve the care they
small solute clearance and urea clearance (Kt/V) received.
has been used as a target in defining dialysis ade- Patients doing PD should be educated and
quacy. The Peritoneal Dialysis Outcome Practice given choice as far as is possible concerning the
392 A. Y.-M. Wang
PD prescription they receive. Patients doing PD assessment of patient’s symptoms, experi-

should be educated about their condition and be ence, patient reported outcome measures
informed about their prognosis and be given the (PROMS), impact of the dialysis treatment
opportunity to define their goals of care. PD can regimen, and the psychosocial status of the
be prescribed in a variety of ways and should take patient. Treatment should be adjusted and
into account local resources, person’s wishes modified based on patients’ HRQOL, includ-
regarding lifestyle and the family’s/caregivers’ ing symptom management, adjustments in
wishes if they are providing assistance (Fig. 19.3). dialysis treatment regimens, and clearly
PD infection, cardiovascular disease, mortality, defining the goals of care.
PD failure and life participation were ranked the
top core outcome domains in the Standardized
Outcomes in Nephrology (SONG) initiative by
Table 19.7 Domains to be addressed in patients receiv-
all stakeholders (Table 19.7). ing PD
The following assessments should be included Cognitive dysfunction Uremic pruritus
to ensure high-quality PD care. Family and marital discord Anorexia, nausea
Depression Restless legs
(a) Patient reported outcome measures assess Anxiety Satisfaction with dialysis
treatment regimen
how a person doing PD is experiencing life
Fatigue Impact of the treatment
and his/her feeling of well-being. It should regimen on their life
take into consideration the person’s symp- Lethargy Satisfaction with care
toms, impact of the PD regimen on the per- provided
son’s life, mental health and social Physical functioning Caregiver burden
circumstances. Sexual dysfunction Abdominal discomfort,
anorexia appetite, nausea,
According to the ISPD 2020 guideline, vomiting
patient’s perception of their health-related Symptoms of neuropathy Additional physical
quality of life (HRQOL) should be assessed symptoms
routinely. This should take into account Sleep disturbances
Prescribing Peritoneal Dialysis For High Quality Care
Potential Elements To Consider Potential Interventions in the context of Evaluation

available resources
Functional Status and Cognition Initial and longitudinal PD prescription interventions

• PD modality (APD vs. CAPD)
Social (i.e. travel, employment, carer stress) • PD exchange volume (frequency and length Shared Decision Making to Evaluate Interventions in
• Treatment time and days per week context of Priorities and Establish or Revaluate Goals of
Patient Reported Outcomes (i.e. QCL, symptoms) Care
• Solution type(s)
• high/low/ultra-low ODP.
• neutraloid pH.
Residual Kidney Function • icodextin
• amino acid
• bicarbonate/lactate buffer
Volume Status / Blood pressure/Cardiac • gluccolacium/magnesium/socdium concentration Potential Goals of Care:
Geometry • Cycler type and use of remote patient monitoring • Improve survival
• Connectology • Extend time on PD therapy
Anemia • Tidal vs complete exchange • Increase quality of life
• Increase in Life Participation Activities
Bone Mineral Disorder Parameters • Symptom-Specific improvement
• Reduce hospitalizations
Electrolytes (i.e. acid-base, urate, sodium,
Consider Non-dialytic interventions Other Factors
• Address comorbid disease/intlercurrent iness • Prolong residual kidney function
potassium) • Anemia management (Iron, ESA, novel agents)
• Nutritional management
Nutrition – Protein Energy Wasting • Other lifestyle factors (physical activity, exercise)
• Mood disorder, Anxiety disorders treatment Goals of Care Achieved
• Non-dialytic management of bone mineral parameters
Metabolic Parameters: (i.e. Body composition/ • Address care partner burnout, familial issues
Body Mass Index, lipids, glycaemic control) • Non-dialytic management of bone mineral parameters
• Address care partner burnout, familial issues No Yes
Markers of systemic peritoneal Inflammation • Non-dialytic acid base/Electrolyte correction
• Bowel function (especially constipation)
• Sexual function,
Peritoneal membrane function • Non-dialytic management of other ESKD • Consider alternative renal
complications/symptoms (restless legs, pruritus, sleep replacement therapy
Small Solute Clearance disorders, muscle cramps, fatigue, gout, dysgeusia) • Consider non-dialytic
• Treatment adherence
management, comprehensive
Clearance of other uremic toxins (i.e. middle • Monitor of encapsulating peritoneal sclerosis risk/diagnosis
conservative care
molecules protein bound)
Fig. 19.3 Prescribing high quality PD

(b) Volume status is an important part of PD The diagnosis of PEW is made based on the
delivery. Urine output and fluid removed by presence of three out of the four characteristics
PD both contribute to euvolemia. Regular listed in the table above. Unintentional weight
assessment of volume status, including blood loss should lead one to consider the presence
pressure and clinical examination, should be of PEW. Loss of 5% of non-edematous weight
part of routine PD care. within 3 months or an unintentional loss of
(c) Nutrition status should be assessed regularly 10% of non-edematous weight over the past
through evaluation of the patient’s appetite, 6 months is an indicator of PEW, independent
clinical examination, body weight measure- of weight-for-height measures. Loss of body
ments and blood tests (potassium, bicarbon- fat and muscle mass are considered as impor-
ate, phosphate, albumin). Dietary intake of tant criteria for diagnosing PEW. Inflammatory
potassium, phosphate, sodium, protein, car- markers such as C-reactive protein are usually
bohydrate and fat may need to be assessed elevated in the setting of PEW.
and adjusted as well. (d) Removal of uremic solutes may be estimated
Various nutritional indices including body using Kt/Vurea and/or creatinine clearance.
weight changes, appetite, subjective global Both are measures of small solute clearance.
assessment (SGA), serum albumin, handgrip
strength may be used.
Hypokalemia is associated with poor Residual Kidney Function
nutritional status and adverse outcomes
including peritonitis. Hypoalbuminemia is RKF is an important parameter in predicting
more common in PD than hemodialysis and clinical outcomes of PD patients and its contri-
is associated with PEW and peritoneal pro- bution is stronger than PD clearance. Having a
tein losses (Table 19.8). Hyperphosphatemia better preserved RKF is associated with better
is multifactorial and associated with adverse small solutes and middle molecule uremic
outcomes in PD. Factors to consider include retention solutes clearance, better extracellular
patients’ dietary intake, compliance to phos- volume control, less inflammation, better con-
phate binders, RKF and PD prescription. trol of CKD-bone mineral disease, better nutri-
tion status and less resting hypercatabolism,
Table 19.8 International Society of Renal Nutrition and thus contributing to overall better survival and
Metabolism Consensus Criteria to diagnose protein- cardiovascular outcomes and better quality of
energy wasting (PEW) life (Fig. 19.4). PD patients with faster decline
Dietary intake in RKF or urine volume were associated with
Unintentional low dietary energy intake <25 kcal/kg/ worse patient survival and technique survival.
day for at least 2 months
Unintentional low dietary protein intake <0.8 g/kg/
It is therefore imperative to measure urine vol-
day for at least 2 months ume or RKF regularly in PD patients
Body mass (Table 19.9).
Body mass index <23 kg/m2
Unintentional weight loss over time: 5% over
3 month or 10% over 6 month
reserving Residual Kidney Function
P
Total body fat <10%
Muscle mass
in PD Patients
Muscle wasting: Reduced muscle mass 5% over 3 m
or 10% over 6 month It is generally recognized that avoid over-
Reduced mid-arm muscle circumfrence area >10% dehydration and hypotensive episodes as well as
in relation to 50th percentile of reference population avoid nephrotoxins and iodinated contrast use
Creatinine appearance
may be important. Diuretics increases urine vol-
Serum biochemical parameters
Serum albumen <38 g/L (bromcresol green method)
ume and sodium excretion and minimizes use of
Serum prealbumin (transthyretin) <300 mg/L hypertonic PD glucose solutions but did not pre-
Serum cholesterol <100 mg/L serve RKF.
394 A. Y.-M. Wang
↓ Residual renal
function
↓ Removal of
↓ Erythropoietin ↓ Urea and
↑ Resting energy middle molecule ↑ ↓ Sodium and ↓ Phosphorus
production and creatinine
expenditure uremic toxins, for Inflammation fluid removal removal
anemia clearance
example, p-cresol
Cardiac hypertrophy Atherosclerosis and Vascular and valvular

Malnutrition and heart failure arteriosclerosis calcification
↑ Overall and cardiovascular mortality
↓ Quality of life and well-being
Fig. 19.4 Importance of RKF
Table 19.9 Recommendations on RKF APD versus continuous form of PD may influ-
• RKF should be monitored at least once every ence the rate of decline in RKF differentially.
6 months in PD patients with urine output
• Management should focus on preserving RKF as
long as possible in PD patients.
Assessment of RKF
Neutral pH, low GDP biocompatible PD solu- Residual glomerular filtration rate (GFR) is esti-
tion was associated with better preserved RKF mated by averaging 24-hour urine urea and cre-
and greater urine volumes for use greater than atinine clearance and is normalized to body
12 months. The ISPD Adult Cardiovascular and surface area. Unmodified urine creatinine clear-
Metabolic Guidelines recommended that neutral ance substantially overestimates the true GFR
pH, low GDP solutions should be considered for due to tubular secretion of creatinine while renal
better preservation of RKF if used for 12 months urea clearance underestimates GFR. At a mini-
or more (2B). On the other hand, glucose poly- mum, urine volume should be measured and
mer or icodextrin solution has no significant tracked regularly.
effect on RKF in PD patients (Fig. 19.5).
Two very small trials suggested better preser-
vation of RKF with angiotensin converting ssessment of Indices of Dialysis
A
enzyme inhibitors or angiotensin receptor block- Adequacy
ers. A small trial suggested benefit of ketoacid
supplemented low protein diet in preserving RKF ‘Dialysis adequacy’ is used to denote small sol-
in PD patients. Two small single-arm pilot stud- ute clearance, namely urea clearance normalized
ies suggested that oral N-acetylcysteine 1200 mg to total body water (Kt/V) and creatinine clear-
twice daily for 2–4 weeks may be useful in ance, normalized to body surface area (CrCl)
increasing urine volume and residual GFR. These (150) in PD patients. Both are comprised of two
preliminary findings need further confirmation in components, namely clearance from RKF and
adequately powered RCTs. There is no c onclusive clearance from PD. Kt/V and CrCl are estimated
evidence to suggest the modality of PD, namely from the urea and creatinine output from the
Avoid
nephrotoxic
drugs
Use
Prevent PD biocompatible
peritonitis solutions
Preserve
RKF
Use Use ACE
radiocontrast inhibitors/
judiciously ARBs
Avoid
Optimise BP hypotension
control and
dehydration
Fig. 19.5 Potential therapeutic strategies that may preserve RKF
drained effluent and urine collected during a stimation of Normalized Protein

E
simultaneous 24 h period together with a blood Nitrogen Appearance (nPNA)
sample collected for serum urea and creatinine.
Both Kt/V and CrCl values are conventionally nPNA, a surrogate of dietary protein intake can
expressed as weekly. In APD, the effluent vol- be estimated using the Randerson formula.
umes involved may be larger. APD patients are However, the equation assumes that the patient is
usually trained to record or measure total effluent metabolically stable and urea generation, excre-
volumes at home using the machine reading and tion and other nitrogen losses are proportional
bring back a representative aliquot of the dialy- and in equilibrium to the amount of protein
sate to clinic for measurement of urea and creati- intake. These formulas are derived using the
nine concentrations. same variables as Kt/V (Table 19.10).
In CAPD, serum urea and creatinine may not Kidney Disease Outcome Quality Initiative
fluctuate much during the day and the timing of (KDOQI) 2020 recommended a dietary protein
blood sampling for urea and creatinine may not intake of 1.0–1.2 g /kg body weight for metaboli-
be as critical. In APD, however, serum urea and cally stable PD patients to maintain a stable nutri-
creatinine may vary 10% or more from a trough tional status. A daily energy intake of 25–35 kcal/
value after stopping PD in the morning to peak kg ideal body weight per day (including energy
levels before patient resumes PD in the evening. derived from peritoneal glucose absorption)
Thus, in patients receiving APD with no day based on age, gender, level of physical activity,
dwell, serum samples should be collected approx- body composition, weight status goals, CKD
imately half way between the hours with no day stage, and concurrent illness or presence of
dwell. inflammation to maintain normal nutritional sta-
396 A. Y.-M. Wang
Table 19.10 Summary of various equations glucose concentration at 4 h to 0 h are estimated

nPNA by 10.76a(UNA/1.44 + 1.46) and UNA is in together with ultrafiltration volume at 4 h. The
Randerson g/day peritoneal transport characteristics are defined
Residual Average of (24 h urine urea
accordingly (Fig. 19.6).
GFR clearance + creatinine clearance in mL/
min) Generally, urea clearance is much less affected
Total Kt/V Summation of PD Kt/V and renal Kt/V by peritoneal transport characteristics than CrCl in
PD KT/V [(24 h PD volume in L)a(24 h PD fluid CAPD as over 90% of Kt/V and equilibration
urea concentration in mmol/L)/Plasma occurs with the long dwell hours of CAPD, regard-
urea concentration in mmol/L] and
normalized by V
less of peritoneal transport characteristics.
Renal Kt/V [(24 h urine volume in L)a(24 h urine urea Peritoneal membrane transport characteristics is
concentration in mmol/L)/Plasma urea an important consideration in PD modality (APD
concentration in mmol/L] and normalized versus CAPD) and regimen prescription as creati-
by V nine clearance may show two to three times differ-
Total CrCl Summation of PD CrCl and renal CrCl
ence between low and high transporters even after
PD CrCl [(24 h PD volume in L)a(24 h PD fluid
creatinine concentration in umol/L)/ a 4–6 h dwell. In APD, dwell time is usually
Plasma creatinine concentration in shorter than CAPD except for the long day dwell.
umol/L] and normalized by BSA In anuric PD patients, there could be problems in
Renal CrCl [(24 h urine volume in L)a(average of 24 h achieving optimal clearance targets, depending on
urine urea and creatinine concentration in
umol/L)/Plasma creatinine concentration the peritoneal membrane transport characteristics.
in umol/L] and normalized by BSA
V 2.447 + (0.3362 × BW in
kg) + (0.1074 × BH in I s There a Target for Small Solute
cm) − (0.09516 × age in years) for male
−2.097 + (0.2466 × BW in
Clearance?
kg) + (0.1069 × BH in cm) for female
BSA 0.007184 × BW in kg 0.425 × BH in cm 0.725 Two large prospective RCTs did not observe any
UNA Urea nitrogen appearance, V Total body water esti-significant benefit on overall survival of PD
mated by Watson method, BSA Body surface area, BW patients by increasing peritoneal small solute
Body weight, BH Body height clearance. In the Adequacy of PD in MEXico
a
These equations assumed a steady state, where urea nitro-
gen output equals to urea generation. The Randerson (ADEMEX) study, increasing weekly Kt/V from
1.62 to 2.13 (or weekly CrCl from 46.1 to 56.9 L/
equation assumed the average daily dialysate protein loss
wk. per 1.73 m2) had no significant effect on mor-
is 7.3 g per day. In PD patients with substantial protein
losses in dialysate or urine, these losses must be added to
tality risk in PD patients. In the randomized trial
the equation in calculating nPNA
from Hong Kong of which PD patients were ran-
domized to Kt/V targets of 1.7–2.0 and >2.0. no
tus is recommended for metabolically stable PD significant difference was observed in the overall
patients. survival between the group reaching Kt/V target
of 1.7–2.0 and the group reaching Kt/V >2.0.
There is no data to support benefit of further
Peritoneal Equilibration Test (PET) increasing total weekly Kt/V beyond 2.0 or total
CrCl of over 60 L/week per 1.73 m2.
It is a simple bedside test that assesses the diffu- The 2 trials raised important questions about
sive transport capacity of urea, creatinine and previous focus on achieving small solute clear-
other solutes and ultrafiltration across the semi- ance targets in PD care delivery. In the 2020 ISPD
permeable membrane. It involves doing a 4 h guideline, high quality goal-directed PD should
dwell with a 2 L bag of 2.5% PD solution during aim to achieve and maintain clinical euvolemia
which the ratio of dialysate to plasma creatinine and blood pressure while taking RKF and its pres-
concentration at 4 hour and the ratio of dialysate ervation into consideration, as well maintain good
a 1.2
b 1.2
Slow Slow
Low average Low average
1.0 1.0
High average High average
Rapid Rapid
0.8 0.8
D/Do
D/Do
0.6 0.6
0.4 0.4
0.2 0.2
0.0 0.0
0 1 2 3 4 0 1 2 3 4
Glucose Creatinine
Fig. 19.6 Peritoneal equilibration test
Fig. 19.7 Factors to be

reviewed in patients who Hypokalaemia
remain symptomatic
despite achieving a Kt/V Review PD
>1.7 Protein energy wasting
prescription and
other non-
Hypoalbuminemia dialysis related
factors
Hyperphosphatemia
nutrition status, perceived well-being and quality There was weak evidence to suggest that
of life of PD patients so for their life participation anuric PD patients should have a weekly Kt/V of
and not for the role purpose of reaching an arbi- at least 1.7. In the NECOSAD (Netherlands
trary numerical clearance target. Cooperative Study on the Adequacy of Dialysis)
Patients who remain symptomatic despite a observational Study, peritoneal Kt/V <1.5 and
Kt/V >1.7 should have other dialysis and non- CrCl <40 L/week per 1.73 m2 were associated
dialysis related factors reviewed as possible con- with higher mortality (175).
tributing factors. In emerging countries, every In elderly patients who are frail or have a poor
effort should be made to conform to the same prognosis, there may be a quality of life benefit
principles in PD prescription, taking into account from a modified dialysis prescription to minimize
resources limitation (Fig. 19.7). treatment burden (Table 19.11).
398 A. Y.-M. Wang
Table 19.11 Evaluations in PD patients with a low Kt/V regarded as sufficient ultrafiltration. Values below
or CrCl result
this indicate relative ultrafiltration failure (UFF).
1. Are there incomplete or missed collection of Symptoms of UFF may not manifest overtly until
24 h urine and dialysate?
2. Any non-adherence to the dialysis prescription
RKF has declined significantly or completely
or missed cycles? lost.
3. Any clinical and other biochemical evidence of Ultrafiltration is an important parameter for
inadequate dialysis? assessing adequacy of dialysis, and ultrafiltra-
4. Are the dialysis prescription, namely the number
of cycles and the concentration of PD solutions
tion has been shown to be associated with sur-
optimal for the patient? vival in anuric APD patients; low ultrafiltration
5. Are actual dwell times differ from that volume below 750 ml per day was associated
prescribed? with a higher mortality (176). However, a
6. Any recent loss in residual urine volume and
RKF?
numerical target for daily ultrafiltration volume
7. Any incomplete drain was not recommended as the overall volume
8. Any hypercatabolic conditions? status depends also on the residual urine volume
as well as salt and fluid intake of patients and
there may be substantial intra-individual
valuation of Patients with Low
E variation.
Delivered Urea/Creatinine The ISPD guideline 2020 as well as the ISPD
Clearance Values Cardiovascular and Metabolic guidelines 2015
emphasized the importance of maintaining
eneral Principles in Adjusting PD
G euvolemia as one of the key treatment goals in
Prescription PD. Attention should be paid to both urine vol-
umes and PD ultrafiltration volumes.
If dialysis dose is confirmed inadequate, dialy- Sodium and fluid removal are important pre-
sis dose may be increased by increasing the dictors for survival in PD patients. Fluid overload
instilling volume as tolerated, thereby maximiz- is a highly prevalent complication in PD patients.
ing mass transfer and dwell time or by increas- The estimated prevalence of fluid overload using
ing the number of daily PD exchanges while bioimpedance spectroscopy, was at least over
maximizing the dwell time. For example, for PD 50% in PD patients and was even higher in anuric
patients who are prescribed three daily patients. Patients with fluid overload is associ-
exchanges of 2 L × 1.5% and have a low Kt/V ated with increased risk of mortality.
because of loss of RKF, one may increase the Many factors contribute to fluid overload in
dialysis dose by either increasing to four PD patients, one of which is low drain volume or
exchanges daily of 2 L × 1.5% or by increasing ultrafiltration (Table 19.12). It is essential to take
the volume per exchange to 2.3–2.5 L × 1.5% as a thorough history and physical examination
required and as tolerated. If there is a need to (Fig. 19.8 and Table 19.13).
increase ultrafiltration volume as well, then one
may consider replacing 1.5% with 2.5%
solution. High Transporters
Patients who are high transporters equilibrate

ltrafiltration and Volume Control
U very quickly and have excellent diffusive trans-
as a Treatment Target port capacity. However, a major clinical prob-
lem encountered by high transporters is
Generally, a net ultrafiltration >200 mL from a suboptimal ultrafiltration, low drain volume and
standard 4-hour dwell of 2.27%/2.5% glucose/ inadequate solute clearance as the osmotic gra-
dextrose or > 400 ml from a standard 4-h dwell of dient for glucose dissipates relatively quickly.
3.86%/4.25% glucose/dextrose solution is High transporters would be more suited to do
short dwell times as in APD or NIPD using stan- status is associated with an increased mortality.
dard glucose solution and then a long day dwell Proposed mechanisms for increased mortality
using icodextrin. observed in high transporters include fluid over-
Some patients may start as high transporters load, chronic inflammation, increased peritoneal
but some may gradually become high transport- protein loss and increased risk of PEW.
ers over time on PD. A high peritoneal transport
Table 19.12 Factors contributing to fluid overload in PD Low Transporters

patients
Patient related factors Low transporters ultrafiltrate well but equilibrate
• Adherence to dietary salt and fluid intake slowly. Low transporters may do best with longer
• Compliance to PD regimen
day dwells such as CAPD with a single overnight
• Loss of residual kidney function
• Blood glucose control exchange or CCPD with fewer overnight
• Health literacy exchanges.
• Heart disease and heart failure
• Inflammation
• Protein-energy wasting syndrome
Dialysis related factors cute Peritoneal Membrane
A
• Mechanical factors eg. catheter function, leaks, Dysfunction
hernias, fibrin
• Low ultrafiltration due to
Patients with acute peritonitis may develop acute
– high peritoneal solute transport
– peritoneal membrane failure reduction in drain volume and increased perito-
– constipation neal solute transport. as a result of an increased
– encapsulating peritoneal sclerosis effective surface are and an increased vascular
Fluid overload
Check for causes:-

1. Low drain volume
2. Diet and fluid compliance issues
3. Loss of RKF
4. Dialysate leaks
5. Catheter malposition
6. Non-adherence to PD prescription
Check PET results and RKF

Do a rapid 2L exchange, check drain volume
AXR if catheter malposition suspected
Check if any compliance issues
Check dietary salt and fluid in take pattern
If cause of fluid overload remains unexplained
If drain volume low, then True If drain volume not low, then look for
Loss of Ultrafiltration other causes such as –
non-compliance to dialysis
prescription and to diet, loss of
Review PET D/P Cr ratio residual kidney function
Increased D/P Cr Stable D/P Cr
–Sclerosing peritonitis –Type 1 UFF – lymphatic absorption

–Peritoneal adhesions –Recent peritonitis –Catheter malposition
–Dialysate leaks
–Decreased transcellular transport
D/P Dialysate to plasma, UFF ultrafiltration failure, PET peritoneal equilibration test, RKF residual kidney function
Fig. 19.8 Approach to patients with fluid overload

400 A. Y.-M. Wang
Table 19.13 Clinical evaluation in patient with low The cumulative incidence of UFF was esti-
drain volume
mated to be 2.6% after 1 year on PD, rising to
If drain volume is low, review: 9.5% after 2 years and to 30.9% after 6 years.
(i) any mechanical issues that may explain low
Peritonitis may partly influence the time course
drain volume
(ii) any constipation of small solute and solute-free water transport.
(iii) is outflow position related Patients with previous peritonitis showed an ear-
(iv) catheter position lier and more pronounced increase in the mass
(v) Any fibrin clots that may obstruct outflow transfer area coefficient for creatinine and glu-
(vi) Any omental wrap cose and a decrease in solute-free water transport
(vii) Peritoneal membrane transport characteristics and ultrafiltration rate compared to patients with
(viii) Any features to suggest peritoneal adhesions
or encapsulating peritoneal sclerosis
no peritonitis. In long-term peritonitis-free PD
patients, small solute transport decreased, while
ultrafiltration increased.
permeability. Short term adjustment of PD pre- Type II UFF occurs as a result of loss of peri-
scription may be needed to improve toneal surface area, resulting in decrease in peri-
ultrafiltration. toneal transport of small solutes and water. This
is less common and usually occurs in the context
of peritoneal adhesions secondary to severe peri-
Ultrafiltration Failure (UFF) tonitis or after surgical complications that sub-
stantially reduces peritoneal surface area and
Conventionally, UFF is defined as having a net transport capacity for both solutes and water.
ultrafiltration volume below 400mls with a stan- Type II UFF may be a manifestation of encapsu-
dard 2 L 3.86% glucose solution during a 4 h lating EPS although in early stages of EPS, a high
exchange. rather than a low peritoneal transport is usually
There are 3 types of UFF. Type I UFF is the seen. EPS can be diagnosed by contrast CT
commonest and is partly attributed to long- abdomen.
standing glucose exposure of the peritoneal Type III UFF occurs when lymphatic reab-
membrane. Peritoneal membrane showed sorption of fluid from the peritoneal cavity is
submesothelial fibrosis, vasculopathic changes large enough to reduce ultrafiltration. It is a diag-
and neovascularization. The neovascularization nosis by exclusion since peritoneal lymphatic
increases the effective peritoneal surface area, flow is not measured in most PD centers
leading to more rapid PSTR. The process is (Table 19.14).
thought to be mediated by vascular endothelial To evaluate UFF, a modified PET using 3.86%
growth factor (VEGF) through induction of glucose solution is preferred over 2.5% dextrose
nitric oxide. Clinically, the osmotic gradient for solution to maximize osmotic drive (227). During
glucose dissipates rapidly before adequate ultra- the PET, the D/P sodium curve typically shows
filtration has occurred due to very high PSTR. It an initial fall due to high ultrafiltration rate.
usually has a more gradual onset and increases Ultrafiltration is low in sodium concentration ini-
with time on PD. In some cases, temporary ces- tially due to sodium sieving. Dialysate sodium
sation of PD or resting the peritoneal membrane concentration reduces, resulting in a fall in the
may allow re-mesothelialization and may tran- D/P sodium ratio. With the cessation of ultrafil-
siently improve ultrafiltration capacity (216). tration later in the dwell, dialysate sodium gradu-
However, in some cases, encapsulating perito- ally equilibrates with that of plasma, and D/P
neal sclerosis (EPS) may develop after switch- sodium ratio gradually returns back to baseline.
ing to hemodialysis. Absence of the initial fall in D/P sodium ratio is a
AL GRAWANY
Table 19.14 Summary of Characteristics in the 3 types

of UFF
• In assessing patients suitability for PD
Types Characteristics therapy, it is important to assess patients’
I Patients classically on PD for years, presented medical history, comorbidities, bowel
with a low drain volume, PET showed a high
D/P creatinine ratio. habits, personal hygiene and prior
Attributed to long exposure of peritoneal abdominal surgeries as well as general
membrane to glucose solutions, leading to condition, ability to perform PD, family
submesothelial fibrosis, vasculopathic changes support and home environment.
and neovascularization of the peritoneum and
an increase in the effective peritoneal surface • PD is contraindicated if the peritoneal
area. cavity is obliterated or membrane not
II Patients classically presented with a low drain functional due to peritoneal adhesions.
volume and PET showed a low D/P creatinine • Choice of PD modality should be per-
ratio. Decrease in peritoneal transport of small
solutes and water due to loss of peritoneal
sonalized involving a shared decision-
surface area. Characterized by a decrease in the making approach between physicians
osmotic conductance to glucose and an and patients after patients are educated
attenuation of sodium sieving. on the different modalities.
Usually occurs in the context of peritoneal
adhesions secondary to severe peritonitis,
• PD is possible in both planned and
encapsulating peritonitis or after surgical unplanned and urgent or nonurgent start.
complications. In urgent start PD, patients have limited
III Occurs when there is high lymphatic time to receive education for an
reabsorption of fluid from the peritoneal cavity
informed decision making, these
that reduces ultrafiltration.
patients need to be provided the required
education and support to enable transi-
tion to their preferred modality where
feature of UFF and typically seen in the early feasible.
phase of EPS. • For patients who chose PD modality,
Current treatment for UFF is lacking. For Initiation of therapy should be consid-
Type 1 UFF, a period of peritoneal rest may tran- ered in the presence of symptoms or
siently improve ultrafiltration capacity. For type signs attributable to kidney failure,
II and III, permanent switch to hemodialysis is inability to control volume status or
required. blood pressure and progressive deterio-
ration in nutrition status due to uremic
symptoms.
• In prescribing PD solutions, icodextrin
Practice Points is recommended to improve ultrafiltra-
• Pre-dialysis education involving a mul- tion independent of the dialysate to
tidisciplinary team help patients to bet- plasma creatinine ratio by the 2020
ter understand kidney failure, accept International Society of Peritoneal
dialysis, make their preferred choice of Dialysis (ISPD) Guideline.
dialysis modality and maintain a feeling • Neutral pH, low glucose degradation
of control with their health condition. products solutions is recommended for
Pre-dialysis education has also been better preservation of residual kidney
shown to facilitate patients choosing function if used for 12 months or more
home peritoneal dialysis as the according to the ISPD 2020 and 2015
modality. guidelines.
402 A. Y.-M. Wang
Conclusions
• PD prescription should be ‘goal-
directed’ and should involve shared For the 68 year old lady discussed in the clinical
decision-making in establishing a per- case, peritoneal dialysis offers the advantages of
sonalized realistic care goal that main- being able to undergo kidney replacement ther-
tains quality of life for the person doing apy at home, while enjoying her family life,
PD as much as possible, enables them to maintaining her residual kidney function, fewer
meet their life goals, minimize symp- dietary restrictions, a more gradual correction of
toms and treatment burden while ensur- her metabolic acidosis, whilst avoiding the com-
ing the delivery of high quality care. plications, inconvenience and costs associated
• In order to ensure high quality PD care, with in-centre haemodialysis. She will neverthe-
the following assessments should be less require close monitoring of her peritoneal
included: (1) Patient reported outcome dialysis adequacy and ultrafiltration, and prepa-
measures, (2) volume status, (3) nutri- ration for transplantation.
tion status, (4) uremic solutes removal.
• Preserving residual kidney function
(RKF) is an important treatment strategy Questions
in PD patients as having better preserved
RKF is predictive of better clinical out-
comes. RKF should be monitored at least 1. A 36-year-old man with end stage kidney fail-
once every 6 months in PD patients with ure due focal segmental glomerulosclerosis,
urine output. Management should focus on peritoneal dialysis for six years presented
on preserving it as long as possible. with shortness of breath and leg swelling. He
• Patients who remain symptomatic used 15 L of glucose based peritoneal dialysis
despite a Kt/V > 1.7 should have other fluid with an osmolality of 395 mosmol/L for
dialysis and non-dialysis related factors nighttime daily dialysis for the last few
reviewed as possible contributing fac- months. His ultrafiltration was 300 mL per
tors. This include hypokalemia, protein day. He produced very little urine. On exami-
energy wasting, hypoalbuminemia and nation his blood pressure was 160/80 mmHg
hyperphosphatemia. pulse 90 beats per min respiratory rate 20
• Maintaining euvolemia is one of the key breaths per minute, with leg oedema. His
treatment goals in PD patients and atten- respiratory system exam revealed bibasilar
tion should be paid to both urine vol- crackles.
umes, PD ultrafiltration volumes as well What is most likely cause of his fluid
as salt and fluid intake pattern of retention?
patients. A. Increased plasma hydrostatic pressure
• Patients with low drain volume should B. Decreased plasma hydrostatic pressure
evaluate any mechanical issues, consti- C. Heart failure with preserved ejection
pation, whether drain is position-related, fraction
catheter position, any fibrin clots that D. Low plasma osmotic pressure
may obstruct outflow, any omental E. Lack of osmosis across the peritoneal
wrap, peritoneal membrane function membrane
and any features to suggest peritoneal Answer E Increased glucose concentration is
adhesions or encapsulating peritoneal associated with damage and fibrosis of the
sclerosis. peritoneal membrane
2. A 55-year-old end stage kidney failure patient without any history of diabetes, hypertension
on peritoneal dialysis presented with recur- or heart disease. He was prepared for a perito-
rent abdominal pain fever and cloudy peritoneal catheter placement as PD was his modal-
neal effluent. She was treated for ity of choice. What measures help and
staphylococcal peritonitis a month before. On uncomplicated start of dialysis.
exam she had blood pressure of 130/84 mmHg, A. Erythropoietin therapy before catheter
pulse 84 beats per minute, temperature 36 placement
degrees Celsius. Her abdomen was soft and B. Iron therapy before catheter placement
non-tender. Her peritoneal fluid showed 600 C. Prophylactic antibiotic at catheter
white cells per ml and culture grew Candida placement
albicans. D. A surgical catheter placement as opposed
What is the next best step management? to medical catheter placement
A. Start intraperitoneal vancomycin and E. Prophylactic anticoagulation
intravenous gentamicin Answer C Prophylactic antibiotic is beneficial to
B. Start oral fluconazole prevent infections
C. Start intravenous amphotericin 5. A 56-year-old female with polycystic pre-
D. Start oral fluconazole and remove perito- sented with tiredness and eGFR of 10 mL/
neal dialysis catheter min/1.73 m2. She opted for peritoneal
E. Start intravenous cefuroxime dialysis.
Answer D Fungal infection is an indication for What is not an indication to start dialysis?
catheter removal, difficult to eradicate A. An eGFR of 10 mL/min/1.73 m2
3. A 56-year-old woman with known liver cir- B. Symptoms of nausea, vomiting and
rhosis and ascites due to autoimmune hepati- anorexia
tis and ESKD due to IgA nephropathy was C. Fluid overload not responding to diuretic
referred to advanced CKD clinic. Her eGFR therapy
was 15 ml/min. Physical examination showed D. Recurrent hyperkalaemia
ascites. She opted to have peritoneal dialysis E. Weight loss and poor nutritional status
for her ESKD. Answer A all but an absolute eGFR are indica-
What is true about peritoneal dialysis in tions for starting dialysis
patients with liver cirrhosis?
A. Associated with increased risk of Test your learning and check your understanding
peritonitis of this book’s contents: use the “Springer Nature
B. Associated with increased risk of perito- Flashcards” app to access questions using https://
neal leak sn.pub/cz9Cok. To use the app, please follow the
C. Increased risk of encapsulating peritonitis instructions in Chap. 1.
D. Does not help the drainage of ascites
E. Peritoneal dialysis as a therapy for ESKD
is contraindicated Further Reading
Answer A PD in Cirrhosis patients can be done,
helps drain the ascites but increases risk of Brown EA, Blake PG, Boudville N, Davies S, de Arteaga
J, Dong J, Finkelstein F, Foo M, Hurst H, Johnson DW,
infection Johnson M, Liew A, Moraes T, Perl J, Shroff R,
4. A 55 year-old man with IgA nephropathy pre- Teitelbaum I, Wang AY, Warady B. International
sented in the advanced CKD clinic with an Society for Peritoneal Dialysis practice recommenda-
eGFR of 10 mL/min/1.73 m2, haemoglobin tions: prescribing high-quality goal-directed peritoneal
dialysis. Perit Dial Int. 2020;40(3):244–53. https://doi.
102 g/L and leg oedema. He was slim and org/10.1177/0896860819895364. Epub 2020 Jan 21.
404 A. Y.-M. Wang
Morelle J, Stachowska-Pietka J, Öberg C, Gadola L, La literature and revision of recommendations. Perit Dial
Milia V, Yu Z, Lambie M, Mehrotra R, de Arteaga J, Int. 2020;40(3):254–60. https://doi.
Davies S. ISPD recommendations for the evaluation of org/10.1177/0896860819898307. Epub 2020 Jan 14.
peritoneal membrane dysfunction in adults: classifica- Crabtree JH, Shrestha BM, Chow KM, Figueiredo AE,
tion, measurement, interpretation and rationale for Povlsen JV, Wilkie M, Abdel-Aal A, Cullis B, Goh
intervention. Perit Dial Int. 2021;41(4):352–72. BL, Briggs VR, Brown EA, Dor FJMF. Creating and
https://doi.org/10.1177/0896860820982218. Epub maintaining optimal peritoneal dialysis access in the
2021 Feb 10. adult patient: 2019 update. Perit Dial Int.
Boudville N, de Moraes TP. 2005 Guidelines on targets 2019;39(5):414–36. https://doi.org/10.3747/
for solute and fluid removal in adults being treated pdi.2018.00232. Epub 2019 Apr 26.
with chronic peritoneal dialysis: 2019 update of the
Complications of Peritoneal
Dialysis: Prevention
20
and Management
Brett Cullis and Robert Freercks

A 35 year old male PD patient presents with a
24 h history of nausea, vomiting and generalised Peritoneal dialysis (PD) is a vital form of kidney
abdominal pains. He has end stage kidney dis- replacement therapy, that—once patients (and
ease (ESKD) due to diabetes mellitus, and started their carers), are trained and comfortable with the
dialysing via automated peritoneal dialysis rigorous hygiene involved in catheter care tech-
(APD) six months ago. He has not noted any niques—enables patients to dialyse safely and
problems with drainage; he says that his bags independently at home, often with very limited
have remained clear, and he continues to manage specialist support, for many years. Conversely, PD
ultrafiltration of around 1 L per day, alongside a complications are not uncommon, and can lead to
native urine output of 1 L per day. His most recent significant morbidity and mortality—particularly
PET test, undertaken earlier this month, showed in lower middle income countries (LMIC), where
him to be a high average transporter. His PD the provision of alternative forms of kidney
catheter exit site is clean, and there is no purulent replacement therapy (KRT) is not guaranteed. PD
discharge emanating from this. He is currently complications can be simply divided into infective
apyrexial, is able to lie flat, and has no peripheral (75%) and non-infective causes (25%). Clinicians
pitting oedema. His blood pressure was 124/84, need to be well-versed in prevention, investigation
and his pulse 64 beats per minute. and management of PD complications. In this
chapter, we shall discuss in detail the complica-
tions of PD, and their appropriate management
pathways and strategies for prevention.
Infective Complications
B. Cullis (*)
Hilton Life Renal Unit, Hilton, South Africa Apart from catheter malfunction, infections pose
Department of Nephrology and Child Health, the biggest threat to the continuity of PD in an indi-
University of Cape Town, Cape Town, South Africa vidual, and represent an important barrier to the
R. Freercks uptake of PD. Where there may be no alternative
Department of Nephtrology, Livingstone Hospital, forms of KRT in LMIC, this can lead to significant
Port Elizabeth, South Africa
morbidity and mortality [1]. Clinicians must there-
Department of Nephrology and hypertension, fore be well-versed in the effective prevention and
University of Cape Town, Cape Town, South Africa
https://doi.org/10.1007/978-3-031-09131-5_20
406 B. Cullis and R. Freercks
management of infection in PD, and should develop 5. The use of anti-fungal prophylaxis during
clear protocols in their own units for use by all staff. antibiotic treatment for peritonitis (with
Much progress has been made over the last few nystatin or fluconazole, depending on local
decades in addressing the prevention and treat- resistance and drug interaction concerns).
ment of infections in PD, and in providing sound 6. Soaking of the transfer set adapter in 10% povi-
recommendations for clinical practice. To this end, done iodine solution at transfer set change [6].
the International Society for Peritoneal Dialysis
(ISPD) has published graded and pragmatic guide- Observational data has shown that automated
lines for clinical use which were recently updated peritoneal dialysis (APD) may be associated
in 2016 (peritonitis) and 2017 (catheter-related with a lower risk of peritonitis, but definitive
infection) [2, 3]. We will focus on many of these data is lacking. Other measures that appear to be
recommendation in this chapter, but it is important helpful but lack randomised data include the use
to note that the local context will determine which of prophylactic antibiotics for touch contamina-
problems are prevalent in any specific area and tion or accidental disconnection (gram positive
recommendations will need to be adapted accord- cover) and prior to most endoscopic/dental pro-
ingly. Patients on PD are also at increased risk for cedures (gram positive and negative cover) and
systemic infections such as tuberculosis (TB), and the avoidance of hypokalaemia and constipation
other severe bacterial and viral illnesses, but this to reduce bacterial translocation. Loss of patient
chapter will focus on those specific to PD. motivation and depression are also risk factors
It is recommended that each PD unit monitors for infection and should be actively enquired
the incidence of peritonitis as a quality control after during patient interactions.
indicator. While the overall peritonitis rate should The ideal exit site should be situated away
be less than 0.5 episodes per year at risk, the rate from the belt line and skin folds and be down-
achieved will depend on local factors, including ward and lateral facing to allow for good drain-
whether patients have been given a choice in age. Showering is permissible, as is swimming
terms of dialysis modality, clinic attendance, and in the sea or private pools, however baths and
possibly sociodemographic factors and comor- communal pools should be avoided, and are
bidities such as HIV and diabetes. Lower socio- associated with pseudomonal infections. Many
economic status has not been consistently shown recommend covering the exit site during swim-
to associate with peritonitis risk [4, 5]. ming with an occlusive dressing such as an
stoma bag. Patients should keep their nails
trimmed and inspect and clean the exit site at
Prevention of Infection least twice weekly or after every shower, follow-
ing hand hygiene in a clean environment free of
The key emphasis needs to be placed on adequate wind and pets. The exit site can be cleansed with
training of the patient by experienced staff in soap and water or 2% chlorhexidine or similar
terms of hand hygiene, exit site care and exchange antiseptic. After rinsing and drying the exit site
technique. Further specific measures have also well, a small amount of antibacterial ointment
been shown to be effective: can be applied with a cotton bud or gauze and
then dressed with gauze and secured with tape.
1. The administration of prophylactic antibiotics In warm climates, leaving the exit site open has
(with gram positive cover such as cefazolin or also been shown to be a safe option. Avoidance
vancomycin) prior to catheter insertion. of excessive movement at the exit site is very
2. Daily topical application of mupirocin or gen- important and taping the catheter to the skin
tamicin preparations to the catheter exit site. about 2 cm away from the exit site should be
3. Adequate catheter immobilisation during done. Securing the catheter extension set in a
daily care. purpose-made fabric belt has proven very useful
4. Modern connectology: The use of disconnect in assisting immobilisation. There are currently
systems that utilize a “flush before fill” design no firm data to recommend one dressing or
and avoidance of manual spike systems. cleaning solution over any other.
20 Complications of Peritoneal Dialysis: Prevention and Management 407
Diagnosis of Infection Table 20.2 Exit site scoring systema

Parameter 0 1 2
Effective treatment involves the rapid recognition Swelling No Exit only >0.5 cm and/or
(<0.5 cm) tunnel
of infection in order to preserve PD as a tech-
Crust No <0.5 cm >0.5 cm
nique. Patients should be taught how to recognise
Redness No <0.5 cm >0.5 cm
infection at home to facilitate early presentation Pain No Slight Severe
for assessment. Infections in PD can present as Drainage No Serous Purulentb
either, or a combination of both catheter-related Infection should be assumed with a score of 4 or higher
infection and/or peritonitis: a
Modified from Schaefer F et al.
b
Purulent drainage, even by itself, is sufficient to indicate
infection. A score of less than 4 may or may not represent
Catheter-Related Infections
infection
Exit site infections are often associated with
poor catheter care and subsequent peritonitis and
catheter loss. Scoring systems can be used to
assist with the evaluation of the exit site (see
Table 20.1 Presentations of PD infections Table 20.2). Tunnel infection usually occurs in
Presentations of PD infections association with an exit site infection. Signs of
1. Catheter-related infection inflammation are present along the catheter tun-
(a) Exit site infection—purulent discharge at
catheter exit site with or without erythema; nel tract, although this may be occult, in which
confirmed on culture of exit site specimen. case fluid can be demonstrated ultrasonographi-
Tunnel infection—clinical inflammation or cally around the catheter tract [7]. This distinc-
ultrasonographic evidence of fluid collection along the tion is important, due to the higher risk of
subcutaneous catheter tract.
2. Peritonitis
refractory infection or progression to peritonitis,
(a) Diagnosed in the presence of two of the especially in the presence of Staphylococcus
following three: aureus infection. Any discharge present should
• Generalised abdominal pain with or without be cultured.
other symptoms.
• Cloudy dialysis effluent with a white cell
count >100/μL (0.1 × 109/L) and >50% Peritonitis
polymorphonuclear (after minimum 2 h Peritonitis can be catheter-related through touch
dwell). contamination or through extension of exit site/
• A positive dialysis effluent culture.
(b) For patients on APD, a percentage
tunnel infection into the peritoneal space. It can
neutrophils >50% should be considered also be secondary to translocation of bacteria from
indicative of peritonitis even if the WCC is the gut or though transient bacteraemia, either
<100, due to the short dwell times. spontaneously, after invasive procedures or fol-
Alternatively, a 1 L manual 2 h dwell can be
performed in the unit in order to obtain
lowing a bowel perforation. Peritonitis should be
sample for culture. suspected in the presence of abdominal pain or a
(c) Note the differential diagnosis of cloudy cloudy dialysis effluent and should be promptly
effluent also includes: Chemical peritonitis investigated (Table 20.3). While cloudy dialysate
due to batch contamination or
dihydropyridine calcium channel blockers,
is usually associated with infection, other non-
eosinophilic peritonitis, hemoperitoneum, infectious causes should be considered, especially
chylous effluent, pancreatitis, malignancy in the absence of abdominal pain (see above).
and specimen after a prolonged period when Localised abdominal pain or polymicrobial infec-
PD has been interrupted.
(d) The presence of a lymphocytic pleocytosis
tion should raise the suspicion for surgical causes
should also prompt investigation for TB such as appendicitis and may warrant specific
peritonitis which is not rare in endemic areas, imaging, surgical assessment and the addition of
although it is often initially neutrophilic. anaerobic cover.
Table 20.3 Steps in Investigating for PD peritonitis with systemic antibiotics along with intensified
Steps in investigating for PD peritonitis daily exit site care and careful clinical follow up.
• Dialysate fluid should be drained and inspected The initial empirical antibiotic choice should cover
then sent for an urgent cell count, gram stain and S. Aureus, according to local or known sensitivity
culture prior to initiation of antibiotics.
• Culture yields should be >85%, and are increased patterns but cover for Pseudomonas should be
by placing 5–10 mL directly into aerobic and added where the patient has a history of such an
anaerobic blood culture bottles and through infection. The prescription should be adapted
re-suspended sediment culture after centrifuge of according to culture results as soon as available.
a 50 mL aliquot.
• It is important to liaise with the local Common appropriate initial empiric choices are
microbiology lab in order to increase diagnostic cloxacillin/flucloxacillin or Clindamycin/
yields. Linezolid, depending on local sensitivities. The
• The exit site and tunnel should be carefully duration of treatment should be a minimum of
evaluated for signs of infection and any purulent
discharge cultured. 2 weeks and until the exit site looks normal, but
• The Gram stain is only predictive of the final 3 weeks for associated tunnel infection or pseudo-
organism, or if fungal elements are present. monas. Where pseudomonas is cultured and is sus-
• The presence of gram-negative rods indicates the ceptible, an effective treatment consists of
need for pseudomonal cover if not already in
place. combined oral ciprofloxacin with topical ciproflox-
acin drops and gauze soaks 4 times per day. The
gauze is soaked in a solution made up of 125 ml of
Treatment of Infections vinegar (acetic acid) mixed with 125 ml of sterile
(or cooled boiled) water and 1 teaspoon of salt.
Catheter-Related Infection Resolution of any tunnel infection should be con-
Clinical judgement is required to distinguish bac- firmed by the absence of fluid around the catheter
terial colonisation (positive culture without evi- on follow-up sonography—persistent fluid around
dence of inflammation) from true infection in the catheter would indicate refractory infection.
order to avoid unnecessary antibiotic prescription For refractory/relapsing exit site or tunnel infec-
and the promotion of antimicrobial resistance. tions in the absence of peritonitis, simultaneous
Apart from culturing any exit site discharge, peri- catheter removal and replacement under antibiotic
tonitis should also be ruled out through fluid cover is recommended [8, 9]. In this instance, low
assessment and culture. Mild exit site infection in volume PD (or supine APD) can be used initially to
the absence of tunnel involvement or peritonitis avoid the need for temporary HD. However, cath-
can initially be managed with intensified local eter salvage therapy has been successfully per-
care. The presence of S. Aureus or Pseudomonas formed by shaving off the external cuff and
on initial cultures, or a failure to respond to this re-tunnelling the catheter through a new exit site
regimen within 1 week would indicate the need under ongoing antibiotic cover. This technique may
for systemic antibiotics, even if initially mild. be preferable, particularly in resource-constrained
Chronic exit site inflammation can lead to the for- areas, and allows continued PD immediately.
mation of a pyogenic granuloma, which can fur-
ther become infected. Topical application of silver Peritonitis
nitrate is often successful in this context and any
associated infection should also be treated. Initial Management of Suspected
Concomitant peritonitis or abdominal wall Peritonitis
abscess implies deep cuff involvement and man- Send appropriate cultures and cell count, exam-
dates catheter removal as well as the use of ine the exit site and tunnel carefully and culture
intraperitoneal antibiotics until catheter removal. In any purulent discharge present. Initiate empiric
this instance and depending on residual renal func- broad-spectrum antibiotics (see Table 20.4) while
tion, temporary haemodialysis may be required. awaiting culture and it is an option to add heparin
More severe exit site and/or superficial tunnel 500u/L to the first few exchanges to prevent
infection and any febrile patient should be treated fibrinous catheter occlusion. Approximately 70%
Table 20.4 Commonly used antibiotics and their dosing sidered for IV antibiotics, although most patients
(adapted from ISPD 2016 update [2])
will be able to be treated as outpatients, provided
ONCE they have ready access to transport back, and
DAILY EACH BAG
DOSINGa EQUIVALENT
their pain is not severe. Ancilliary use of antifun-
(per (mg/L, unless gal prophylaxis (nystatin orally or fluconazole
exchange, indicated 200 mg po alternate days) should be given. Note
DRUG once dly) otherwise) that a temporary increase in dialysate glucose
Vancomycin 20–30 mg/ LD 30 mg/kg,
concentration or use of icodextrin may also be
kg every MD 1.5 mg/kg/
5–7 days or bag necessary since an increase in membrane trans-
if level <15 port due to inflammation is common in peritoni-
Teicoplanin 15 mg/kg LD400 mg/bag/ tis, and may result in fluid overload.
every MD 20 mg/bag
5 days
Basic principles of Antibiotic Therapy for
Cefazolin 15–20 mg/ LD 500/MD 125
kg Peritonitis:
Cloxacillin ND LD 500/MD 125 • Broad spectrum antibiotics to cover both gram
Clindamycin ND MD 600 mg/bag positive and gram negative organisms are ini-
Ampicillin 2 g BD MD 125 tiated empirically but narrowed down after
Ceftazidime 3 g stat, LD 500/MD 125 positive culture is obtained. The combination
then
1–1.5 g/day of a glycopeptide and ceftazidime has been
Ceftriaxone 2 g stat, ND shown to be superior to other regimens [10].
then 1 g/ Glycopeptides cover many inherently
day penicillin-
resistant gram positive organisms
Cefipime 1g LD 500/MD 125 and ceftazidime affords pseudomonal in addi-
Ciprofloxacin ND (can MD 50
use orally) tion to other gram negatives. There are many
Gentamycin 0.6 mg/kg LD 8/MD 4 rational combinations and the choice should
Tobramycin 0.6 mg/kg LD 3 mg/kg/MD be tailored according to local susceptibility
0.3 mg/kg data and ecology (Table 20.4).
Amikacin 2 mg/kg LD 25/MD 12 • Intraperitoneal (IP) antibiotics are superior in
Cotrimoxazole 960 mg orally BD
efficacy compared to IV, with the exception
Fluconazole 200 mg ND
Meropenem 1g LD250/MD125 being in the presence of systemic sepsis. They
Imipenem/Cilastatin 1 g BD LD250/MD50 should be added to the dialysate in a sterile
Note: Most antibiotics are stable for at least 5 days when fashion (after 5 min of disinfection of the
mixed in the bag and stored at room temperature. The injection port) by trained personnel.
exception to this is ampicillin (12 h) where intermittent • Once-daily IP treatment of most antibiotics is
mixing/dosing required. (At room temperature: possible and has equivalent efficacy to inter-
Vancomycin is stable 28 days, Gentamycin 14 days,
cefazolin 8 days; Ceftazidime 4 days, but 7 days if refrig- mittent dosing, provided the dwell is at least
erated). First line agents are all stable in icodextrin if 6 h.
refrigerated • Antibiotics can be added to the same bag but
a
Once daily dosing requires a dwell of at least 6 h should not be mixed in the same syringe.
LD = loading dose per litre in first bag, MD = mainta-
nence dose per litre in each bag, ND = No data • Antibiotics can be mixed in the unit and pro-
vided to patients to take home with them.
They can be mixed at home, but given the sta-
of infections are related to gram positive organ- bility of the agents, in-unit mixing is
isms, with the balance being gram negative or preferable.
other (such as fungal or mycobacterial). Consider • Serum vancomycin levels can be checked
whether a surgical cause for peritonitis may be after 3–5 days, and a trough concentration of
present and manage appropriately. Patients who >15 μg/ml should be maintained, although
have systemic sepsis should be admitted and con- there is no good evidence to support this prac-
tice. Dosing is usually required every 7 days, (Table 20.5). Cure rates for fungal peritonitis
but every 3–5 days in those with good residual are less than 10%.
kidney function. • Early catheter removal is mandatory for all
• Aminoglycosides appear largely safe when organisms if there is concomitant tunnel infec-
necessary and do not impact residual kidney tion (or where an exit site organism is the
function or cause ototoxicity when dosed cor- same as peritoneal fluid), with the exception
rectly, daily and for ≤1 week. However, where for coagulase negative staphylococcal (CNS)
an alternative non-toxic therapy is unavailable, and streptococcal infection that is rapidly
safe use has been reported over up to 3 weeks. responding (Table 20.5).
• Data concerning APD are scant, but strategies
for dosing include dosing per bag as for CAPD Specific Organisms and Their Treatment
(preferred strategy), reprogramming the cycler In general, the narrowest spectrum antibiotic avail-
to allow a daily 6-hour dwell, switching to able should be used to limit the development of
CAPD for the duration of treatment, and inter- resistance. Some specific recommendations can be
mittent instillation of a 6-hour dwell for gly- made regarding certain organisms (Table 20.6):
copeptide dosing [11].
Final Assessment of the Patient:
• The duration of therapy should be 3 weeks,
Further Assessment of the Patient Should but 2 weeks in CNS/streptococcal infection
Occur Within 2–3 Days: with a rapid response.
• Most patients improve rapidly within 2–3 days • After catheter removal, treatment should con-
and failure to do so demands re-consideration tinue for 10–14 days.
of the diagnosis, possible further imaging • Each peritonitis episode should be interro-
(Chest radiograph/CT Abdomen/ultrasonog- gated and patients should be re-trained
raphy of the tunnel), repeat cell count/cultures regarding hygiene and aseptic technique plus
including TB/fungal cultures and a possible touch contamination protocols.
switch in therapy to broaden cover. Failure to • The transfer set should be changed once fluid
respond by day 5 necessitates prompt catheter clears.
removal to protect the membrane. A high
index of suspicion for TB should also be
maintained in endemic areas. Table 20.5 Indications for PD catheter removal
• Dialysate cell count >1090 cells/μL
Catheter removal is considered necessary for:
(1.09 × 109/L) on day 3 strongly predicts treat- 1. Refractory peritonitis (failure to resolve by day
ment failure [12]. 5).
• For patients that have responded well clini- 2. Fungal peritonitis
cally, antibiotic therapy should be narrowed 3. Relapsing peritonitis (peritonitis with same
organism ≤4 weeks after successful treatment)
according to culture results. 4. Refractory exit site or tunnel infection.
• For those patients with a rapid clinical Note: For relapsing peritonitis due to non-virulent organ-
response but negative culture, it is usually safe isms or in the presence of persistent exit site/tunnel infec-
to continue only gram positive cover provided tion with resolved peritonitis, simultaneous removal and
the cell count has dropped markedly by day 3, replacement of the catheter can be safely performed after
2–3 week’s treatment, sometimes avoiding HD. However,
since most culture negative episodes are gram for refractory peritonitis, a new catheter should only be
positive in origin. An alternative is to continue placed a minimum of two weeks after full resolution of
an oral quinolone antibiotic for 10 days. peritonitis. Successful return to peritoneal dialysis after
• The presence of fungal elements on initial catheter removal for infection is successful in a large
number of patients, but should be carefully considered in
gram stain or subsequent culture demands those with repeated infections (peritonitis with a different
immediate removal of the catheter and a organism ≥4 weeks after successful treatment) or after
switch to include antifungal treatment fungal peritonitis
Table 20.6 Specific recommendations for management Prognosis

of PD peritonitis due to isolated organisms
Organism Management Most patients recover rapidly, but the risk of
Coagulase • Where methicillin sensitive, requiring catheter removal is approximately
negative continuous instead of daily
Staphylococci treatment with first 20%. The overall mortality rate is approximately
(CNS) generation cephalosporins is 5% but is highest for those with fungal, gram
preferred. negative, S. aureus or TB infections. While the
Staphylococcus • High risk for catheter reasons are poorly understood, a recent episode
aureus removal.
• Where methicillin sensitive,
of peritonitis is also associated with an increased
first generation odds of all-cause death for the next few months,
cephalosporins are but especially in the first 30 days. Other possible
preferred. consequences of peritonitis include the forma-
• A nasal swab for S. aureus
should be performed, and
tion of infected intra-abdominal collections,
where positive, eradication fibrous adhesions and encapsulating peritoneal
measures should be sclerosis.
attempted.
Pseudomonas • High risk for catheter
removal.
• Two antibiotics with Non-Infective Complications
different mechanisms of
action should be used (also Approximately 25% of cases of technique fail-
for Stenotrophomonas): Oral
ure in PD occurs as a result of some form of
ciprofloxacin can be
combined successfully, but mechanical complication. These can involve the
must be dosed apart from catheter itself with poor drainage or alternatively
phosphate binders, as these the boundaries of the peritoneal space leading to
can bind ciprofloxacin in the
hernias or leaks. The vast majority of these com-
gut, and markedly reduce its
absorption. plications can be dealt with and patients can
• Consider extending return to PD shortly thereafter. This section will
treatment to 28 days in some address these issues and how to prevent and
cases.
manage them.
Enterococcus • Vancomycin is the preferred
species agent where sensitive.
Other • Due regard should be given
enterobacteriaceae to increasing antibiotic PD Catheter Obstruction
resistance and the use of two
agents should be considered
for those organisms with
There are several possible causes of PD catheter
inducible beta lactamase flow complications, as listed in Table 20.7.
inhibition.
• Consultation with
microbiologists is
recommended where Table 20.7 Causes of PD catheter obstruction & Specific
possible. treatments
Tuberculosis • There is a neutrophilic Cause of PD catheter
effluent in 75% of cases. obstruction Treatment
Standard anti-TB therapy is Catheter obstruction Intraluminal tissue
used, and catheter removal is due to fibrin plasminogen activator (tPA)
often not necessary. Catheter migration out Guidewire manipulation of
• Some patients may develop of the pelvis PD catheter
a protein-losing state via
Catheter entrapment in Laparoscopic replacement
their dialysate, which may
the omentum and omentopexy
necessitate a transfer to
HD. Severe constipation Oral bowel preparation
solution
As the PD fluid drains into the true pelvis in omentopexy and tip suturing have been shown in
the upright position, a catheter sited there is much a large meta-analysis to lead to better long term
more likely to drain effectively and to near com- outcomes, with fewer mechanical complications.
pletion. If the catheter has moved out of the pel- As constipation is by far the most common
vis it often (but not universally) leads to poor reason for catheter migration, maintenance of a
drainage. The migration of the catheter may be regular bowel habit through the regular use of
because of significant constipation with the laxatives in PD patients is recommended to pre-
loaded sigmoid colon moving the catheter into vent catheter migration.
the upper abdomen and this is by far the most
common cause. It is easily diagnosed with a plain
abdominal x-ray which shows both the catheter Table 20.8 Advanced laparoscopic techniques to pre-
vent PD catheter blockage
migration as well as the faecal loading. The
Laparoscopic
catheter may also migrate when the omentum
technique Description
wraps around the catheter and with traction pulls Musculofascial • Involves the formation of a
it out of the pelvis. Omental wrapping cannot be tunnelling tunnel along the posterior
distinguished from other causes of migration rectus sheath in a caudal
without the use of laparoscopy. Catheters may direction prior to the catheter
entering the peritoneal space.
also become blocked with fibrin. This usually • Keeps the catheter directed
leads to problems with both drainage into and out into the pelvis, and if
of the abdomen, but occasionally a ball valve migration occurs will allow it
effect may be seen and only inflow drainage to return to its original
position through its elastic
occurs. In this situation, the abdominal x-ray usu- memory.
ally shows the catheter in the correct position. Omentectomy • Was used historically, and can
Some rarer causes of obstruction are reported in be performed via either
the literature, such as obstruction due to fallopian laparotomy or laparoscopic
approaches.
tubes, appendices and other mobile structures in
• Removal of a large proportion
the abdomen. It is also relatively common for of the omentum prevents it
patients with significant peritonitis or following reaching into the pelvis and
surgery to develop adhesions, and these can oblit- entrapping the catheter:
Unfortunately, the omentum
erate the pelvis or create pockets where fluid col-
is a highly vascular structure,
lects and drains slowly. All of the above need to and extreme care needs to be
be diagnosed at laparoscopy or laparotomy. taken to ensure haemostasis
as post-operative bleeding
results in both fibrin
occlusion of the catheter, as
revention of PD Catheter
P well as formation of
Obstruction adhesions.
Omentopexy • Is preferred over
In recently published ISPD access guidelines, omentectomy.
• Involves suturing the end of
practical methods to ensure optimal PD access the omentum to either the
and reduced complications are discussed mesocolon or a point on the
(Table 20.8) [13]. These guidelines analyse meth- anterior abdominal wall in
ods of insertion of catheters, as well as some one of the upper quadrants.
Only needs to be performed
techniques to prevent complications. Although when the omentum is long
there is no evidence of superiority of different enough to reach the level of
methods of insertion of PD catheters in the hands the pelvic brim, and can be
of a skilled operator, if the laparoscopic route is confirmed at the time of
surgery.
chosen, then advanced laparoscopic techniques
such as musculofascial tunnelling, omentectomy,
Table 20.8 (continued) bowel preparation for colonoscopy (e.g. sodium

Laparoscopic picosulphate or macrogol). The patient takes the
technique Description preparation and waits until the bowel has emptied
Tip suturing • Is a controversial technique, significantly before performing the next dialysis
as it can be argued that having
a foreign object may be a exchange.
nidus for infection, and if the Catheter migration without constipation:
catheter is immobilised too Occasionally the catheter will not move into the
tightly it may result in rectal
pelvis of its own accord. This could be due to
or vaginal pain.
• Significantly reduces the omental wrapping in which case it is unlikely to
incidence of catheter move without surgical intervention, however it
migration. may simply be that it is in the incorrect position
• Various techniques have been and a much less invasive method may be used
described from a propylene
loop of suture protruding to manipulate the catheter to get it into position.
from the lower third of the This involves fluoroscopy, and use of a flexible
anterior abdominal wall into guidewire. There are numerous published tech-
the abdominal cavity through
niques, ranging from a stiff wire bent into a
which the catheter travels, to
a loop on the dome of the 270° arc, to various guidewires and angiogra-
bladder, directing the catheter phy catheters, which are advanced under fluo-
into the retrovesical space: roscopic guidance in order to manipulate the tip
Both of these techniques
of the catheter back into the pelvis. The most
allow easy removal of the
catheter if necessary, since the commonly used method uses a relatively stiff
catheter slides through the angiography guidewire with a flexible or
loop unimpeded. j-shaped tip, which is advanced through the
Alternatively, the catheter can
catheter and beyond. As the wire is advanced
be fixed using sutures to the
pelvic sidewall. through the tip, it presses against the abdominal
Note: These techniques cannot be performed if the cathe- side wall and the catheter is pushed downward
ter is inserted percutaneously, however it should be noted into the pelvis. Results from most of the pub-
that although these methods reduce mechanical complica- lished studies show a technique success rate of
tions, many studies show percutaneously inserted cathe- approximately 80%, however publication bias
ters have patency in excess of 80% at one year despite
this, and therefore if using this approach the above laparo- may overestimate the success rate achieved in
scopic techniques can be performed later if a catheter does clinical practice. It is a very low risk, minimally
become problematic invasive procedure though, and if facilities
exist, may prevent the need for surgery and
should be considered [14, 15].
Obstruction of the catheter due to fibrin can be It is imperative that the technique is performed
prevented by the addition of heparin 500-1000iu/l in a sterile manner, and a dose of intraperitoneal
to the PD solution when PD fluid is bloodstained antibiotic is administered as per the unit protocol
or has significant amounts of fibrin present. for catheter contamination episodes, in order to
prevent PD peritonitis.
Should the above not prove successful, then
anagement of PD Catheter
M repositioning of the catheter should be performed
Obstruction surgically. It is preferable to reposition using lap-
aroscopy, as it allows for the above advanced
Catheter migration with constipation: This is techniques to prevent further complications, but
diagnosed by plain abdominal x-ray showing fae- also allows direct visualisation of the catheter,
cal loading with or without migration of the cath- division of adhesions, and placement of the cath-
eter. In the vast majority of cases, this can be eter back in the pelvis under direct vision. Finally,
remedied with a single dose of a solution used for the smaller incisions associated with laparoscopy
than for open laparotomy may facilitate a return tions, which makes defects in the abdominal wall
to PD immediately, provided that the laparo- more apparent. Other factors such as malnutri-
scopic port sites are sutured internally. tion, polycystic kidney disease and surgery for
Laparoscopy is not available in many centres catheter placement also increase the risk. They
due to a lack of expertise, and expensive consum- may become apparent initially, with initiation of
able devices. In this situation, the catheter can be dialysis or after many years. Hernias are defects
replaced by performing a mini-laparotomy, or in the abdominal with an intact peritoneum,
alternatively, the catheter can be replaced at the whereas a leak is a defect where the peritoneal
bedside. This latter technique involves dissection membrane has been disrupted. The latter can
and freeing of the deep cuff under local anaesthe- commonly occur after an episode of peritonitis or
sia. The catheter is slowly withdrawn until the surgery, and with rest may resolve, however her-
first side hole is visualised. Using a peel-away nias almost always need to be repaired.
sheath PD catheter insertion kit, the guidewire is
fed through the side-hole into the abdomen. The Hernias
catheter can then be completely withdrawn, leav- The most common sites for hernias in PD patients
ing the guidewire with the distal tip in the perito- are inguinal, umbilical and paraumbilical. Other
neal cavity. The catheter can be freed of any hernias occurring less commonly are femoral,
fibrin, and then is replaced in the abdomen using diaphragmatic and Spigelian, along with recto/
the peel-away sheath percutaneous technique, vaginocoeles. The usual presentation is a sudden
over the guidewire. swelling over the affected area, however there are
Catheter obstruction secondary to fibrin depo- reports of patients presenting with recurrent peri-
sition: It is common for fibrin to be found in the tonitis associated with intermittent subacute
PD effluent, and this can cause occlusion of the obstruction of bowel.
lumen and side-holes. This can cause both uni- If it is uncertain as to whether there is a hernia
and bi-directional flow obstruction. Under sterile or not, then further imaging may be helpful. The
conditions, the catheter can be flushed vigorously simplest is CT peritoneography (Fig. 20.1).
with saline or PD solution, using a 20 ml syringe. Magnetic resonance imaging (MRI) may also be
Avoid aspirating rapidly, as it is possible to entrap used, with the PD solution acting as the contrast
mobile structures, such as omental folds in the tip media (Gadolinium is usually avoided due to the
of the catheter. Gentle aspiration may alterna- risk of nephrogenic systemic fibrosis and possi-
tively result in removal of the responsible fibrin ble peritoneal fibrosis). This technique may be
plug, and restore PD fluid flow. If this is unsuc- more helpful for diagnosing a leak as discussed
cessful, then the catheter may be locked with a later [16].
thrombolytic solution. The most commonly rec-
ommended is tissue plasminogen Activator (tPA), ernia Prevention and Management
H
which is made up to a 1 mg/mL solution and Prior to insertion of a PD catheter, all patients
8 mls (in an adult Tenckhoff catheter) is slowly should have all potential hernia sites inspected; if
injected and left for 1 h, then aspirated. This will a hernia is present, this needs to be repaired at the
usually result in restoration of flow if fibrin is the time of surgery to place the PD catheter.
cause of the obstruction. If a hernia is diagnosed at a later point, it is
usually advisable for the hernia to be repaired,
but occasionally if it is small, not increasing in
Hernia and Leak size, and has a wide neck, it can be left in patients
who have a limited life expectancy. In other
Hernias and leaks occur in approximately 15% of patients, due to the likelihood of significant wors-
patients on PD, and appear to be more prevalent ening, it should be repaired. Inguinal hernias can
than the general population due to the increased often be repaired using an extraperitoneal
abdominal pressure associated with PD solu- approach which will allow early reinstatement of
Fig. 20.1 CT Peritoneogram demonstrating an inguinal

hernia in a patient who presented with recurrent peritoni- Fig. 20.2 CT peritoneogram demonstrating an extraperi-
tis of unknown cause. Notes: 2 mL/kg of intravenous con- toneal leak into the subcutaneous tissues of the left ante-
trast is injected into a 2 L dialysate bag and instilled into rior abdominal wall
the abdomen. The patient is asked to perform manoeuvres,
which increase the intra-abdominal pressure, such as
coughing, bending and squatting. 30 min after installa- be distinguished from a leak as discussed below.
tion, a standard CT scan of the abdomen is performed, When this is noted unilaterally, there is a signifi-
then the fluid is drained out cant risk of a contralateral leak, such that a bilat-
eral repair should be performed.
PD (see below), however umbilical and paraum-
bilical hernias usually require a procedure which Leaks
breaches the peritoneum, and requires a period of Leaks may occur at any point where there is a
rest from PD. defect in the peritoneal membrane, with the most
Repair of hernias almost always require the common sites being along the PD catheter tunnel
use of a synthetic mesh to prevent recurrence. and trans-diaphragmatic, however numerous
There is debate as to whether this should be other potential sites may occur, including peri-
placed intra- or extra-peritoneally. Intraperitoneal cardial, transvaginal and retroperitoneal.
mesh has the risk of being infected if the patient Figure 20.2 shows a leak in the left flank, which
develops peritonitis in the 2–4 weeks following would occur after heavy exercise. Identification
repair, however there is little evidence of this of a leak may be more difficult than a hernia, as it
occurring in the literature. Until further evidence may be subtle. Features which should alert one to
comes to light, if there is the surgical expertise a leak is poor ultrafiltration in the early phase
available, the extraperitoneal approach should be after starting PD, abdominal wall oedema, with a
considered. peau d’orange appearance, genital oedema, and
Although there is little evidence as to the opti- in the case of a transdiaphragmatic leak, short-
mal timing for reinitiating PD, if the patient can ness of breath. Hydrothorax and transdiaphrag-
delay dialysis then 4 weeks is recommended, matic leaks will be discussed separately.
however if the peritoneum is not breached then If there is poor ultrafiltration due to leakage
10 days is the minimum before resumption of into the soft tissues, this can be identified by per-
ambulatory PD. If the patient is on automated PD forming a peritoneal equilibration test (PET)
(APD), a low volume fill program (1–1.5 L) may which should be discordant with the clinical
be used, with a dry abdomen when ambulating, in picture. If a patient has ultrafiltration failure

order to allow an immediate return to PD, with- (<200 mL with a 2.5% glucose solution) but is a
out the need for bridging HD. low, low average or even high average trans-
A patent processus vaginalis is where there is porter, one should consider a leak and proceed to
a potential connection between the abdominal imaging. There are 3 modalities which are help-
cavity and the scrotum. This often presents as a ful: the first is nuclear scintigraphy, where 2 mCi
unilateral or bilateral scrotal swelling, and must of Technetium radionuclide is added to a 2 L PD
bag. This may identify a leak, but does not give dire consequences for the patient, and requires
good definition. CT or MR peritoneography, as early identification. Significant thickening of the
discussed earlier, may offer better definition and peritoneal membrane results in adhesion of bowel
demonstration of the site of the leak, and where a loops, and cocooning of the bowel, resulting in
repair is needed (Fig. 20.2). bowel obstruction (Table 20.9). There is often
Most leaks may resolve if PD is withheld for a associated ascites associated with this, especially
period of 2 weeks, allowing the peritoneum to in patients who have transferred to haemodialysis
seal itself. If following this rest period, the leak or had a kidney transplant.
recurs, then it will usually require surgical repair. The most common clinical features are vomit-
ing and abdominal pain, with rarer symptoms
Hydrothorax being ascites, blood stained dialysate and an
Hydrothorax occurs due to leakage through a abdominal mass.
defect in the peritoneum and diaphragm. This The cause remains uncertain, with numerous
may be a congenital defect, or alternatively a rup- theories under investigation. One prevalent the-
ture of a pleural bleb. The usual presentation is an ory is that there is a predisposition to membrane
asymptomatic pleural effusion on chest radio- thickening such as increased time on PD, or an as
graph (CXR), however it may cause shortness of yet unidentified genetic cause, following which a
breath and in extremely rare cases, tension hydro- second insult leads to excessive peritoneal mem-
thorax. As with other PD leaks, there is frequently brane fibrosis: this could be an environmental
associated poor ultrafiltration, and the patient toxin, or infection. Underlying this theory is a
may present with oedema and signs of fluid over- strong association with time on dialysis, with
load. It may therefore be difficult to distinguish more than 90% of cases presenting after 3 years
between a pleural effusion secondary to a leak on PD. Although it was initially considered
and one due to fluid overload, or right ventricular important, there is no clear link between number
failure on clinical grounds. A confident diagnosis of peritonitis episodes and the development of
may be made by measuring the glucose in the EPS. Many studies have demonstrated a discon-
fluid aspirated from the pleural space is nect between ultrafiltration failure (UFF) and
>40 mmol/L or >3 mmol/L above that of the peritoneal transporter status: normally, patients
serum. CT/MR Peritoneography or scintigraphy with UFF are high transporters, whereas this is
may also be helpful in diagnosing a leak, and the not necessarily the case in EPS, presumably due
former may even demonstrate the exact position to the fibrotic thickening disrupting the usual per-
which can be sutured thoracoscopically. formance of the membrane in the PET test. This
is important, as many studies have shown that
Management of Hydrothorax patients continuing PD for 3 years or more after
This is determined by whether the leak occurred the development of ultrafiltration failure are at
following an episode of peritonitis or not. If so, exceptionally high risk of EPS.
then following a period of 2 weeks’ rest, the
healed mesothelium may prevent further leakage.
Table 20.9 Clinical and Radiological features of
If it occurs at the start of PD, it is unlikely to Encapsulating Peritoneal Sclerosis (EPS)
resolve spontaneously. The options are then to
Radiological findings on
perform a thoracoscopic surgical repair, or more Clinical presentation CT
commonly pleurodesis. This will usually result in • Typically after • Thickened bowel loops
a good functional outcome, and very seldom >3 years on PD and peritoneum
recurs. • Vomiting • Diffuse peritoneal
• Abdominal pain membrane calcification
• Ascites • Loculated ascites
Encapsulating Peritoneal Sclerosis (EPS) • Blood stained
Encapsulating peritoneal sclerosis is a condition dialysate
that occurs in 1–2.5% of patients on PD, can have • Abdominal mass
The diagnosis of EPS is usually made with tion, a hernia or fluid leak all less likely causes of
radiological imaging, on the background of the his presentation. Further, the fact that he is a rela-
appropriate clinical picture. The gold standard tively new starter on APD makes EPS improba-
diagnostic test is CT imaging, demonstrating fea- ble. The absence of a purulent discharge from
tures of thickened bowel loops and peritoneum, around his catheter is only part reassuring—from
diffuse calcification of the membrane, and locu- the perspective of helping to exclude an exit site
lated ascites. None of these features is diagnostic. infection. However, as in 75% of cases, the most
Normally in the supine patient, bowel loops tend likely cause of his presentation remains
to “float” on the ascites, and are in contact with PD-associated infection, and we must therefore
the anterior abdominal wall. In patients with pay careful attention to excluding PD peritonitis,
EPS, the bowel loops are often posterior to the for which shorter dwell times associated with
ascites which collects anterior to them. APD may explain his clear bags: sending an
Ultrasound can be used to look for bowel wall urgent PD fluid cell count, gram stain and culture
thickening, but is very operator dependant, and prior to initiation of antibiotics is essential, as per
therefore less reliable for making the diagnosis. the local PD peritonitis protocol, ensuring at least
The optimal therapy for EPS remains uncer- a 6 h dwell time, and with a view to revising anti-
tain. If patients are young, with a reasonable biotics according to the results of the gram stain
prognosis, then a transfer to haemodialysis is rec- and culture.
ommended. Small case series have suggested In conclusion, infectious and non-infectious
some benefit with the use of tamoxifen, cortico- complications of PD are common: Through rig-
steroids and other immunosuppressants. No ran- orous patient training and ensuring familiarity
domised controlled trials have been done to amongst clinicians of local protocols, we can
determine the best treatment, and publication facilitate timely and pro-active investigation and
bias makes it difficult to determine the best management of PD complications, and in the
option. Also, as EPS has different phases from majority of cases, allow patients to return to PD
early inflammatory phase to late fibrotic phase, it for long term dialysis.
may be important to target different therapies at
different stages. Once the patient has developed
symptoms of bowel obstruction, surgical inter- Questions
vention may be necessary. It is recommended
that this be undertaken in a centre experienced
with performing peritonectomy, where a multi- 1. Which of the following are most important in
disciplinary approach to parenteral nutrition, and a patient presenting with cloudy effluent?
a combination of peritonectomy and plication of A. Peritoneal fluid culture and cell count
the intestine can be performed. EPS has a high B. Exit site inspection and pus swab if
mortality, and malnutrition is thought to play a inflamed
key role in this, hence the need for aggressively C. Start on intraperitoneal antibiotics with
treating this prior to surgery. both gram positive and gram negative
cover
D. Discussion on the possible causes for
Conclusions peritonitis and consider retraining the
patient
Returning to our 35 year old PD patient, who pre- E. All of the above
sented in the initial clinical scenario with nausea, Answer: E.
vomiting and generalised abdominal pain: with PD peritonitis is usually simply a coagu-
good drainage of his PD fluid, preserved ultrafil- lase negative staphylococcal infection which
tration, and physical signs consistent with is easily treated, however if appropriate
euvolaemia, we may consider catheter obstruc- investigation of the cause and rapid initiation
of antibiotics to cover gram negative organ- D. A PD effluent cell count >1000 on day 3
isms is not performed then there is a higher is predictive of failure to clear by day 5
chance of catheter loss in those with other E. In relapsing (same organism within
causes. 4 weeks) peritonitis simultaneous
2. The ISPD guidelines recommend a culture removal and replacement of the PD cath-
negative rate of <20% for peritonitis. Which eter after 2 weeks antbiotics is feasible
methods can be used to increase this yield? Answer: C.
A. Centrifuge 50mls of fluid, resuspend the Fungal peritonitis carries a very high
pellet and culture treatment failure rate and a 25% mortality.
B. Inoculate blood culture bottles with Although there are case reports of successful
10mls of PD fluid treatment with antifungals but this is not
C. Ensure fluid samples are collected before recommended.
antibiotics are added to the bag 5. A patient presents with a case of PD peritoni-
D. Discuss with local microbiology lab the tis secondary to pseudomonas aeriginosa, the
importance of the primary samples following are the most appropriate treatment
E. All of the above options:
Answer: E. A. Remove the PD catheter immediately
Discsussion with local microbiologists B. Continue ceftazidime/gentamicin for
can be extremely helpful as peritoneal fluid 2 weeks
specimens are often not regarded as particu- C. Treat with 2 anti-pseudomonal antibiot-
larly important in the lab and may not be ics for 3 weeks
given appropriate consideration. D. Shave the cuff on the catheter as it is the
Understanding of the value of centrifugation most likely source.
and use of blood culture bottles to increase Answer: C.
yield and peritonitis outcomes are essential. Gram negative peritonitis requires 2
3. Exit site infections should be managed with: agents to improve treatment success.
A. Warm compresses with a towel soaked in Although an exit site infection and peritonitis
boiling water with pseudomonas with likely require tube
B. Increased exit site care if mild removal it is not necessary unless refractory
C. Shaving of the cuff and retunneling peritonitis or recurrent peritonitis occur.
D. Antibiotics appropriate to cultures for 6. A patient who has poor ultrafiltration, with a
2 weeks PET test result showing slow average trans-
E. B and D porter status should be considered to have a
Answer E. mechanical complication until proven
Exit site infections may be very mild and otherwise.
immobilisation of the catheter and increased A. True
exit site care can resolve it. If there is a puru- B. False
lent discharge or pain though then appropri- Answer: A.
ate antibiotics are necessary and should be Patients with poor ultrafiltration espe-
continued for 2 weeks cially early in the course of PD and not asso-
4. Which of the following is incorrect? ciated with hyperglycaemia are likely to have
A. Peritonitis which does not resolve by day a mechanical complication, most especially a
5 is called refractory peritonitis leak and CT peritoneography should be
B. If PD effluent has not cleared by day 5 considered.
the catheter should be removed to pre- 7. A patient presents with a right sided pleural
serve the membrane for future use effusion. Which of the following are not
C. Fungal peritonitis can be safely treated likely to assist in the diagnosis of a leak:
with fluconazole but if not cleared by day A. Pleural aspiration showing a fluid:serum
5 then the catheter should be removed gradient >3 mmol/L
B. Echocardiogram to exclude right heart PKD patients often do well on PD and although
failure those with massively enlarged kidneys may
C. Pleural biopsy find large fill volumes uncomfortable, it is not
D. Nuclear scintigraphy a contraindication to therapy. Hernias are
E. MRI of the thorax more common in these patients, and should be
Answer: C. sought and repaired pro-actively, before or at
All of the investigations are helpful in dis- the time of PD catheter placement.
tinguishing between a pleural effusion due to
fluid overload and a leak except c. A pleural Test your learning and check your understand-
biopsy may be necessary in the case of an ing of this book’s contents: use the “Springer
exudative effusion but hydrothorax is always Nature Flashcards” app to access questions
a transudate. using https://sn.pub/cz9Cok. To use the app,
8. Encapsulating peritoneal sclerosis (EPS) is a please follow the instructions in Chap. 1.
rare complication of PD associated with
thickening and cocooning of the peritoneal
membrane. The following are options for References
therapy except:
A. Tamoxifen 1. Boudville N, et al. Recent peritonitis associates with
mortality among patients treated with peritoneal dial-
B. Peritonectomy ysis. J Am Soc Nephrol. 2012;23(8):1398–405.
C. Prednisone 2. Li PK-T, et al. ISPD peritonitis recommendations:
D. Intraperitoneal antibiotics 2016 update on prevention and treatment. Perit Dial
E. Sirolimus Int. 2016;36(5):481–508.
3. Szeto C-C, et al. ISPD catheter-related infection
Answer: D. recommendations: 2017 update. Perit Dial Int.
Although all of the above are treatment options, 2017;37(2):141–54.
there is no consensus on the optimal treatment 4. Davidson B, et al. Outcomes and challenges of a
regimen and randomised trials are needed, PD-first program, a south-African perspective. Perit
Dial Int. 2018;38(3):179–86.
however given the paucity of cases it is 5. Htay H, et al. Center effects and peritoneal dialysis
unlikely this will be achievable. peritonitis outcomes: analysis of a national registry.
9. Rapid of inflow of fluid and poor drainage Am J Kidney Dis. 2018;71(6):814–21.
thereof is likely to be secondary to: 6. Firanek C, et al. Comparison of disinfection proce-
dures on the catheter adapter-transfer set junction.
A. Catheter migration out of the pelvis Peritoneal Dialysis Int. 2016;36(2):225–7.
B. Constipation and faecal loading 7. Kwan TH, et al. Ultrasonography in the management
C. Omental wrapping of the catheter of exit site infections in peritoneal dialysis patients.
D. Fibrin Nephrology. 2004;9(6):348–52.
8. Kirmizis D, et al. Exit-site relocation: a novel,
E. All of the above straightforward technique for exit-site infections.
Answer: E. Perit Dial Int. 2019;39(4):350–5.
Poor drainage may be due to any of these 9. Wong FS. Use of cleansing agents at the
causes however the most common and easily peritoneal catheter exit site. Perit Dial Int.
2003;23(2_suppl):148–52.
treatable is faecal loading and should be 10. Morimoto K, et al. The impact of intraperitoneal
aggressively treated. antibiotic administration in patients with perito-
10. Polycystic kidney disease patients should not neal dialysis-related peritonitis: systematic review
be treated with PD due to the high risk of and meta-analysis. Renal Replacement Ther.
2020;6:1–6.
hernia and lack of space in the abdomen? 11. Schaefer F, et al. Intermittent versus continuous intra-
A. True peritoneal glycopeptide/ceftazidime treatment in chil-
B. False dren with peritoneal dialysis-associated peritonitis. J
Answer: B. Am Soc Nephrol. 1999;10(1):136–45.
12. Chow KM, et al. Predictive value of dialysate cell 15. Hevia C, et al. Alpha replacement method for dis-
counts in peritonitis complicating peritoneal dialysis. placed peritoneal catheter: a simple and effective
Clin J Am Soc Nephrol. 2006;1(4):768–73. maneuver. Adv Perit Dial. 2001;17:138–41.
13. Crabtree JH, et al. Creating and maintaining optimal 16. Prischl FC, et al. Magnetic resonance imaging of the
peritoneal dialysis access in the adult patient: 2019 peritoneal cavity among peritoneal dialysis patients,
update. Perit Dial Int. 2019;39(5):414–36. using the dialysate as “contrast medium”. J Am Soc
14. Jones B, et al. Tenckhoff catheter salvage by closed Nephrol. 2002;13(1):197–203.
stiff-wire manipulation without fluoroscopic control.
Perit Dial Int. 1998;18(4):415–8.
Kidney Transplantation:
The Pre-Transplantation Recipient
21
& Donor Work-Up
Pankaj Jawa, Prabir Roy-Chaudhury,

and Roberto Ceratti Manfro
Clinical Scenario patients already on dialysis. The transplant

A 55-year-old woman with diabetic nephropathy evaluation is a screening process to exclude
and sarcoidosis and declining kidney function, patients for whom transplant will be detrimen-
eGFR 20 mL/min/1.73 m2 was referred for pre- tal [1, 2] (Table 21.1).
emptive kidney transplantation. Her body mass
index was 35 kg/m2 and blood pressure
130/75 mmHg. What investigations would she Referral for Kidney Transplantation
need as part of her kidney transplant work up?
The education for kidney transplant should start
once the eGFR <30 mL/min/1.73 m2 [2]. At this
Introduction time, necessary vaccinations and cancer screen-
ing are performed (Table 21.2). Patients could be
Recipient Evaluation referred for preemptive transplantation when the
eGFR is <20 mL/min/1.73 m2. If a living donor is
Patients with End-Stage Renal Disease (ESRD) available, the time that it takes by the transplant
have a few treatment options. Renal transplan- program to evaluate the donors should be consid-
tation is undoubtedly the one that provides ered. Efforts should be made for a preemptive
more prolonged survival and better quality of kidney transplant, especially in countries where
life and must be offered for suitable patients preemptive deceased donor transplantation is not
with CKD stage 5 progressing to ESRD or allowed, to put patients on the waiting list early
to minimize their time on dialysis.
P. Jawa Recipient Evaluation Team

University of North Carolina, Chapel Hill, USA
P. Roy-Chaudhury (*) The journey from transplant evaluation to sur-
University of North Carolina, Chapel Hill, USA gery can be very tiring for patients requiring
WG (Bill) Hefner, Salisbury VA Medical Center, multiple visits with providers from various disci-
Salisbury, NC, USA plines. The evaluation time will depend on their
e-mail: prabir_roy-chaudhury@med.unc.edu comorbidities. The transplant team involves
R. C. Manfro health professionals from different fields who
Federal University of Rio Grande do Sul, have experience and understand the complexity
Porto Alegre, Brazil
https://doi.org/10.1007/978-3-031-09131-5_21
422 P. Jawa et al.
Table 21.1 Contraindications for a kidney transplant Table 21.3 The transplant team
Absolute contraindications for a kidney transplant, Transplant team
but are not limited to: • Transplant surgeon—to evaluate for any surgical
1. Active infections such as tuberculosis. issues.
2. Active substance abuse • Nephrologist—to evaluate for any medical issues
3. Severe cardiac, vascular, pulmonary, or other • Transplant co-ordinator—primary contact for the
comorbid conditions that create an unacceptable risk patient to help navigate through the transplant
for transplant surgery or immunosuppression process
4. Factors limiting the candidate's ability to adhere to • Social worker—to assess socio-economic
medical care post-transplant, such as living condition.
situation, active mental illness, or psychosocial • Financial co-ordinator (optional)—to get medical
condition. insurance clearance.
5. Malignancy with prognosis suggesting an • Pharmacist (optional)—to educate the patient
anticipated survival of <5 years about medications post-transplant.
Relative contraindications for a kidney transplant, but • Psychologist (optional)—to evaluate for mental
are not limited to: disorders
1. Active infection (HIV, HCV, HBV, tuberculosis) • Dietician (optional)—overweight and
2. Active systemic diseases such as Good pasture’s underweight patients
Syndrome with the persistent presence of anti-GBM
antibodies, Systemic lupus erythematosus, or
Antineutrophil cytoplasmic antibodies.
3. BMI >40% of transplants. The role of a recipient evaluation
4. Inadequate social support system team is to provide constant support and encour-
5. Malnutrition
6. Frailty
agement to the patient and help them understand
and navigate the evaluation process (Table 21.3).
The team must frequently meet to address patient
Table 21.2 Vaccinations and Cancer screening
needs and clear them medically and surgically
Pre-transplant vaccinations: for transplant. It is also necessary to evaluate if
– Tetanus/diphtheria (Td)
– Pertussis (Tdap) the patient has adequate social support and
– Influenza vaccine (yearly) means to support visits and medications
– MMR post-transplant.
– Pneumococcal vaccine (recommended with a
booster every 3–5 years)
– Neisseria meningitides (MCV4. For patients at
high epidemiological risk) Transplant Recipient Testing
– Hepatitis A, hepatitis B
– Varicella vaccine—Varivax (seronegative The necessary cardiac screening and work-up for
patients)
– Polio (inactivated/live-activated) infectious diseases follow a thorough medical
– HPV (Females 9–45 years and males 9–26 years history and physical examination. Additionally,
and MSM > 26) transplant centers can determine their required
Do not administer to post-transplant patients. and optional testing based on the local environ-
– Varicella-Zoster
– Influenza (live-attenuated) ment and demographics of the population they
– MMR serve (Tables 21.4 and 21.5).
– Polio (live-attenuated)
– Tdap (Td was >5 years ago)
Cancer screening:
– Pap smear (Women >21 years) omorbid Conditions in Renal
C
– Mammogram (Women >40 years) Transplant Recipient
– Colonoscopy (> 50 years)
– PSA (Men >50 years) Cardiovascular Disease
– CT chest (for patients >30 pack-years of
smoking) In many developed and developing countries,
– Renal ultrasound (long dialysis vintage, cystic CVD is the most common cause of death at all
disease, or strong family history) points post-transplant. The risk factors are older
– Cystoscopy (long history of tobacco or use of age, pre-existing CVD, time on dialysis, and
cyclophosphamide)
– Ultrasound liver (history of cirrhosis of liver) diabetes mellitus. Most of the deaths occur
21 Kidney Transplantation: The Pre-Transplantation Recipient & Donor Work-Up 423
Table 21.4 Pre-transplant evaluation required testing CAD is very prevalent in CKD and ESKD
Transplant recipient required testing patients compared to the general population.
– ABO compatibility CKD patients undergoing transplant evaluation
– HLA typing and anti-HLA antibody screening
– Complete blood count—TLC with differential,
should undergo a comprehensive screening with
Hemoglobin, Hematocrit, Platelets. either non-invasive or invasive testing. There are
– Complete chemistry panel—sodium, potassium, no uniform guidelines from various medical soci-
bicarbonate, urea or blood urea nitrogen, eties (Table 21.6). The assessment will depend
creatinine, calcium, PTH
– Liver function tests—AST, ALT, Total bilirubin,
mainly on the history of diabetes and cardiovas-
Direct Bilirubin, Total protein, Albumin. cular disease. In patients without diabetes or
– Serum/Urine toxicology screen. other risk factors, the cardiovascular review
– HbA1C or 2-h glucose tolerance test could be limited to history, physical examination,
– Hepatitis A IgG, Hepatitis B surface antigen, b
core antibody, Hepatitis C antibody, HIV antibody.
and electrocardiogram. However, the presence of
– Type and screen for blood risk factors determines further assessment by
– VDRL, CMV IgG, echocardiogram and stress test (treadmill or
– Coagulation panel (PT, INR, PTT) dobutamine) or nuclear imaging. A long history
– PPD (TB skin test) or interferon-gamma release
assay (IGRA)
of diabetes and the presence of cardiovascular
– Beta HCG (women of childbearing age) risk factors may require an evaluation by a cardi-
– Chest X-ray ologist and possible cardiac angiography [2, 3].
– Electrocardiogram Recipients with heart failure due to left ven-
– Abdominal ultrasound or computed tomography
tricular systolic or diastolic dysfunction should
undergo evaluation by history, physical examina-
tion, chest X-ray, electrocardiogram, and echo-
Table 21.5 Pre-transplant evaluation complementary
optional testing cardiogram. Like CAD, there is a need to
Optional testing
determine the etiology of cardiac dysfunction
– Alkaline phosphate, uric acid, fasting lipids, and work on the risk factors. It also includes
glucose, magnesium, phosphorus. looking at dialysis adequacy and volume control.
– EBV, HSV, HTLV, Varicella, Toxoplasmosis, The presence of LVH and higher LA volume are
Rubella, Strongyloides, T. Cruzi, West Nile,
Chagas disease.
independent predictors of death in patients who
– Cardiac ECHO or Stress test (depending on age are wait-listed for renal transplantation. AST and
and comorbidities) Canadian guidelines do not recommend listing
– 24-h blood pressure monitoring for kidney transplantation alone in patients with
– Hypercoagulable work up (history of bleeding,
thrombosis, miscarriages)
severe irreversible (non-uremic) cardiac dysfunc-
– Cardiology clearance (patients with a history of tion. [see Chap. 11 for more information].
CAD, arrhythmia, abnormal cardiac imaging tests).
– Transplant psychologist (history of mental Cerebrovascular Disease
disorder, e.g., depression or anxiety)
– Nutrition assessment (uncontrolled diabetes,
The rate of patients hospitalized with stroke is
BMI >40%, frailty, weight loss, undernourished) markedly higher for dialysis patients compared
– Cystoscopy (cyclophosphamide exposure) to the general population even after adjustment
– Pulmonary function tests with pulmonary consult for age, gender, and race [4]. The risk continues
(patients with COPD)
– CT angiography of abdomen and pelvis and
to be increased close to 8% even after renal trans-
lower limbs (vasculature evaluation) plant. The main predictors are age, peripheral
vascular disease, and diabetic nephropathy.
Similar to cardiovascular evaluation, there is a
within 30 days post-transplant. In the pre-trans- need for the identification of patients at a high
plant evaluation, it is needed to identify moder- risk of cerebrovascular disease and work on risk
ate to high-risk patients and work on their risk modifications such as the use of statin therapy.
factor management, such as treatment of hyper- The patients’ evaluation should include an elec-
tension, hyperlipidemia and stop cigarette trocardiogram, carotid Doppler +/− CT of the
smoking. head, or MRI. Carotid endarterectomy indica-
424 P. Jawa et al.
Table 21.6 Guidelines from transplant societies for car- tions are similar to the general population. As per
diovascular evaluation
Canadian guidelines, kidney transplantation
Canadian guidelines:
1. All patients should be assessed for the presence
should be deferred in patients with a history of
of ischemic heart disease with an ECG and a stroke or transient ischemic events for six months
chest radiograph following the event.
2. Further testing for IHD depends on the pretest Patients with autosomal dominant polycystic
probability of coronary artery disease (CAD).
The following patients should have further
kidney (ADPK) disease have 4 to 5 times higher
non-invasive testing: prevalence of intracranial aneurysm. The guide-
• Symptomatic patients or patients with a prior lines suggest screening patients with ADPK dis-
history of CAD, including: ease and a family history of an intracranial
– Previous history of myocardial infarction
(Grade A)
aneurysm, history of headaches, or those who
– Symptoms of angina (Grade A) have an at-risk activity. Evaluation by MRA or
– Signs or symptoms of congestive heart CT angiogram is indicated for high-risk patients,
failure (Grade A) and neurosurgery should be consulted for further
• Asymptomatic patients with:
– Diabetes (type 1 or type 2) (Grade B)
assessment and management. The intervention is
– Multiple risk factors for CAD (3 or more) recommended if the size of the aneurysm is
(Grade B): >7 mm.
Age >50 years
Prolonged duration of chronic kidney
disease
Peripheral Vascular Disease
Family history of CAD (first-degree Peripheral vascular occlusive disease after renal
relative) transplantation has been associated with lower
Significant smoking history 10-year patient and graft survival [5]. The risk
Dyslipidemia (high-density lipoprotein
level <0.9 mmol/L or total cholesterol
factors are age, preoperative peripheral vascular
>5.2 mmol/L), BMI ≥ 30 kg/m2 disease, diabetes, and smoking. There is a higher
History of hypertension incidence of peripheral arterial disease and death
3. A cardiologist should assess all patients with a in patients waiting for a kidney transplant. At the
positive non-invasive test to undergo
angiography (Grade B).
time of transplantation, abnormal toe brachial
4. Very high-risk patients should be considered for index and history of diabetes are the most signifi-
angiography even with a negative non-invasive cant risk factors for proximal foot amputation.
test (Grade C). The vasculature should be evaluated by Doppler’s
KDIGO guidelines:
1. All patients evaluated for kidney transplantation
or computed tomography of the abdomen, pelvis
should undergo assessment for the presence and and lower limbs for all high-risk patients such as
severity of cardiac disease with history, physical diabetics or with a history of claudication.
examination, and electrocardiogram (ECG).
2. Patients with signs or symptoms of active
cardiac disease (e.g., angina, arrhythmia, heart
Malignancy
failure, symptomatic valvular heart disease) Patients with ESKD and on dialysis have a higher
should undergo an assessment by a cardiologist risk of cancer than patients not on dialysis, espe-
and be managed according to current local cially kidney and bladder cancer. The mortality
cardiac guidelines before further consideration
for a kidney transplant.
among transplant recipients with a history of can-
3. Asymptomatic KTCs at high risk for coronary cer is 30% higher compared to other patients.
artery disease (CAD) or reduced functional Therefore, transplant candidates should be
capacity undergo non-invasive CAD screening. screened for cancer, depending on their age and
4. Asymptomatic KTCs with known CAD not be
revascularized exclusively to reduce
risk factors.
perioperative cardiac events. Patients with a malignancy history have a
5. Exclude candidates with advanced triple vessel waiting time from 2–5 years after their curative
coronary disease from kidney transplantation. treatment, depending on the type and stage of
However, the risk of a post-transplant major
cardiac event should be a significant
cancer; some malignancies do not require a wait
consideration and discussed with the candidate time prior to transplantation (Table 21.7). The
Table 21.7 Malignancy with no waiting time m2 and super obese as >35 kg/m2. For candidates
Malignancies with no waiting time (KDIGO of Asian ethnicity, obesity is defined as a BMI
guidelines) >27.5 kg/m2. As per WHO, waist to hip ratio of
• Non-melanoma skin cancers (surgically or
otherwise treated)
>0.85 for women or >0.9 for men is considered
• Small renal cell cancer (<3 cm) obese. Obese patients have a similar graft sur-
• Prostate cancer (Gleason score ≤6) vival compared to non-obese patients; however,
• Carcinoma in situ the risk of DGF is higher. Most of the transplant
• Thyroid cancer (follicular/papillary <2 cm of
low-grade histology)
centers do recommend weight loss before trans-
• Superficial bladder cancer plantation; however, the threshold for a kidney
transplant is dependent on the transplant center
and its policies. Most centers decline patients
Table 21.8 Malignancy and its recurrence risk
with BMI >40 kg/m2 and recommend some inter-
Recurrence vention for weight loss.
Cancer risk
Incidental renal cancer 1%
Uterus (body) 4%
Age
Testicular cancer (including seminomas, 5% At all ages, renal transplantation offers a substan-
teratomas, embryomas, tial survival advantage over dialysis. In patients
choriocarcinomas, mixed cell, and older than 60, the 5-year survival is 90% com-
unclassified tumors)
pared to 27% for patients on dialysis. However,
Cervix of uterus 6%
one-year survival is almost similar between the
Thyroid and other endocrine tumors 7%
Colon Cancer 21% two groups. Therefore, elderly patients should be
Prostate cancer 18% considered for transplant if their life expectancy
Lymphoma (Hodgkin’s and 11% is >2 years. Currently, as per SRTR (Scientific
Non-Hodgkin’s) Registry of Transplant Recipients) data, 23.8% of
Malignant Melanoma 21% wait-listed patients are 65-year-old or older.
Wilm’s tumor 13%
Age alone can be misleading in transplant
Breast Cancer 23%
Clinically apparent or symptomatic renal 27%
recipient evaluations. Elderly patients should
cancer undergo a frailty assessment by Hopkins frailty
Bladder cancer 29% phenotype scoring. Frail alone increases the risk
Kaposi’s and other sarcomas 29% of death by two-fold. In the Hopkins phenotype
Multiple myeloma 67% frailty measure, the definition of frailty, as a clini-
Non-melanoma skin cancer 48%
cal syndrome, relies on having three or more fol-
lowing five criteria: unintentional weight loss,
waiting time for cancers after treatment is two self-reported exhaustion, weakness, slow walk-
years for malignancy with low recurrence rates ing speed, and low physical activity.
(1–7%) and 2–5 years for cancers with interme- The cognitive function should also be evalu-
diate (11–21%) and high recurrence risk (>23%). ated in detail, as the ten-year dementia risk is
Cancers such as leukemia have minimal data to 17% for patients 75 years and older.
propose waiting time, and for patients treated for
liver cancer, there is a high rate of recurrence, so I nfections—HIV, Hepatitis B, Hepatitis
renal transplantation is not recommended C, Tuberculosis
(Table 21.8 illustrates common malignancies and
their recurrence risk). HIV
These patients are currently considered for a kid-
Obesity ney transplant if they are compliant with their
KDIGO recommends using BMI or waist to hip medical treatment, have an undetectable viral
circumference ratio to evaluate for obesity. In load for more than six months, CD4 count is
terms of BMI, obesity is defined as BMI >30 kg/ >200/μL, and no opportunistic infections.
426 P. Jawa et al.
The 5-year graft survival in well-controlled Tuberculosis

HIV infected patients is similar to non-HIV There is a risk of reactivation of tuberculosis post-
patients. The antiretroviral regimen should be transplant, especially for those who have the
adjusted and modified before the transplant. latent disease and live in endemic areas. Therefore,
Patients must be adherent and tolerant to HIV all kidney transplant recipients are screened for
medications, and ideally, no significant interac- tuberculosis with either PPD or IGRA. If avail-
tion among antiretroviral and immunosuppres- able, the more sensitive IGRA should be used for
sive drugs should exist. The risk of DGF and the diagnosis of latent tuberculosis. As per
acute rejection is higher, and the risk of de novo European guidelines, patients considered to have
malignancy and infections is acceptable in HIV latent TB infection are defined by:
renal transplant recipients.
–– A 5 mm (renal transplant recipients) or a
Hepatitis B 10 mm (dialysis patients) induration after
The serological status of recipients should be tuberculin skin testing
determined before transplantation. The presence –– Chest X-ray images suggestive of past TB
of HBV DNA or hepatitis B antigen pre-transplant infection
has been associated with an increased probability –– History of prior TB infection that was not
of death from liver disease post-transplant. treated adequately; and
Immunosuppressive therapy may also enhance –– Close contact with infectious patients.
viral replication in both HbsAg positive and neg-
ative patients. Patients with chronic HBV should Patients with latent tuberculosis isoniazid (for
be evaluated further with HBV DNA levels and nine months) or rifampin (for four months) is rec-
ultrasound for cirrhosis. Patients with compen- ommended before transplant for treatment.
sated cirrhosis can be considered for kidney Patients with active tuberculosis should not be
transplantation alone. In recipients with high risk considered for kidney transplantation until they
or HBV reactivation, treatment with entecavir or undergo successful treatment.
tenofovir should be initiated.
Pulmonary Disorder
Hepatitis C Currently, the guidelines recommend screening
Patients on chronic hemodialysis with positive for transplant recipients, similar to the general
anti-HCV antibodies have an increased incidence population. However, Canadian guidelines have
of liver cirrhosis and hepatocellular carcinoma defined criteria for candidates who have pulmo-
leading to increased mortality. Renal transplant nary disease and are not candidates. However, all
recipients with hepatitis C have an increased risk guidelines (AST, European, and Canadian) rec-
of death and graft loss. Therefore, every patient is ommend stopping smoking, as patients who are
screened for hepatitis C before transplant. HCV- current smokers are at a higher risk for periopera-
positive patients should undergo investigation for tive complications (Table 21.9).
liver cirrhosis. Patients should be treated for
Hepatitis C before transplant if they present with Hematologic Disorders
decompensated cirrhosis or extrahepatic mani- Hypercoagulable states undiagnosed before
festations of hepatitis C. In the absence of such transplant have been associated with acute vascu-
conditions, patients may accept a kidney from lar rejections, venous thrombosis, and transplant
HCV positive or negative donors balancing the failure. However, routine hematological screen-
risks and benefits of shortening the waiting time. ing is not recommended for every transplant
Irrespective of the timing, all patients should be recipient. The testing should be limited to patients
treated with the direct antiviral drug. with a history of recurrent venous thrombosis
Table 21.9 Canadian guidelines for patients with pul- States, according to the Organ Procurement and
monary disorders
Transplantation Network data, 38% of the kidney
Canadian guidelines for pulmonary disorders transplants performed in 2019 were from living
1. Patients with the following respiratory
conditions and severity are not candidates for
donors. In Europe, 28% of total kidney transplants
kidney transplantation: were from living donors (Table 21.10).
• A requirement for home oxygen therapy
• Uncontrolled asthma
• Severe cor pulmonale
• Severe chronic obstructive pulmonary disease
Kidney Donation Evaluation
(COPD)–pulmonary fibrosis or restrictive
disease with any of the following parameters: Ideally, living donor candidates should be evalu-
best forced expiratory volume in 1 s (FEV1) ated by a team, preferably separate from the kid-
<25% predicted value, PO2 room air <60
mmHg with exercise desaturation, SaO2
ney recipient team. The kidney donation team
< 90% > 4 lower respiratory infections in the should include a nephrologist and transplant sur-
last 12 months, a moderate disease with geon (both not involved in the recipient’s care),
evidence of progression co-ordinator, social worker, and other optional
2. Patients with moderate COPD–pulmonary
fibrosis or restrictive disease with any of the
members, including dietitians, psychologists, and
following parameters have a relative psychiatrists. The advocate for the living donor
contraindication for kidney transplantation helps a well-informed decision for donation pro-
(Grade C): viding independent information and assuring the
• Best FEV1 25–50% of the predicted value
• PO2 room air <60–70 mmHg
absence of coercion. Every living donor should
• Restrictive disease with exercise desaturation, have informed consent, which details their rights,
SaO2 90% consent for donation, risks involved not limited
to the medical or surgical, and the psychosocial
risk related to donation. Kidney donors undergo a
(dialysis access or thrombosis of the portal, thorough evaluation to identify medical, surgical,
hepatic, mesenteric veins), arterial thrombosis, or psychosocial conditions that may put them at a
family history of thrombosis, and recurrent mis- high risk of chronic kidney disease in the future
carriage. Perioperative anticoagulation can [6, 7]. Every center can modify the testing based
decrease the risk of allograft thrombosis. on the endemic disease in their patient popula-
tion, but necessary work-up should be standard
for any donor (Tables 21.11 and 21.12). There are
Living Donor Evaluation a few absolute and relative contraindications for
donors to donate (Table 21.13).
Living donor kidney transplantation, more fre-
quently than deceased donor kidney transplanta-
tion, provides excellent graft function and, Donor History
depending on HLA compatibility, longer graft lon-
gevity. As per the Global Observatory on Donation A detailed history helps us to understand better as
and Transplant, 36% of 90.306 kidney transplants well as inform donors of their risk of chronic kid-
performed worldwide in 2017 were from living ney disease in the future. During history taking
donors. The number of living donor transplants and laboratory review, if the risk of immediate
were more in Africa, the Eastern Mediterranean, kidney disease is considerable, one should not
and Southeast Asia compared to the Americas and proceed with the donation.
European region. In the United States, the number Donor Medical history: It should focus on
of living donors increased in 2018 and 2019 after their past medical history and their future risk of
being stable for most of the decade. In the United developing the disease, especially diabetes,
428 P. Jawa et al.
Table 21.10 Kidney transplants by world region in 2018. Data from the Global Observatory on Donation and
Transplantation (GODT)
Region All kidney transplants in 2018 LD kidney transplants DD Kidney transplants
Americas 36,541 11,021 25,308
South East Asia 7963 6772 1164
Europe 27,879 7820 20,059
Western pacific 16,315 3823 12,492
Africa 268 268 –
Eastern Mediterranean 1858 1685 173
Data from the Global Observatory on Donation and Transplantation (GODT). LD, living donor; DD, deceased donor
Table 21.11 Required evaluations, testing, and donor follow-up

Complete medical history and physical examination: (including a family history of kidney disease, kidney
stones, gout, lifestyle, habits. Measure blood pressure on at least two occasions)
Testing:
• ABO blood typing
• Human Leucocyte antigens (HLA) class I and II typing
• Pre donation kidney function (glomerular filtration rate):
– Estimate GFR using serum creatinine-based estimating equations
– Confirm with one or more of the following: measured GFR using an exogenous filtration marker
(Iothalamate, iohexol, radionuclides), measured creatinine clearance, eGFR from the combination of serum
creatinine and cystatin C,
– If none available: repeat eGFR with serum creatinine
• Predonation albuminuria:
– Assess albuminuria using albumin-to-creatinine ratio in a spot urine specimen
– Confirm albuminuria with albumin excretion rate in a timed urine specimen or by repeating albumin-to-
creatinine ratio if albumin excretion rate is not possible
• Urine: urinalysis, urine culture, toxicology screen
• Blood: complete blood count—TLC with differential, Hemoglobin, Hematocrit, Platelets.Complete chemistry
panel: sodium, potassium, bicarbonate, urea or blood urea nitrogen, creatinine, calcium, fasting blood glucose
or glycated hemoglobin (hemoglobin A1c) or 2-h glucose tolerance testing, fasting lipid profile, including total
cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides.
• Infection transmission: HIV, Hepatitis B virus, Hepatitis C virus, Cytomegalovirus, Epstein–Barr virus,
Treponema pallidum (syphilis), and other potential infections as per geography and environmental exposures.
PPD or IGRA
• Coagulation (PT, INR, PTT)
• Beta HCG: immediately before donation, women of childbearing age
• Image: chest x-ray, an image of the kidneys and urinary tract
• ECG
• Cancer Screening (as per local guidelines, including):
– Pap smear (women over 21 yo)
– Mammogram (women over 40 yo, should be current within 12 months)
– Colonoscopy (patients over 50)
• Psychosocial evaluation
• Ethical, legal, and policy considerations (respect donor autonomy) at all phases
• Nephrology evaluation for medical clearance.
• Transplant surgeon evaluation for surgical clearance
Post donation follow-up (yearly intervals):
• Blood pressure measurement, body mass index measurement,
• Serum creatinine measurement with GFR estimation and albuminuria measurement
• Promotion of healthy lifestyle (exercise, diet, and abstinence from tobacco
• Promote psychologic health and well-being
• Urine protein quantification
Table 21.12 Optional testing for Donors according to infections is significant, especially for donors
individual characteristics and environmental exposures
from endemic areas to avoid transmission of dis-
Optional testing: ease to recipients.
– Alkaline phosphatase, total protein, albumin,
total bilirubin, uric acid, AST, ALT, fasting lipids,
Surgical history: Should focus on previous
glucose, magnesium, phosphorus. abdominal surgeries, which could cause unex-
– Varicella, Toxoplasmosis, Rubella, pected problems during kidney retrieval—also,
Strongyloidosis, T. Cruzi, West Nile, Chagas any surgery, which was complicated by kidney,
disease and hypercoagulable work up in donors
with a history of bleeding or thrombosis.
ureter, or bladder injury.
– Nuclear medicine kidney scan for evaluation of Social history: a history of smoking (both
split GFR (DTPA, MAG 3) active and passive is essential), excessive alcohol
– Donors older than 50 years: echo and stress intake, intravenous or illicit drug use may have
testing (treadmill test for men, Adenosine Sesti
for women)
caused some other organ damage which may
– CT-angiogram (CTA) need further evaluation.
– 24 h Blood pressure monitoring if needed Family history: the focus should be to identify
– Nutrition assessment (Hypertension, BMI >30%, any genetic kidney disease (such as polycystic
unexplained weight loss)
– Psychosocial evaluation with transplant social
kidney disease) which may manifest in the donor
worker or transplant psychologist. later. Detailed family history may help guide
future risk of illness in the living donor.
Table 21.13 Absolute and Relative Contraindications

for Donation
Risk of Donation
Absolute Contraindications for kidney donation:
– GFR <60 mL/min per 1.73 m2
– Solitary kidney Surgical Risk
– Albuminuria >100 mg/d Living donor surgery is considered safe. Surgical
– History of overt proteinuria or hematuria of mortality is 3.1 per 10,000 donors. The risk of
glomerular origin (except thin basement
membrane)
complications has been evaluated in various
– Age <18 years-old studies to date. As per the European association
– Type 1 Diabetes and Type 2 diabetes, not well guidelines (based on the US transplant registry),
controlled. 16.8% of donors experienced a perioperative
– Active cancer
– Active drug abuse (including alcohol)
complication, most commonly gastrointestinal
– Uncontrolled psychiatric disorder (4.4%), bleeding (3.0%), respiratory (2.5%),
Relative Contraindications for kidney donation: surgical/anesthesia-related injuries (2.4%).
– GFR 60–90 mL/min per 1.73 m2 After adjustment of the demographics, African-
– Type 2 diabetes
– History of malignancy
American are at higher risk of complications.
– Chronic illness The perioperative complication rate at Canadian
– Obesity with a BMI >35 transplant centers was also close to 13%. The
– History of nephrolithiasis re-hospitalization rate following donor nephrec-
– History of hypertension on more than two drugs
or with organ damage
tomy is higher among donors who are older and
– Impaired glucose tolerance have more comorbid conditions.
Medical Risk
hypertension, coronary heart disease, obesity, The risk of ESRD is slightly high compared to
nephrolithiasis. Medical history of cancer is vital non-donors. In one report, the relative risk
along with their medication history (nephrotoxic increased between 3.5 and 5.3 for 15-year kidney
medications such as but not limited to non- failure, according to sex and race. An online tool
steroidal anti-inflammatory drugs). History of (http://www.transplantmodels.com/esrdrisk/)
430 P. Jawa et al.
may be used to estimate the projected lifetime account other risk factors. Candidates with albu-
risk of ESRD in the absence of donation accord- minuria >100 mg/d should not donate.
ing to baseline demographic and clinical charac-
teristics. The projected pre-donation risk can be Hematuria
multiplied by the estimated donation attributable Donors with microscopic hematuria should be
risk to calculate the projected post-donation risk. considered as kidney donors after they have been
However, the absolute risk is generally low. evaluated in detail. In the concomitance of albu-
Moreover, it seems to be no increased risk for minuria (> 30 mg/d), genetic risk, abnormal uro-
chronic diseases such as hypertension, diabetes logic or urinary stone evaluation donation should
or cardiovascular disease, or any adverse psycho- not proceed. In some cases, the evaluation may
social outcomes. In living donors, eGFR at six include a cystoscopy or a kidney biopsy.
months may be an independent predictor for
ESRD. The incidence of ESRD 15 years post- Prediabetes
donation with eGFR <50 mL/mim/1.73 m2 at Living donors with impaired glucose tolerance
6 months mark is 33 per 10,000 donors compared may be able to donate without any significant
to 11.7 donors per 10,000 with eGFR >70 mL/ comorbidity. KDIGO guidelines recommend
min/1.73 m2. considering patients with prediabetes if their risk
of developing diabetes is low and with no other
Pre-Eclampsia comorbidities.
The risk of pre-eclampsia and HTN is double in
female living kidney donors. However, there is BMI >35
no significant risk of preterm birth or low birth There is an increased risk of ESRD in obese
weight. patients. For an increase in BMI >27 kg/m2, there
is a 7% increase in ESRD risk [8]. It is similar for
all donors irrespective of gender, race or baseline
pecial Considerations in Kidney
S eGFR spectrum. Therefore, most transplant
Donors centers are hesitant in considering donors with
high BMI, especially with a higher prevalence of
lomerular Filtration Rate
G metabolic syndrome.
Ideally, donors should have a GFR of 90 mL/min
per 1.73 m2 or greater. When the GFR is between Hypertension
60 and 89 mL/min per 1.73 m2, the decision for Ideally, donors should have normal blood pres-
donation must take into account the demographic sure, as defined for the general population.
and health profile of the donor in relation to what According to the KDIGO guideline, donor candi-
the transplant program considers an acceptable dates without evidence of organ damage and
risk. Donor candidates with GFR less than hypertension controlled to systolic blood pres-
60 mL/min per 1.73 m2 should not donate. When sure less than 140 mmHg and diastolic blood
GFR is asymmetric or in the presence of paren- pressure less than 90 mmHg using one or two
chymal, vascular abnormalities, or urological antihypertensive agents may be acceptable for
abnormalities that do not preclude donation, the donation.
affected kidney should be used for donation.
Gout
Albuminuria Kidney donation is associated with an increase in
Patients with albuminuria <30 mg/d can be con- serum uric acid concentration, which may
sidered for kidney donation. If albuminuria increase the risk of gout. In non-donor popula-
ranges between 30 and 100 mg/day, the donation tions, hyperuricemia is associated with a higher
should be on a case by case basis taking into risk of CKD. In a large kidney-donor cohort
study in the incidence of gout was not increased
in donors; however, donors with gout had more ADPKD. DNA testing can also sometimes help
frequent diagnoses of acute kidney injury, CKD, diagnose or exclude the condition. PKD1 and
and other disorders of the kidney. An increased PKD2 mutation screening, with a good tech-
risk occurred in African Americans, older donors, nique, may help to elucidate whether or not the
and men. Therefore, donor candidates should be donor candidate is acceptable.
asked about prior episodes of gout.
Older Donors Conclusions

For kidney donation, older age is classified as
older than 60 years of age. Kidney donation from It was very important to take a full history and
older donors is a safe surgical procedure. The examine the patient to identify any other issues
long-term result from transplantation from an old such as asymptomatic atherosclerotic artery dis-
living donor is similar to deceased donor trans- ease and active sarcoidosis. She needed a dobuta-
plantation from a younger donor. Therefore, it mine stress test with inducible ischaemia in 3/17
should be considered on a case-by-case basis. For myocardial segments. The coronary angiogram
hypertensive older donors with high blood pres- showed atherosclerotic disease in the left anterior
sure lower than 140/90 mmHg, with no end- coronary artery which was managed with a coro-
organ damage and BMI <30, there is no increased nary stent. She was started on aspirin and clopi-
incidence of kidney disease in the short term. dogrel. Her full blood count, calcium, phosphate,
However, long-term older hypertensive donors liver function tests and chest Xray were normal.
have an increased relative risk of ESRD (HR of She was positive of CMV, EBV but negative for
3.04) 15 years post-donation [9]. The absolute HepB, HepC, HIV. She was listed for kidney
risk of ESRD is minimal. There is no increased deceased donor list 3 months after the coronary
mortality for older donors. angiogram when her clogidogrel was discontin-
ued by cardiologist.
POL1 Genetic Testing
A
There is an increased interest in the transplant
community about the risk of the APOL1 gene in Q uestions
donor candidates with sub-Saharan African
ancestors and its likelihood of nephropathy in the
future. Some centers are testing for the APOL1 1. A 44 year old male, an intravenous drug user
gene in patients of African descent and ruling on haemodialysis with history of incidental
them out for donation with two APOL1 renal risk renal cell carcinoma removed 10 years ago
variants [10]. These kidneys have been associ- was referred for kidney transplantation. His
ated with shorter graft survival and lower post- BP was 170/80, height 168 cm weight
donation eGFR. In terms of cost-effectiveness, it 110 kg. He was on treatment for HIV infec-
is beneficial to prevent the earlier onset of chronic tion with normal CD4 count.
kidney disease in some of the African American What is a contraindication for transplan-
donors. tation in this man?
A. Active intravenous drug use
Family History of Polycystic Kidney B. High BMI
Disease C. High blood pressure
Age-dependent imaging criteria have been estab- D. HIV infection
lished for adults with a family history of ADPKD E. Past history of renal cell carcinoma
(PKD1 or PKD2). In candidates 40 years old or Answer A
older, the absence or a limited number of cysts 2. A 55 year old man with diabetes, hyperten-
on kidney computed tomography or magnetic sion with advanced CKD and eGFR 15 mL/
resonance imaging may be used to rule out min/1.73 m2 was referred for kidney trans-
432 P. Jawa et al.
plantation. What is the best possible test for C. Modulation of the recipient’s immune
screening for coronary artery disease? system by the use of intravenous
A. coronary angiography immunoglobulins
B. CT calcium score D. Organise a paired exchange using the
C. Exercise treadmill test national paired exchange scheme
D. Dobutamine stress test E. Reduction of the B lymphocyte pool anti-
E. MRI of the heart CD20 antibody rituximab
Answer D Answer D, as this is has the best possible
3. Which vaccine should be avoided in the outcome
immediate post transplant period? 7. A 55 year old man with diabetes, hypertension
A. Hepatitis A with advanced CKD and eGFR 15 ml/
B. Influenza min/1.73 m2 was referred for kidney transplan-
C. MMR tation. A dobutamine stress test showed revers-
D. Pneumococcus ible ischaemia in 4/17 myocardial segments.
E. Tetanus What is the best possible test for manage-
Answer MMR vaccine, as it is a live virus ment for possible coronary artery disease?
4. Which of the following malignancies A. CT coronary angiogram
requires a long waiting time before kidney B. Coronary angiogram
transplantation? C. Exercise treadmill test
A. Breast Cancer D. MRI without gadolinium
B. Carcinoma in situ E. Myocardial perfusion scan
C. Non-melanoma skin cancers (surgically Answer A
or otherwise treated) 8. A 55 year old man with diabetes, hyperten-
D. Small renal cell cancer (<3 cm) sion with advanced CKD and eGFR 15 mL/
E. Prostate cancer (Gleason score ≤6) min/1.73 m2 was referred for kidney trans-
Answer A, the rest of the malignancies do not plantation. A dobutamine stress test showed
require any waiting reversible ischaemia in 4/17 myocardial seg-
5. What is not an absolute contraindication for ments. A coronary angiogram showed left
living kidney donation anterior descending artery stenosis which
A. GFR <60 mL/min per 1.73 m2 was treated with coronary stent.
B. History of nephrolithiasis What is next best possible step in
C. Solitary kidney management?
D. Type 1 Diabetes and Type 2 diabetes, not A. Offer no antiplatelet therapy
well controlled. B. Start aspirin and wait 1 year before kid-
E. Uncontrolled psychiatric disorder ney transplantation
Answer B C. Start aspirin and clopidogrel and wait
6. A 57 year old male was willing to donate a 1 year before transplantation
kidney to his wife. His blood group was A+ D. Start aspirin and clopidogrel and wait
and his wife was B+. 3 months, then stop clopidogrel, continue
What is best option to improve graft aspirin proceed to transplantation
survival? E. Start clopidogrel and proceed to
A. Anti-A/B antibody depletion at the time of transplantation
transplantation using PP, double-filtration Answer D
PP/membrane filtration, or selective or 9. A 55 year old man with diabetes, hyperten-
unselective immunoadsorption sion on dialysis was referred for kidney
B. Continue with kidney transplantation transplantation. A dobutamine stress test
without any measures showed reversible ischaemia in 5/17 myocar-
dial segments. A coronary angiogram showed 2. Kidney Disease: Improving Global Outcomes
(KDIGO) Kidney Transplant Candidate Work Group.
triple vessel disease. K/DOQI clinical practice guidelines on the evaluation
What is next best possible step in and management of candidates for kidney transplanta-
management tion. Transplantation. 2010;104:S1–S103. https://doi.
A. Do nothing as patient is asymptomatic org/10.1053/j.ajkd.2005.01.019.
3. Tabriziani H, Baron P, Abudayyeh I, Lipkowitz
B. Plan for coronary stent M. Cardiac risk assessment for end-stage renal dis-
C. Plan for coronary artery bypass graft ease patients on the renal transplant waiting list.
D. Start calcium channel blocker Clin Kidney J. 2019;12(4):576–85. https://doi.
E. Start isosorbide and hydralazine org/10.1093/ckj/sfz039.
4. Seliger SL, Gillen DL, Longstreth W, Kestenbaum
Answer C, will be the most common step though B, Stehman-Breen CO. Elevated risk of stroke
the evidence is not clear among patients with end-stage renal disease.
10. A 45 year old patient was referred for a live Kidney Int. 2003;64(2):603–9. https://doi.
donor kidney transplant from his mother. He org/10.1046/j.1523-1755.2003.00101.x.
5. Sung RS, Althoen M, Howell TA, Merion
has not received his COVID-19 vaccines and RM. Peripheral vascular occlusive dis-
has not suffered from COVID-19. ease in renal transplant recipients: risk fac-
What is the best possible advice for tors and impact on kidney allograft survival.
COVID-19 vaccination? Transplantation. 2000;70(7):1049–54. https://doi.
org/10.1097/00007890-200010150-00010.
A. Avoid vaccination 6. Lentine KL, Kasiske BL, Levey AS, Adams PL,
B. Receive both doses at least two weeks Alberú J, et al. KDIGO clinical practice guideline
before transplantation on the evaluation and care of living kidney donors.
C. Receive the last dose the day before kid- Transplantation. 2017;101(8S):S1–S109.
7. Garg AX, Levey AS, Kasiske BL, Cheung M,
ney transplant Lentine KL, et al. Application of the 2017 KDIGO
D. Receive both doses after transplantation guideline for the evaluation and care of living kidney
E. Receive the second dose a day after donors to clinical practice. Clin J Am Soc Nephrol
transplantation 15: 896–905, 2020. doi: https://doi.org/10.2215/
CJN.12141019.
Answer B, as this gives the best chance for 8. Locke JE, Reed RD, Massie A, Maclennan PA,
immunity Sawinski D, Kumar V, et al. Obesity increases the
risk of end-stage renal disease among living kidney
Test your learning and check your understand- donors. Kidney Int. 2017;91(3):699–703. https://doi.
org/10.1016/j.kint.2016.10.014.
ing of this book’s contents: use the “Springer 9. Ammary FA, Luo X, Muzaale AD, Massie AB,
Nature Flashcards” app to access questions using Crews DC, Waldram MM, et al. Risk of ESKD in
https://sn.pub/cz9Cok. To use the app, please fol- older live kidney donors with hypertension. Clin J
low the instructions in Chap. 1. Am Soc Nephrol. 2019;14(7):1048–55. https://doi.
org/10.2215/cjn.14031118.
10. Mena-Gutierrez, A. M., Reeves-Daniel, A. M.,
Jay, C. L., & Freedman, B. I. (2020). Practical
References considerations for APOL1 genotyping in the liv-
ing kidney donor evaluation. Transplantation,
1. Contra-indications for transplantation. Nephrol 104(1), 27–32. doi: https://doi.org/10.1097/
Dialysis Transpl. 2000;15(suppl_7):5–6. https://doi. tp.0000000000002933.
org/10.1093/ndt/15.suppl_7.5-a.
Management of the Patient After
Kidney Transplantation
22
Madhu Bhaskaran and Shahrzad Ossareh
Clinical Scenario hospital discharge and patient education, post-

A 55-year-old male kidney transplant recipient, operative care, post-transplant clinic visits, com-
4 years post-transplant, presented to the emer- mon clinical and laboratory abnormalities and
gency department with fever, shortness of breath triage, post-transplant medications, post-
and fresh bleeding from the rectum. He was ten- transplant infections, indications for allograft
der over the transplanted kidney. On examination, biopsy and necessary allograft imaging studies. It
he was pale, tired and breathless. His haemoglo- will also discuss management of the failing renal
bin was 54 g/L [previously 100 g/L], creatinine allograft and kidney replacement therapy, long
1024 μmol/L [previously 230 μmol/L], serum term care for patients, and other special consider-
potassium 6.5 mmol/L [previously 5.1 mmol/L] ations in follow-up care.
and platelets 63 × 109/L [previously 120 × 109/L],
tacrolimus 19 ng/L [previously 8 ng/L].
What are next steps in management? Pre Transplant Evaluation
and Factors that Influence Post-
Transplant Care
Introduction
There are several important factors that need to
Kidney transplantation changes quality of life be considered during the short and longer term
and improves survival. Careful management in after kidney transplantation. The consequences
the immediate post-transplant period prevents and management of such factors are discussed as
graft loss due to rejection and infection. Longer follows:
term management maintains quality of life, pre-
vents rejection, atypical infection and malig-
nancy. This chapter will discuss recipient- and Aetiology of Kidney Disease
donor-related factors that influence post-
transplant care, possible peri-operative events, • Availability of native kidney biopsy: it is
important to understand the nature of the
native kidney disease leading to ESKD, that
M. Bhaskaran (*) may have implications for the post-transplant
Northwell Healthcare, New York, USA
e-mail: MBhaskar@northwell.edu course.
• Alport syndrome: this will increase the risk of
S. Ossareh
Iran University of Medical Sciences, Tehran, Iran anti-GBM disease, recurrence of which in a
https://doi.org/10.1007/978-3-031-09131-5_22
436 M. Bhaskaran and S. Ossareh
kidney allograft, can lead to rapid allograft • Co morbidities that require special attention
loss post-transplantion, e.g. Hypertension, diabetes
• SLE: previously thought to have low risk of mellitus, coronary artery disease, congestive
recurrence, however transplant needs to be heart failure including diastolic dysfunction,
delayed until disease is quiescent; There is peripheral arterial disease, obstructive sleep
increasing awareness of recurrence in the apnoea, prior neoplastic disease, chronic infec-
transplant kidney tion, previous/prior immune suppression,
• Paraproteinemia: unrecognized pre-transplant opportunistic infections e.g. HHV8, HIV, hep-
can lead to recurrence and allograft loss early atitis B, hepatitis C, BK virus, cytomegalovi-
post-transplant rus (CMV), Mycobacterium tuberculosis
• Oxalosis: in many instances will require a (MTB), Mycobacterium Avium Intracellulare
simultaneous liver-kidney transplant to avoid (MAI) [1].
recurrence in the transplanted kidney
Practice Point 2
• Be mindful of urinary tract abnormali-
Practice Point 1 ties in younger candidates and obtain
• Obtain as much information about native cysto-urethrography
kidney disease, including prior transplant • Bladder outlet obstruction in anuric
course, any biopsies, recurrent disease dialysis patients may be asymptomatic
• Obtain genetic panel when available— • Ensure immunosuppression-free inter-
where original disease is unknown and val prior to retransplant in candidates
particularly where there has been prior with neoplasia related to immunosup-
rapid allograft failure pression and prior BK virus, CMV, MAI
• Be mindful of missed paraproteinemia, and HHV 8 infections and ensure clear-
Alport syndrome with anti-GBM in prior ance of Parvovirus B19 viraemia in col-
allograft, oxalosis variants with partial lapsing glomerulopathy related to it
enzyme deficiency, Fabry disease • Invasive screening for coronary artery
disease may be prudent in candidates
who have uncontrolled or prolonged
diabetes mellitus, other vascular dis-
o-Morbidities that Affect Post-
C eases and/or a long dialysis vintage
Transplant Care
• Urinary tract abnormalities: if these are not

recognized pre-transplant, they may cause: Table 22.1 summarises important members of
urinary obstruction (posterior urethral valve); the post-transplantation multi-disciplinary team:
recurrent urinary tract infection (vesico-
ureteric reflux); abnormal allograft function Table 22.1 Establishing communication among collab-
(neurogenic/poorly functioning bladder) orative multi-disciplinary post-transplant care team
• Pre-Transplant medical/social issues can • A multidisciplinary team including a primary
interfere with adherence to medical advice nephrologist, dialysis center, pre-transplant care
and medication e.g. cognitive impairment, team, transplant nephrologist and transplant
surgeon, pre- and post-transplant coordinators,
psychiatric illness, substance misuse
primary care provider
• Duration of chronic kidney disease (CKD)/end • Cardiologists and other specialists may be required
stage kidney disease (ESKD): This may for proper management in the peri- and early
increase cardiovascular risk post-transplant period
22 Management of the Patient After Kidney Transplantation 437
Table 22.2 Crossmatch methods CKD risk factors, cold ischemia time (CIT)
• Pre-transplant complement-dependent cytotoxicity and anatomical factors such as accessory renal
(CDC) crossmatch: detects alloantibody that binds vessel(s) and ureter(s).
and is cytotoxic to donor lymphocytes, in the
presence of complement
• Flow cytometric crossmatch: detects antibody that
binds to donor lymphocytes, but does not assess eri-Operative Events Which Affect
P
cytotoxicity Post-Operative Care
• Solid phase assay for donor specific antibodies:
Detects the presence of antibody without additional
information on lymphocyte binding or cytotoxicity Cold ischemia time, delayed graft function, ana-
• Virtual crossmatch: Information on details of donor tomic issues such as small accessory renal artery
HLA and most current recipient antibody repertoire, from the donor that could not be anastomosed,
without any sensitizing events in the interim allows for
a ‘virtual’ crossmatching remotely without needing
leading to loss of renal tissue, hypotension, com-
either donor or recipient tissue or blood samples. plications such as ureteral obstruction, leak, vas-
cular thrombosis or stenosis.
Assessment of the Immunological

Risk of Transplantation urgical Complications that May
S
Affect Post-Transplant Management
Sensitizing events in the recipient such as blood or
platelet transfusion, infections requiring hospital- Transplant surgery involves anastomosis of the
ization, pregnancy and prior transplants should be donor arteries and veins with those of the recipi-
noted, and may lead to panel reactive antibodies, ent, and the donor ureter with the recipient urinary
donor specific antibodies. This makes a pre-trans- bladder. As with any anastomosis, leaks and par-
plant virtual and/or physical cross match impor- tial or complete blockage are the main complica-
tant, and may highlight a need for desensitization tions. Manifestations will vary, depending on the
therapy. Table 22.2 summarises the different meth- degree and duration of leaks and the severity of
ods for Cross matching before transplantation [1]. stenosis. Prior condition of the recipient and donor
blood vessels, recipient bladder and donor ureter,
and preservation of its precarious blood supply are
onor Factors that May Influence
D important factors that affect the surgical outcome.
Post-Transplant Management Injuries occurring to the donor prior to or during
organ procurement can greatly impact the usabil-
It is important to take into account donor related ity of the organ and complexity of the surgery.
factors, that may affect outcome in the recipient, Enthusiastic cleaning of the donor ureter off its
remembering that ‘All kidneys are not equal’: surrounding fat tissue by the procuring surgeon is
Consider that the best possible serum creatinine often blamed by recipient surgeon for future isch-
for a prospective DCD donor may be 150 μmol/L emic damage to the ureter which becomes a major
in both a tall, muscular 45-year-old male, and sim- issue to deal with, often causing urine leak and
ilarly in a short, hypertensive 65-year-old female. necessitating surgical interventions. Urine leak
can lead to allograft dysfunction, and sometimes
resolves with placing a nephrostomy and drain
onor Related Factors that Can
D from the collection, longer term bladder catheter
Influence Post-Transplant and ureteral stent with gradual removal of the
Management Include hardware over time allowing the ureter to heal. If
ureteric leak is severe due to ischemic damage of
• Live donor: HLA mismatches, age, need for long segment of donor ureter, this may necessitate
desensitization, lymphocyte depleting re-anastomosis of the kidney to the bladder
induction through sometimes utilizing recipients’ own native
• Deceased donor: deceased cardiac death ureter: a structure that surgeons often complain to
(DCD), High KDPI donor, donor age, donor be a harden to find and harder to mobilize.
An accessory renal artery to the lower pole of should be included in communication in the
the donor kidney, if too small and hard to salvage transition between inpatient and outpatient care
during transplant surgery may be the harbinger of 8. Clear and simple education and reference mate-
a compromised donor ureter. rials, listing post-transplant medications and the
warning signs of potentially serious events that
would require urgent medical attention
Discharge and Education 9. Transition of care to outpatient care teams,
with a clear discharge summary and post-
Patient education is absolutely key to post- operative follow-up care needs
transplant success. Such education starts during
the transplantation work-up phase, but the time in
hospital after the kidney transplantation should Practice Point 3
be utilized as best as possible when patient are • Establishing consistently smooth com-
alert and pain-free. The following issues can be munication amongst all providers and
addressed prior to discharge: caregivers
• The transplant recipient is integral to
1. Special attention to polypharmacy and sus- their optimal post-transplant care
ceptibility to medication errors • Ensuring a high level of adherence with
2. Transplant care being active, and complex medications and follow-up care is nec-
compared to passive and relatively simple essary for optimal outcomes in sensi-
self-care during dialysis tized recipients, and previously known
3. The need to establish consistent and accessi- non-adherent recipients who have lost
ble contact for post-operative care and prior allografts prematurely
communications • Young age, prior substance mis-use, psy-
4. The potential need for a care-giver with ade- chiatric illnesses and prior non-adherence
quate skills that are complementary to the are risk factors for non-adherence
transplant recipients’ own abilities
5. The need to identify barriers to optimal care,
such as a language barrier, cognitive ability,
comorbid psychiatric issues, transportation Post-Discharge Care
issues and substance mis-use (Table 22.3)
6. The need to identify and work with social The following issues should be considered dur-
determinants of health to achieve optimal ing outpatient clinic visits: Whilst the COVID-
outcome pandemic has heralded a much greater demand
7. Specific issues that need to be followed-up for the flexibility and inexpensive nature of tele-
post-discharge, such as the need for ureteric phone consultation clinics. No doubt that the
stent removal, imaging abnormalities requiring need for face-to-face consultations to help to
follow-up, e.g. peri-nephric collections—all build a good rapport and trust between patient
and clinician is also acknowledged.
Table 22.3 Addressing Barriers to optimized care • Post-operative outpatient clinic schedule:
Very frequent to start with 2-3 times a week
Clinicians should be aware of:
• Cognitive impairment and then less frequent but at regular intervals.
• Caregiver issues • Any need for post-operative home visits in-
• Non-adherence with medications, medical advice person or via Telehealth to check medication
and follow up visits
adherence, wound check, vital signs check
• Language barrier
• Psychiatric issues • Education of home care giver and collabora-
• Issues with mobility and transportation tion with home care giver for optimized care
• Medical coverage and financial issues including and monitoring
poverty, food security and homelessness
• Home glucose, weight, urine put, temperature, Weight, urine output, blood pressure, glucose
blood pressure checks and flow sheets levels, medication side effects, surgical wound
• ‘Pill box’ filling and monitoring of adherence characteristics suggestive of healing vs. poor
• Lab test request; education regarding accurate healing and infection
trough level check of immunosuppressive agent Blood counts, blood chemistry including
• In person home visit or Telehealth check Calcium, Phosphate, magnesium; urinalysis,
regarding any warning signs needing to proper urine protein/creatinine ratio; Trough levels of
office visit or laboratory check/imaging study immunosuppressive agents—Tacrolimus,
• Coordination of care with other involved pro- Sirolimus, Everolimus or Cyclosporin.
viders such as endocrinologist, cardiologist, Monitoring for opportunistic infection—BK
psychiatrist, primary care giver and primary virus PCR in blood; CMV PCR in blood follow-
nephrologist. ing cessation of antiviral prophylaxis.
are Plan at a Post-Transplant Clinic

C Practice Point 4
Visit • An abnormal urinalysis with presence
of blood is common immediately post-
A comprehensive post-transplant clinic visit may
transplant, but special attention to a per-
address all of the following over a period of time:
sistently high urine protein:creatinine
Acute symptoms: Fever, Pain, Urinary symp-
ratio needs to be paid in order to recog-
toms—dysuria, hematuria, decrease in urine out-
nise recurrent focal segmental glomeru-
put, nocturia, frequency; GI symptoms—diarrhea,
losclerosis (FSGS) at the earliest
constipation, nausea, vomiting, symptoms sugges-
possible stage
tive of prostatitis in males; Wound-related pain,
discharge, bleeding, oedema, shortness of breath,
symptoms suggestive of worsening co morbidities
Quality of life symptoms: Sleep disturbance; Imaging follow-up of allograft imaging post-
Activity limitation, incontinence, sexual dysfunction, op or previous imaging abnormalities such as
driving limitations, vision changes, skin changes lung nodules/thyroid nodules, pancreas cysts,
Factors affecting Longevity of the recipi- naive kidney cysts, adrenal nodules.
ent: Coronary artery disease, chronic infections,
opportunistic infections, potentially life threaten-
ing infection ost Clinic Visit Lab Review
P
Factors affecting Longevity of the allograft: and Follow-Up
Medication adherence, achieved best allograft
function, recurrent disease in the allograft, Changes in response to immunosuppression
delayed allograft function, rejection episodes, trough levels that are sub- or supra-therapeutic;
closer immune monitoring of sensitized recipi- electrolyte abnormalities and changes in allograft
ents; Opportunistic infections affecting function.
allograft—BK virus, Aden, CMV, Parvo virus. Often warranted are—Changes in immuno-
suppression dose, repletion of magnesium,
phosphorus, potassium, managing hyperkale-
btaining Standardized Clinical
O mia, managing hypercalcemia from hyperpara-
and Laboratory Data at Each thyroidism, changes in cell counts warranting
Encounter changes in dosages of anti-proliferative agents
when low and evaluation for possible infection
The following clinical and laboratory data should when elevated. Table 22.4 summarises a typi-
be collected and analysed during each visit for cal post- transplantation clinic follow-up
optimal care. schedule.
Table 22.4 Post-transplantation clinic follow-up schedule • Low blood pressure and Orthostasis:
The schedule can be variable and may need to Dehydration and hypovolemia, antihyperten-
individualized; an example schedule is as follows, and sive side effect, adrenal insufficiency
may be adjusted to suit needs:
• Twice weekly for the first 2 weeks post-transplant
• Hyperglycemia: New onset or poorly con-
• Once weekly for weeks 1–2 trolled diabetes mellitus
• From 1st to 3rd month every 2 weeks • Hypoglycemia: Iatrogenic, adrenal
• From the following 3 months, monthly till the end insufficiency
of the first year
• Then every 2 months until end of second year,
• Diarrhea: Mycophenolate toxicity, Viral infec-
• Then every 3 months following 2 until 5 years tion—Rota virus, Sapovirus, Clostridium dif-
• Then every 6 months lifelong ficile toxin
• Constipation: Opioid side effect;
A typical model for post-transplantation clinic Hypothyroidism
follow-up is illustrated in Table 22.4: • Abdominal Pain: Urine leak, post-operative
wound infection, calculus cholecystitis, pan-
creatitis, cyst rupture, nephrolithiasis
Practice Point 5
• Fever: Infectious—Urinary infection, oppor-
• End all post-transplant visits by summa-
tunistic infections, pneumonia, post-operative
rizing any medication changes made
wound infection and abscess, Deep vein
during the visit and clarifying any doubts
thrombosis, acute rejection, Post-transplant
and establishing a time line for follow up
lymphoproliferative disorder
visit based on individual circumstances
• Shortness of breath: pulmonary embolism,
• Questions about smoking and alcohol
congestive heart failure, fluid retention,
use need to be carefully repeated at fol-
uncontrolled hypertension
low up visits
• Increased urine output: hyperglycemia,
hypercalcemia
• Urinary frequency: small bladder, prostatism,
ommon Clinical and Laboratory
C ureteric stent related
Abnormalities and Triage • Hematuria: Retained clots in bladder, native
kidney related-cyst rupture, Urinary tract
The causes of frequently encountered clinical infection, ureteral stent related, BK virus
and laboratory abnormalities are as follows: infection, urinary bladder calculus
• Decreased urine output: Dehydration,
Hypovolemia, low blood pressure, acute
Clinical rejection
• Urinary retention: Prostatism, neurogenic
• Rapid weight gain: Fluid retention: dependent bladder, bladder calculus
oedema, elevated blood pressure, orthopnea • Dysuria: Urinary tract infection, hematuria,
and exertional dyspnoea. Increased risk of ureteral stent related, Interstitial cystitis
post-transplant new onset diabetes mellitus if • Stent extrusion
non fluid weight gain
• Oedema: Fluid retention, Deep vein thrombo-
sis, Congestive heart failure, Side effect of med-
ications—nifedipine, amlodipine, sirolimus Practice Point 6
• Weight loss: New onset diabetes mellitus; • Based on the time interval following
Poor appetite or severe diarrhea with malab- transplant, prioritize enquiry during the
sorption, Mycophenolate toxicity post-transplant visit for potential major
• Elevated blood pressure: Need to restart antihy- likely issues affecting allograft and
pertensive, Tacrolimus toxicity, Acute rejection, patient outcome
Transplant renal artery stenosis, Fluid retention
Blood Chemistry
• Special attention to quality-of-life issues
as well as medication side effects and • Hyponatremia: Water intoxication, Urine leak,
personal biases will ensure improved Hypothyroidism, Thiazide therapy
adherence • Hypernatremia: Dehydration, osmotic diure-
• New onset diabetes is easily missed in sis from hyperglycemia, polyuria from
transplant recipients hypercalcemia
• Dysuria without urinary infection is often • Hyperkalemia: Tacrolimus and cyclosporin
reported in presence of haematuria. toxicity, urinary retention, NSAID use, hae-
molysis, rhabdomyolysis, dehydration /
hypovolemia
• Hypokalemia: Polyuria related to hyperglyce-
Complete Blood Count mia, hypercalcemia, diuretic use
• Acidosis: Calcineurin inhibitor related Type 4
• Leukopenia: Viral infections—CMV, renal tubular acidosis, urinary retention, renal
Mycophenolate toxicity, Thymoglobulin insufficiency
• Leukocytosis: Bacterial infections, corticoste- • Alkalosis: Diuretic use, hypovolemia
roid related, lymphoproliferative disorder • Abnormal liver function tests: Elevated trans-
• Anaemia: Related to chronic kidney disease, aminases, bilirubin, GGT:
Mycophenolate toxicity, Parvo B19 infection, –– Drug induced-mycophenolate, azathio-
T cell proliferative disorder, hemolysis, related prine, calcineurin inhibitor related
to dapsone use, Thrombotic microangiopathy –– Infection-related: CMV infection, viral
• Erythrocytosis: Post transplant erythrocytosis, hepatitis, cholecystitis, underlying liver
renal cell carcinoma disease
• Thrombocytopenia: Mycophenolate toxicity, • Non-therapeutic tacrolimus/cyclosporin
Thymoglobulin related, Thrombotic trough levels: Adherence issues, diarrhoea
microangiopathy and constipation, co-intake of medications
leading to interruptions, erratic absorption
related to prior bowel surgery, food
Practice Point 7 interactions
• Carefully review for trends in abnormal- • Elevated creatinine: acute rejection, urine
ities and schedule shorter interval fol- leak, urinary retention, hypovolemia, vascular
low-up to avoid life threatening issues, transplant renal artery stenosis or iliac
situations such as severe neutropenia or artery stenosis, elevated calcineurin inhibitor
thrombocytopenia level, Infections such as pyelonephritis, viral
• Special attention to decreasing haemo- infections—BK virus, CMV, Adeno virus,
globin in recipients with significant cor- Parvo virus
onary artery disease • Nephrolithiasis , bladder outlet obstruction—
• Ensure native kidney imaging to look for mechanical or functional , drug toxicity—cal-
renal cell carcinoma (RCC) and trans- cineurin inhibitor, NSAIDs, contrast-related;
plant renal artery doppler to rule out ste- thrombotic microangiopathy (TMA), post
nosis prior to initiating ACEI/ARB transplant lymphoproliferative disorder
therapy in erythrocytosis post-transplant (PTLD)
Imaging Abnormalities
Practice Point 8
• Special attention to trend in creatinine Ultrasound with Doppler
since I has low sensitivity at high GFR • Imaging indicated for evaluation of elevated
levels. Be mindful of rejection when creatinine, hematuria, changes in urine output,
Tacrolimus level is sub therapeutic with hypertension, recurrent urinary infections, fol-
a rise in creatinine low up of prior abnormal findings.
• Careful with Tacrolimus (or Cyclosporin) • Fluid collection: lymphocele, urinoma,
and Sirolimus combination therapy since hematoma
Tacrolimus toxicity can occur even with • Elevated velocity: Transplant renal artery ste-
otherwise therapeutic levels nosis, Iliac stenosis, transient post-operative
• Repletion of low magnesium • Tardus Parvus wave form abnormality: trans-
(<1.5 MEq/L) or phosphorus plant renal artery stenosis
(<2.5 MEq/L) may be due to elevated • Elevated Resistive indices: Intrarenal pathol-
Tacrolimus level but likely need to be ogy, acute rejection, Acute tubular necrosis
repleted • Decreased resistive indices: Transplant renal
• An elevated Ca (>12 MeQ/L) with ele- artery stenosis, hypovolemia
vated iPTH level will necessitate • Reversal of flow in transplant renal artery:
increased hydration and possible treat- Transplant vein obstruction
ment with Cinacalcet • Hydronephrosis: Full calyces from distended
• A low WBC count (<2.5) or low platelet bladder with ureteral reflux; bladder outlet
count may necessitate adjustment or or obstruction, transplant ureteral obstruction
discontinuation of mycophenolate ther- from stricture, stone or edema
apy. Neutropenia if severe (<500) and • Native kidney lesions: Complex cyst, neo-
persistent may warrant growth factor plasm, source of recurrent urinary infection
therapy involving GMCF.
CT scan: In further evaluation of fluid
collections
PET scan: Post transplant lymphoprolifera-
Microbiology tive disorder
• Bacteriuria, candiduria, Viral PCR for Epstein

Barr virus, CMV, BK virus, West Nile virus Pharmacology of Transplant care:
• Serologies: Crypto antigen, Galacto mannan,
Beta D Glucan Immunosuppression
Induction agents:
Lymphocyte depleting-Thymoglobulin,
Practice Point 9 Campath (alemtuzumab)
• Check CMV PCR following discontinu- Non depleting: Basiliximab
ation of Valganciclovir prophylaxis Maintenance immunosuppression:
since this is a risky time period for CMV Calcineurin Inhibitors: Tacrolimus,
resurgence with clinical disease Cyclosporine
• CMV IgG if negative is less reliable in mTOR inhibitors-Sirolimus, Everolimus
recipient candidates since it has less Co stimulatory Blockade: Belatacept
sensitivity in end stage kidney disease Combination regimen post transplant:
patients Tacrolimus (Cyclosporin) + Mycophenolate
(+ Prednisone)
Tacrolimus (Cyclosporin) + Sirolimus (+

Prednisone) Practice Point 12
Belatacept + Everolimus (+ Prednisone) • 1 year (preferably indefinite) duration of
Belatacept + Mycophenolate (+ Prednisone) prophylactic use of co-trimoxazole
Belatacept + Tacrolimus (Cyclosporin)+ • 3 months of anti-fungal prophylaxis
Mycophenolate (+ Prednisone) • 6 months of anti-CMV prophylaxis.
(Dapsone or Atovoquone can be used in
those allergic to cotrimoxazole
• Short term (1 year) use of Lamivudine
Practice Point 10 and indefinite Entecavir or Tenofovir
• mTOR inhibitor without Calcineurin treatment is recommended in recipients
inhibitor or Prednisone (Only who receive hepatitis B core antibody
Sirolimus+ MMF) has been associated positive organ, and those recipients who
with a poorer long-term outcome. are Hepatitis B surface antigen positive
• When in combination with an mTOR
inhibitor, it is advised to use lower
Tacrolimus (Cyclosporin) target trough Antihypertensive Agents:
levels • Calcium channel blocker—Nifedipine, amlo-
dipine—drugs of choice in the immediate post
transplant period
• Beta blockers—Metoprolol, carvedilol, ateno-
Immunosuppression Target Trough levels are lol, Labetalol
summarized in Table 22.5. • Vasodilators-Hydralazine, Minoxidil
• Centrally acting-Clonidine
• ACEI/ARB: Enalapril, lisinopril, ramipril,
Losartan, Valsartan, Olmesartan. To be used
Practice Point 11
later ideally after 3 months when kidney func-
• 2 hour post dose cyclosporin levels (C2)
tion is stable.
are used in some countries with higher
• Diuretics: Furosemide, Bumetanide,
target levels but lead to overall higher
Hydrochlorothiazide
cyclosporin dosing and no clear benefit
• Alfa blockers-Tamsulosin, Doxazosin
to improve allograft outcome
Agents to Treat Diabetes Mellitus:

• Insulin-short acting and long acting, continu-
Antimicrobial Prophylaxis: ous infusion pump
• Cotrimoxazole-Pneumocystis, urinary infec- • Metformin
tion, Listeria • DPP 4 inhibitors: Sitagliptin, Linagliptin,
• Anti-fungal: Nystatin, Fluconazole, used only Saxagliptin
in special cases • GLP1 agonists: Liraglutide, Exanetide,
• Antiviral: Valganciclovir for CMV Dulaglutide
Table 22.5 Immunosuppression Target Trough Levels

Tacrolimus: Early 8–10 ng/mL Toxic >15 ng/mL Minimum therapeutic level: 3 ng/mL. (With
MTOR inhibitor: 2.5 ng/mL)
Long term: 4–6 ng/mL
Cyclosporin: Early 200–300 ng/mL. Toxic Long term: Minimum Therapeutic: 100 ng/mL (With MTOR
>350 ng/mL 100–200 ng/mL inhibitor: 50 ng/mL)
• Sulfonylurea-Glipizide, Glimepiride
• Meglitinides-Repaglinide, Nateglinide Practice Point 14
• SGLT 2 inhibitors-Canagliflozin and • Always review entire medication list at
Empaglifozin each post transplant visit and have recip-
ients carry a list of all they take including
over the counter and any traditional
Practice Point 13 medications such as herbal supplements
• Though SGLT2 inhibitors are found to
have many benefits in diabetics, their
use in kidney transplant recipients is yet
to be widespread for fear of urinary tract Post-Transplant Infections
infections
• Continuous glucose monitoring with or The common infections associated with time post
without the use of an insulin infusion kidney transplantation are summarized in
pump is becoming more widespread, Table 22.1 [2].
with obvious advantages
• If post-operative period insulin require-
ment is >20 units per day at discharge, it Urinary Tract Infections
would be preferable to maintain them on
a lower insulin-containing regimen on Bacterial: E. coli, Pseudomonas, Klebsiella.
discharge initially ESBL E. coli will need often parenteral
therapy
Fungal: Candida-oral, esophageal, urinary
tract, systemic
Other Agents: Recurrent, resistant and life-threatening infec-
Antiplatelet agents-Aspirin tion should prompt additional studies including
H2 blockers and PPI: Famotidine, omepra- imaging, cystoscopy, reduction in
zole, Pantoprazole immunosuppression
Stool softeners and Laxatives
Antimicrobials:
Antibiotics Pneumonia
Anti fungal agents
Antiviral agents Bacterial: Pneumococcal, Gram negatives
Note: All attempts must be made to follow any MTB: In endemic areas, be vigilant for resis-
deceased donor blood, urine and any tissue cul- tant MTB
tures to inform post-transplant antimicrobial MAI: Ensure resolution prior to re-transplant
regimen especially blood and urine cultures. if pre-existent
Drug–Drug major interactions with
Calcineurin Inhibitors (CNIs):
Rifampicin Fungal
Erythromycin, Clarithromycin
Fluconazole, Ketoconazole, Voriconazole Pneumocystis: Prevention better than treatment.
Food–Drug interactions with CNI are summa- Low threshold for diagnosis tests if not on
rized in Table 22.6. prophylaxis
Aspergillus: Can be life threatening
Table 22.6 Food–Drug interactions with CNI Mucor: High mortality; Surgical approaches
Clinicians should be aware of the following: are often necessary for resection of infected
Grapefruit areas
Fruit punch
Viral Systemic Infections
BK Virus MTB: In endemic areas, high suspicion.

Untreated latent TB needs treatment pre trans-
BK Virus infections characterized in its mild plant. Prolonged treatment and drug resistance
form by BK viruria and low grade transient BK are to be kept in mind.
viremia and in severe form interstitial nephritis Candida: Severe life-threatening infection
and rapid loss of allograft function has become necessitating withdrawal of Immunosuppression
an important factor in allograft longevity. and systemic anti-fungal therapy can occur.
Treatment strategy involves reduction in Nocardia: Can be localized or systemic ilife
immunosuppression, often discontinuation of threatening infection often including nervous
mycophenolate, addition of Leflunomide and system and presenting with seizures
reduced target level of Tacrolimus to minimum CMV: GI tract, lung allograft are often
therapeutic levels and when recalcitrant low dose involved. Be vigilant immediately following ces-
periodic infusions of antiviral agent-Cidofovir sation of prophylactic valganciclovir
which targets virus infested kidney cells acceler- Cryptococcus: Skin, lung and characteristi-
ating their apoptosis through P 53 pathway. cally nervous system can be involved often
Treatment strategy has to be individualized and necessitating prolonged treatment with anti-
should involve transplant professional with expe- fungal agents.
rience in dealing with BK virus infection. EBV: Early post-transplant B-cell neoplastic
Outcome depends on the severity of allograft proliferation can be associated with EBV viremia
dysfunction at the onset, HLA mismatches and and presence in the neoplastic cells
degree of alloimmune response on reducing the HHV 8: Associated with Kaposi’s sarcoma
immunosuppression. and resolution is necessary prior to
re-transplantation
Cytomegalovirus
Localized Infections
CMV infection has highly effective prophylaxis
and treatment options available. Look for drug Fungal: Oral candidiasis , dermatophytic fungi
resistance and combination regimen as may be Nocardia: Can be localized cutaneous, bursa
necessary. Foscarnet is nephrotoxic. Oral Mycobacterium marinum: Often associated
Valganciclovir is used for prophylaxis and treat- with fishing related minor skin injuries
ment of mild to moderate infections and IV
Ganciclovir for sever infections requiring
hospitalization.
Influenza: Seasonal vaccination ; antiviral Practice Point 15
therapy with modest benefit. Can cause multi • Infections can masquerade with mini-
organ failure mal symptoms until severe, fast progres-
RSV: Often associated with leukopenia neces- sion to life threatening condition, with
sitating discontinuation of anti proliferative agent more difficulty in diagnosis and need
Coronavirus COVID 19 Pandemic saw many prolonged treatment for response in
transplant recipients succumb to the infection immunosuppressed host
with others having lung, renal and neurological • High degree of suspicion, microbiology
sequelae sampling of tissues and body fluids and
West Nile Virus: High suspicion and knowl- expert infectious disease input can help
edge of endemicity can help diagnose this early and
quick with potential ability to save the recipient.
Evaluation of Elevated Creatinine:

faster diagnosis and prompt and appro-
priate therapy • Physical examination: signs of dehydration,
• Even with prompt diagnosis mortality is fluid overload
as high as 50% with infections such as • Laboratory studies including urine studies,
Mucor BKV PCR in blood.
• Drastic reduction or discontinuation of • Imaging studies including ultrasound with
immunosuppression to allow host doppler and post void bladder scan
immune system to recover is an integral • Immunological risk evaluation: donor specific
treatment strategy when infection is antibodies, cell free DNA, post-transplant
recurrent, opportunistic and or life cross match
threatening • Allograft biopsy
• Also important is the resumption of
immunosuppression when the infection
is controlled to prevent allograft loss Practice Point 17
• Certain drug interactions such as with • Keep in mind thrombotic microangiopa-
Rifampin and Tacrolimus can precipi- thy, undiagnosed native kidney disease
tate rejection by reducing Tacrolimus such as paraproteinemia
level
Indications for Kidney Allograft

valuation of Fever in Transplant
E Biopsy:
Recipient • For evaluation of elevated creatinine,
proteinuria
The assessment of a febrile patient post-kidney • As part of protocol in a research study
transplant should involve: • Light microscopy, Immunofluorescence study
including C4d, staining for BKV, Electron
• Physical examination microscopy
• Lab data including microbiology • Standardized reporting format for features of
• Imaging studies acute rejection, antibody mediated rejection
• In hospital care and empirical therapy. The (AMR) based on Banff Schema (Fig. 22.2).
common causes of infection are shown in • Protocols for anti-rejection therapy for acute
Fig. 22.1. cellular rejection (ACR), humoral antibody-
mediated rejection (AMR) which may be
predominant findings on a kidney transplant
biopsy
Practice Point 16 • Prompt therapy for thrombotic microangiopa-
• Low threshold for evaluation including thy (TMA), including Apheresis and anti-
full physical examination and work up. complement therapies with prophylactic
Infections can produce less symptoms vaccinations.
due to immunosuppressed star
• Consider opportunistic infections and
non-infectious causes including lym- Anti Rejection Therapies:
phoproliferative disorder and rejection • Steroid pulse 250–1000 mg/dose 3–5 days
• Plain chest radiography is less sensitive • Thymoglobulin 6–10 mg/kg in divided doses
than CT for evaluating for pneumonia
Early Post-Transplant Peak Immunosuppression Late-Onset

0-30 Days Post-Transplant 31-365 Days Post-Transplant >365 Days Post-Transplant
Nosocomial Infections With Prophylaxis Opportunistic Infections

• MDRO: MRSA, VRE, ESLB/CRE • Polyomaviruses • When these occur,
• C. difficile colitis • HCV must consider why they
• Surgical site infections • Cryptococcus neoformans are happening late
• Urinary tract infection • M. Tuberculosis • CMV
• Catheter-related bloodstream • Strongyloides • JC/PML
infections • Leishmania • PTLD/EBV
• Pneumonia • PTLD • Nocardia
Donor-Derived Infections After Prophylaxis Stops Community-Acquired

• Atypical post-transplant course • Pneumocystis Infections
o Examples: LCMV, WNV, • Herpesviruses (CMV, HSV, VZV) • West Nile Virus
T.cruzi, HCV, Bacteraemia, • HBV • Community-acquired
endemic mycoses • Listeria, Nocardia, Pneumonia
Toxoplasmosis • Urinary tract infections
Recipient-Derived Infections • Community-Acquired Infections • Influenza
• Incubating or colonizing • Urinary tract infection • Aspergillus, atypical
o Influenza, Pseudomonas, • Pneumonia moulds
Aspergillus • C. difficile colitis • Hepatitis (HBV, HCV)
Fig. 22.1 Common infections associated with time since encephalopathy, LCMV Lymphocytic choriomeningitis
kidney transplantation [2]. Abbreviations: C. difficile virus, MDRO Multi- drug resistant organism, MRSA
Clostideroides difficile, CMV Cytomegalovirus, EBV Methicillin-resistant staphylococcus aureus, M. tuberculo-
Epstein-Barr virus, ESLB/CRE Extended spectrum beta- sis Mycobacterium tuberulosis, PTLD Post-transplant lym-
lactamase/carbapenem resistant enterobacteria, HBV phoproliferative disease, T. cruzi Trypanosoma cruzi, VRE
Hepatitis B virus, HCV Hepatitis C virus, HSV Herpes sim- Vancomycin-resistant enterococcus, VZV Varicella zoster
plex virus, JC/PML JC virus/progressive multifocal leuko- virus, WNV West Nile virus
• Apheresis (6–10 sessions over 2–3 weeks)for

antibody mediated rejection (AMR)
• Rituximab (for antibody mediated rejection Practice Point 18
(AMR)) • Ensure safe allograft biopsy procedure
• Bortezomib (for antibody mediated rejection with real time guidance, pre-biopsy
(AMR)) studies and post-biopsy monitoring,
• IVIg (for antibody mediated rejection (AMR)) adequate sampling and prompt report-
ing with clinician input for clinical con-
Re-initiation of prophylactic antimicrobial text for biopsy
regimen including for PCP, fungal prophylaxis • Severe irreversible changes of intersti-
and CMV prophylaxis tial fibrosis and tubular atrophy (IFTA)
Follow up care post rejection with shorter should inform and prevent over enthusi-
interval outpatient follow-up and monitoring for astic attempts at immunosuppression
immunosuppression-related side-effects, e.g.
infection, neoplasia
Abbre-
Banff lesion score 0 1 2 3
viation
Interstitial inflammation l <10% 10-25% 26-50% >50

Tubulitis t None 1-4/tubular cross 5-10 >10 or foci of
section or 10 tubular basement
tubular epithelial membrane
cells destruction with
i≥2 and t2
elsewhere
Intimal arteritis£ ≥ v None <25% luminal ≥25% luminal area Transmural and/or
area lost lost fibrinoid change
and medial smooth
musscle necrosis
Glomerulitis g None <25% <25%-75% >75%

Peritubular capillaritis ptc <3 leukocytes/ ≥1 leukocyte in ≥1 leukocyte in ≥1 leukocyte in
PTC ≥ 10% of PTCs with ≥ 10% of PTCs with ≥ 10% of PTCs with
max. of 3-4/PTC max. of 5-10/PTC max. of >10/PTC
C4d C4d None <10% 10-50% >50%

Interstitial fibrosis ci £% 6-25% 26-50% >50%
Tubular atrophy ct None <25% 26-50% >50%
Vascular fibrous Intimal thickening None <25% 26-50% >50%
cv
GBM double contours None 26-50% >50%
cg
Mesangial matrix expansion mm None 1a: only by EM 26-50% >50%

Arteriolar hyalinosis ah None 1b: < 25% by LM Moderate to Severe in many
Hyaline arteriolar thickening aah None £ 25% severe in >1 circumferential
Total inflammation <10% Mild to moderate ≥1 without >50%
ti
Inflammation in the area of IFTA <10% in >1 circumferential >50%
i-IFTA ≥1 without 26-50%
circumferential 26-50%
10-25%
10-25%
Fig. 22.2 Synopsis of the thresholds for all Banff Lesion Scores [3]. Abbreviations: max Maximum, PTC Peritubular
capillary
Thrombotic Microangiopathy with anti-vascular endothelial growth factor

(VEGF) agents.
Catastrophic microvascular pathology involving
injury to endothelial cells and involving fibrin in
capillaries occurs from a variety of causes in apid Recurrence or Occurrence
R
post-transplant period ranging from antibody of Major Allograft Pathology
mediated injury, Calcineurin inhibitor toxicity
and pre-existing genetic susceptibility involving Two diseases that can quickly reoccur after trans-
complement. When prior knowledge of such pre- plant especially with prior recurrence are recur-
disposition can help in the situation in early iden- rent focal segmental glomerulosclerosis (FSGS)
tification of such a phenomenon, the results can and anti-glomerular basement antibody (anti-
still be catastrophic unless prompt actions includ- GBM) disease in an Alport syndrome recipient.
ing intensive apheresis, withdrawal and replace- Prior knowledge of recurrence may help in early
ment of calcineurin inhibitor and institution of diagnosis of these, but treatment of both instances
anti-complement therapy. Such a phenomenon remain less than satisfactory at best. In rare cases,
can also occur with certain interventions in there has been an excellent response to an initial
delayed post-transplant period such as treatment course of Apheresis.
pecial Considerations in Post

S ecipients with Known History
R
Transplant follow Up of Neoplasia
Recipients of High-Risk Donor Organs Apart from ensuring being cancer free at the time
of transplant with an appropriate cancer-free
Recipients of high-risk donor derived organs for interval, long term monitoring plan for recur-
transmission of Hepatitis B, Hepatitis C, HIV due rence identification and prompt intervention is
to well known risk factors in the donors are to be required in this group of recipients who will oth-
followed for these infections in the post-transplant erwise benefit from transplantation.
period for unto 6 months post-transplant mini-
mum and preferably unto 1 year. Certain seasonal/
periodic testing of deceased donors are practiced, Preventive Measures
based on endemicity and seasonal or geographic
variation of diseases such as Zika, Chagas disease Cardiovascular Risk Reduction
and West Nile virus infections.
Smoking cessation, daily physical activity, main-
taining optimized weight, optimized control of
ecipients of HCV Positive Donor
R blood pressure, cholesterol, triglycerides, blood
Organs glucose.
In those with known coronary artery disease
Recipients of known Hepatitis C infected donor or history of coronary re vascularization, anti-
organs (HCV PCR or antibody positive) are to be platelet therapy, beta blocker, statin and lifestyle
followed and tested by blood PCR to confirm modifications as noted above are to be ensured as
HCV transmission and are to be treated until there appropriate [4].
is a sustained viral response using broad spectrum
or genotype-specific anti-HCV regimen and are to
be followed to ensure sustained viral response. Dermatology Surveillance
Skin cancer prevention by reducing sunlight expo-

ecipients with Known Major
R sure and dermatology follow-up and prompt treat-
Psychiatric Illnesses ment of any identified lesions with sometimes
appropriate reduction in immune suppression in
Anxiety, depression, suicide attempts, Bipolar recurrent or severe cases will ensure long-term
affective disorder, Schizophrenia are common optimized outcome in this vulnerable population.
enough to be prevalent among transplant candi- While basal cell cancers are common and innocu-
dates. A well thought out post-operative care plan ous, squamous cell cancers that are invasive and
needs to be incorporated for optimal transplant recurrent, as well as any melanomas are more omi-
outcome in these recipients who do very well nous and could become life threatening.
with such plans in place. Electroconvulsive ther-
apy is particularly advantageous in conditions
deemed beneficial due to its rapidity of onset of Ophthalmology Follow Up
action, lack of drug interactions and ability to
have a high degree of adherence. Depot prepara- Glaucoma and cataracts are common effects of
tions of antipsychotic medications are useful in long-term immunosuppressive regimens, includ-
those instances where pharmacotherapy is the ing corticosteroids and the need for prompt atten-
only alternative. tion to ensure vision preservation. Proactive
monitoring of intra ocular pressure by eye care Travelers

team is essential to early diagnose glaucoma,
which may remain undetected and cause irrevers- Yellow fever vaccine is not recommended for
ible vision loss otherwise. transplant recipients since it is a live virus vac-
cine. Apart from general precautions to prevent
airborne, water, food and insect-borne infections,
Cancer Screening anti-malarial prophylaxis can be safely used by
traveling transplant recipients to malaria-endemic
Age-appropriate cancer screening should con- areas.
tinue post-transplant including prostate, breast,
colon and specifically native kidneys. Though
clear guidelines are lacking, an ultrasound scan ailing Kidney Allograft and Kidney
F
every two years looking at native kidneys seems Replacement Therapy
reasonable and prudent.
The life of a kidney allograft is often shorter than
that of the recipient, even in the best case sce-
ascular Access in a Successful
V nario: extreme levels of adherence and gradual,
Transplant Recipient silent loss of allograft function progresses with
time, necessitating re-transplant when possible. It
Whilst the decision to remove a PD catheter and is clear re-transplant is still the treatment of
tunneled dialysis catheter are fairly simple and choice over various form of dialysis.
obvious, many vascular surgeons are reluctant to Managing immunosuppression as allograft
obliterate functioning arteriovenous fistulae and function declines is an important consider-
grafts, even after a year of excellent allograft ation. Recipients become less tolerant to myco-
function. This needs to be seriously considered, phenolate as anaemia progresses, and this is
especially in recipients with highly developed AV often reduced or withdrawn. There are advan-
fistulae with considerable additional circulatory tages to continuing Tacrolimus and predniso-
load. lone therapy for a recipient who is a
re-transplantation candidate, in that it may pre-
vention of allo-sensitization, which is a strong
Vaccination barrier to re-transplantation. Therefore it can
be recommended to persist with these two
Recommended vaccinations include influenza agents through the next transplant without
vaccine (yearly, seasonal, quadrivalent, high interruption. This is contra-indicated if there is
dose) and pneumococcal vaccines (every a need for an immune suppression-free period
5 years—PPSV 23 and once—PCV 13). to allow resolution of PTLD or HHV-8 infec-
Varicella and measles, mumps and rubella tion, with or without Kaposi’s sarcoma.
(MMR) vaccines are to be given pre-transplant, Persistent BK viraemia despite all other strate-
since they are live vaccines. Varicella Zoster gies may also necessitate weaning of immuno-
(VZV) vaccine, which contains live virus can suppression, as well as a curable neoplastic
be given pre-transplant; killed VZV vaccine is disease requiring chemotherapy, when only
yet to be fully approved in kidney transplant prednisone may be continued while living with
recipients due to its high immunogenicity from a failed allograft.
the adjuvant component. Anecdotally however, These decisions are complex, individualized,
the killed VZV vaccine has been administered and should involve the full post-transplantation
to many transplant recipients, with no major MDT (Table 22.1), including transplantation
reported harm since it has been widely specialists who are well-versed in such
available. scenarios.
The ‘Difficult-to-care-for’ Kidney ist, clinical pharmacist, primary nephrologist,

Transplant Patient transplant nephrologist, transplant surgeon, inter-
ventional radiologist, transplant immunologist,
Transplant care is modelled on a patient-physician Apheresis team, Oncologist, gastroenterologist,
partnership, where honest and forthright communi- Gynecologist, Urologist, Vascular surgeon, oph-
cation is essential for a successful outcome. A sadly thalmologist and dermatologist to name a few.
common scenario is one in which a patient and/or Long term post-transplant follow-up care is a
caregiver (sometimes the parents of a paediatric or labour intensive, and highly involved field, where
transitioning allograft recipient) retains an inherent apparent stability can give way to a l ife-threatening
mistrust of clinical teams—manifesting in non- situation with a short illness. With a fragile popula-
adherence to clinical instructions, constantly chal- tion at the risk of heart disease, neoplasia and infec-
lenging and subverting the advice given—all too tions both recipient and care providers have to be
often leading to suboptimal patient outcomes. on guard at all times to quickly intervene before a
Where the origin of clinician mistrust may be rooted negative situation descends out of control. With
in negative childhood or other experiences, the diligent care over the long term, a gratifying out-
approach in these instances should always be one of come with almost half of all kidney transplant
compassion and empathy, and to avoid blame—a recipients achieving a near-normal lifespan, that is
path which the exasperated treating transplant team both meaningful, productive and enjoyable.
might otherwise follow. Whilst the learning curve
may be unfavourable in some cases, such that suc-
cessful re-transplantation may be either more chal- Conclusions
lenging or practically impossible, it is important to
nurture as positive a learning environment as possi- Post-transplant management requires monitoring
ble for the patient to be able to improve their under- of kidney function, and to investigate the possible
standing and insight into their situation, and thereby causes of any deterioration, which may be revers-
optimize their care. Central to this drive amongst ible. From the initial case study, the rise in serum
the paediatric and young adult transplant patient creatinine in the 55-year-old man could have been
cohort are the advent of Transitional kidney care due to rejection, CNI toxicity, recurrent IgAN; but
services (see chapter 25), cohorting transitioning the low haemoglobin and low platelet count instead
patients in outpatient clinics, and setting up a net- were suggestive of a possible thrombotic microan-
work of ‘model patients’ who may have a similar giopathy (TMA). His tacrolimus levels was high,
background—to act as peer mentors. Similarly, kid- but despite lowering the tarcrolimus dose, his kid-
ney patient associations offer patient support to help ney allograft function did not improve: He required
those at risk. Ultimately all such innovations require haemodialysis; a kidney biopsy performed a week
the voluntary engagement of the patient to ulti- thereafter showed features suggestive of throm-
mately be reflected in improvements with adher- botic microangiopathy (TMA).
ence, and ultimately improved patient outcomes,
and managed on a case-by-case basis.
Questions
ong Term Continuum of Care

L
of Kidney Disease Patients 1. Thrombotic microangiopathy can lead to
devastating injury of kidney allograft. The
Optimal care of kidney transplant recipients following statements regarding thrombotic
involves seamless communication of an estab- microangiopathy are true EXCEPT:
lished team of clinicians, care providers, inpa- A. Genetic basis affecting complement sys-
tient and outpatient providers, including primary tem may be found in patients with throm-
physician, dialysis team, social worker, nutrition- botic microangiopathy
AL GRAWANY
B. Recipient candidates whose native kid- A. Calcineurin inhibitor toxicity is enhanced

neys failed from thrombotic microangi- by coadministration of MTOR inhibitors
opathy have increased incidence of B. While used concurrently with MTOR
thrombotic microangiopathy compared inhibitors target trough levels of
to others when transplanted Calcineurin inhibitors are lowered to
C. Calcineurin inhibitors can cause throm- avoid toxicity
botic microangiopathy C. In transplant recipients with lymphoma,
D. Apheresis and eculizumab are therapeu- Calcineurin inhibitors may be replaced
tic tools that may be used to manage kid- by MTOR inhibitors to take advantage of
ney transplant recipients with thrombotic their anti cancer property
microangiopathy D. Preexisting proteinuria in transplant
E. Thrombotic microangiopathy is a contra- recipients makes them less suitable for
indication for kidney transplantation conversion to MTOR inhibitor based
Answer: E regimen from Calcineurin inhibitor
2. Recipients of allografts can have rapid recur- regimen
rence of disease in the new kidney if the pri- E. Immediate post transplant period is the
mary disease is FSGS and this can lead to ideal time point to start MTOR inhibitors
graft loss. The following statements are True due their wound healing properties
EXCEPT: Answer: E
A. There are reports of transplanted kidney 5. The following statements regarding infec-
with recurrent FSGS got successfully tions following kidney transplantation are
retransplanted quickly to reverse the true except:
process A. Recurrent, life threatening and opportu-
B. Management of recurrent FSGS may nistic infections can be major concerns in
involve Apheresis and Rituximab kidney transplant recipients
C. If native kidneys failed quickly from B. Risk of opportunistic infections are high-
onset of FSGS, the risk of recurrence est in the first month following transplan-
may be higher tation and becomes not a concern after
D. FSGS with genetic basis does not recur 6 months following transplantation
in transplant recipients C. Prophylaxis with Valganciclovir is an
E. Early detection and prompt treatment excellent way to prevent life threatening
guarantees preservation of allograft func- CMV disease in the first 6 months fol-
tion in recurrent FSGS lowing transplantation
Answer: D D. Live vaccines are contra indicated in
3. Features consistent with acute antibody immunosuppressed kidney transplant
mediated rejection in renal allograft biopsy recipients
include the following EXCEPT: E. EBV infection post-transplant is a risk
A. Acute tubular Injury factor for development of Post-transplant
B. Thrombotic microangiopathy B cell lymphoma
C. Glomerulitis and peritubular capillaritis Answer: B
D. Diffuse C4d in peritubular capillaries on 6. The following statements regarding
immunofluorescence Induction therapy in kidney transplant recip-
E. Calcium Oxalate crystals in interstitium ients are true except
Answer: E A. Thymoglobulin and Alemtuzumab are
4. The following statements regarding both depleting antibodies and are power-
Calcineurin inhibitors and MTOR inhibitors ful induction agents used in kidney
are true EXCEPT: allotransplantation
B. Basiliximab is used for treatment of acute B. Native kidney nephrectomy is never

rejection in kidney transplant recipients advised in transplant recipients with
who received it as an induction agent polycystic kidneys
C. Prior exposure to Thymoglobulin can C. Renal cell cancer may develop in poly-
lead to generation of antibodies against it cystic kidneys
making it less effective in subsequent D. Nephrolithiasis and recurrent urinary
instances. tract infections may complicate polycys-
D. Rituximab is not effective in depleting tic kidneys
Plasma cells but can deplete anti CD 20 E. Siblings and parents may be considered
positive B cell lineage cells donor candidates for recipients if they do
E. Special techniques such as CD 19 cross- not have genetic marker for polycystic
match or pronase treatment are used for kidneys
B cell crossmatching in transplant candi- Answers: B
dates who recently received Rituximab 9. Patients with Alport syndrome and end stage
treatment kidney disease may receive successful kid-
Answer: B ney transplants. However the following state-
7. A question on immunological risks – which ments are true regarding these recipients and
of the following statements is true? recipient candidates except:
A. Composite tissue allograft (e.g. face, A. Alport syndrome can affect males and
hands) are likely to induce weaker allo- females
immune response when compared to B. Characteristic lesions seen in Alport syn-
small intestinal allografts drome can recur in kidney transplant
B. Liver kidney dual transplants from the recipients in their kidney allografts
same donor is more likely to induce a C. Anti glomerular basement disease in the
stronger immune response than a kidney allograft is a concern in recipients with
allograft alone Alport syndrome
C. Male offspring donating a kidney to the D. Immunosuppression can mitigate the
biological female parent induces a development of anti GBM disease in recip-
weaker immune response compared to a ient candidates with Alport syndrome
female offspring to the biological male E. Absent COL4A5 protein is a maker for
parent Alport syndrome and can have extrarenal
D. ABO incompatible donor kidney induces manifestations in the form of deafness
a stronger alloimmune response in the and abnormal refraction which will not
long term compared to HLA incompati- improve from receiving successful renal
ble donor kidney transplantation
E. Increased NK cell activity can abolish the Answer: B
tolerance to fetus in pregnancy and can 10. Determining presence of and significance of
cause spontaneous abortion allo antibodies pre and post transplant forms
Answer: E an important advancement in in transplant
8. Polycystic kidney disease is an important immunology over the last two decades.
cause of ESKD, requiring kidney transplan- The following statements about allo anti-
tation to ensure long term survival. The fol- bodies are true except:
lowing statements are true regarding A. Anti ABO antibodies are more signifi-
polycystic kidney disease EXCEPT: cant for allograft outcome than anti HLA
A. Polycystic kidney disease results from antibodies in ABO incompatible trans-
abnormality in ciliary function during plants functioning after 1 year post
organogenesis transplant
B. Complement dependent cytotoxicity T References

cell crossmatch positivity suggests anti
HLA antibodies that are present, binding 1. Abramowicz D, Cochat P, Claas FH, Heemann
U, Pascual J, Dudley C, Harden P, Hourmant M,
and cytotoxic Maggiore U, Salvadori M, Spasovski G, Squifflet JP,
C. Antibodies may appear denovo post Steiger J, Torres A, Viklicky O, Zeier M, Vanholder R,
transplant in HLA mismatched kidney Van Biesen W, Nagler E. European Renal Best Practice
transplant recipients and may lead to Guideline on kidney donor and recipient evaluation
and perioperative care. Nephrol Dial Transplant.
chronic allograft injury through chronic 2015;30(11):1790–7. https://doi.org/10.1093/ndt/
antibody mediated rejection gfu216. Epub 2014 Jul 9.
D. When anti HLA antibodies appear they 2. Agrawal A, Ison MG, Danziger-Isakov L. Long-term
may be accommodated by some trans- infectious complications of kidney transplantation.
CJASN. 2022;17(2):286–95. https://doi.org/10.2215/
plant recipients and this will mitigate CJN.15971020.
allograft damage from them 3. Roufosse C, Simmonds N, Clahsen-van Groningen M,
E. Peritubular capillaritis and diffuse C4d Haas M, Henriksen KJ, Horsfield C, Loupy A, Mengel
staining in peritubular capillaries are M, Perkowska-Ptasińska A, Rabant M, Racusen LC,
Solez K, Becker JU. A 2018 reference guide to the
supportive evidence for antibody medi- banff classification of renal allograft pathology.
ated allograft injury Transplantation. 2018;102(11):1795–814. https://
F. Chronic injury from alloantibodies is a doi.org/10.1097/TP.0000000000002366. Erratum in:
major cause for shortening allograft sur- Transplantation. 2018 Dec;102(12):e497.
4. Chadban SJ, Ahn C, Axelrod DA, Foster BJ, Kasiske
vival in HLA mismatched kidney trans- BL, Kher V, Kumar D, Oberbauer R, Pascual J,
plant recipients Pilmore HL, Rodrigue JR, Segev DL, Sheerin NS,
Answer: A Tinckam KJ, Wong G, Balk EM, Gordon CE, Earley
A, Rofeberg V, Knoll GA. Summary of the Kidney
Disease: Improving Global Outcomes (KDIGO)
Test your learning and check your understand- clinical practice guideline on the evaluation and man-
ing of this book’s contents: use the “Springer agement of candidates for kidney transplantation.
Nature Flashcards” app to access questions using Transplantation. 2020;104(4):708–14. https://doi.
https://sn.pub/cz9Cok. To use the app, please fol- org/10.1097/TP.0000000000003137.
low the instructions in Chap. 1.
Complications of Kidney
Transplantation
23
Mysore Phanish , Pranaw Kumar Jha ,
and Abbas Ghazanfar
tion to kidney transplantation should be consid-

Clinical Scenario ered and analysed with reference to complications
A 55-year-old female with IgA nephropathy, and mortality of patients on dialysis, and those on
with an eGFR of 12 mL/min/1.73 m2 received a the transplant waiting list.
pre-emptive, heart-beating deceased donor kid- Immunosuppression is required to prevent
ney transplantation. Her serum creatinine alloimmune rejection of the kidney allograft.
decreased daily till day 4, when she received her Immunosuppression is initially ‘high’ (induc-
second dose of basiliximab, and was discharged tion), and then reduced gradually to a lower,
home, to be followed up in the transplant outpa- maintenance immunosuppression; details of this
tient clinic twice-weekly. On day 12, her serum can be found in Chap. 22.
creatinine increased by 50 μmol/L. She was Maintenance therapy usually consists of a cal-
admitted from the transplant clinic for further cineurin inhibitor (CNI) (e.g. Tacrolimus or
investigations and management. Ciclosporin), oral steroids, an antimetabolite (e.g.
Mycophenolate Mofetil (MMF) or Azathioprine),
or mammalian target of rapamycin inhibitor
Introduction (mTORi) (e.g. Sirolimus or Everolimus); There is
substantial variation in immunosuppressant regi-
Kidney transplantation is a highly successful ther-
mens between patients and between centres. The
apy for patients with end-stage kidney disease
immunosuppressive regime and the total burden
(ESKD). In this chapter, we focus on complica-
of immunosuppression is tailored according to the
tions of kidney transplantation. It is important to
immune risk, and the risks of infection, cancer
understand that complications described in rela-
and diabetes mellitus. Early steroid withdrawal in
selected group of patients is desirable, in order to
M. Phanish (*) minimise the adverse effects associated with long-
Epsom and St Helier University Hospitals NHS trust, term steroid therapy.
London, UK
e-mail: m.phanish@nhs.net
P. K. Jha utcomes: Patient and Graft
O
Department of Nephrology, Medanta Institute of survival
Kidney & Urology, Medanta—The Medicity,
Gurugram, Haryana, India
Patient and death-censored graft survival are the
A. Ghazanfar
most widely used measures to assess success of a
Trust, London, UK transplant programme. Both early and medium-
e-mail: abbas.ghazanfar@stgeorges.nhs.uk term kidney allograft outcomes are excellent in
https://doi.org/10.1007/978-3-031-09131-5_23
456 M. Phanish et al.
most parts of the world, with steady improvement diabetes mellitus and vascular disease, poor func-
in long term outcomes, but it is widely recognised tional capacity, second and subsequent transplants.
that more work needs to be done to improve long- Although age and obesity are often mentioned as
term outcomes. For deceased donor kidney trans- high-risk recipient factors, good outcomes have
plants, the UK national transplant registry been achieved in older recipients (60–75 years) and
(2019/2020) reports 94% (95% CI: 94%–95%) patients with high BMI (up to 38). Immunological
1-year graft survival and 86% (95% CI: 85%–87%) risk, the degree of HLA matching and sensitisation
5-year graft survival; 97% (95% CI: 96%–97%) status of the recipient, including presence or
1-year patient survival and 88% 5-year patient sur- absence of pre-formed donor specific antibodies
vival (95% CI: 87%–88%). Corresponding figures (DSA), development of de-novo DSAs following
for living donor kidney transplant are 98% (95% transplant have a key influence on rejection rates
CI: 98%–99%) 1-year graft survival and 93% (95% (acute and chronic) and transplant outcomes.
CI: 92%–93%) 5-year graft survival; 99% (95%
CI: 98%–99%) 1-year patient survival, and 95%
(95% CI: 94%–96%) 5-year patient survival. Key urgical Complications of Kidney
S
determinants of graft survival are donor and recipi- Transplantation
ent factors. Higher risk donors are older (>60 years),
have more medical co-morbidities (e.g. hyperten- Figure 23.1 and Table 23.1 describe surgical com-
sion) and suffered a medical cause of death. High plications following kidney transplantation. Most of
risk recipient factors are co-morbidities such as the serious complications such as haemorrhage,
Kidney transplant: Surgical

complications
Vascular Urological Other

complications complications complications
Immediate Immediate Immediate

- Ureteric injury - Graft rupture
- Haemorrhage
- Urinary leak - Wound dehiscence
- Tx renal artery dissection
- Urinoma - Poor perfusion (Kinking)
- Iliac vessel injury
Early Early
Early - Wound infection
- Bladder outflow issues
- Peri-Tx haematoma - Lymphocele
- Urinary fistula
- Renal vein thrombosis - Haematuria
- Ureteric stenosis
- Renal artery thrombosis
Late Late
Late - Ureteric stricture - Incisional hernia
- Pseudoaneurysm - Reflux
- Renal AV fistula - Stone disease
- Transplant RA stenosis
Fig. 23.1 Surgical Complications

23 Complications of Kidney Transplantation 457
Table 23.1 Surgical Complications

Examination &
Presentations and causes Investigations Management
Vascular Complications
Immediate Presentations: Look: Immediate action:
Haemorrhage – Shock – Signs of shock – Clamp the drain
(minutes to – Sudden swelling at site of – Oozing from wound – ABCD
hours) kidney transplant – High drain output – Urgent blood for
– Frank blood in drain Feel: transfusion
Causes: – Pulse – Call for help
– Anastomotic rupture – BP – Transfer to operation
– Anastomotic leak – Abdomen theatre
– Vein rupture Remember: Clamp drain Surgical exploration
Clinical diagnosis to cause tamponade effect – Repair by suturing
– Explant and reimplant
– Pack and re-explore
– Nephrectomy
Technical tips:
– Have kidney back bench perfusion equipment ready for possible exploration and cold
perfusion
– First partially open the muscles of wound and if there is sudden pooling of fresh blood pack
the wound and go higher to take control of common iliac artery. May need transabdominal
approach in rare cases
Early Presentations: Look: General management:
Haemorrhage – Pain and tenderness – Subcutaneous – Arrange blood
(hours to days) – Swelling around transplant swelling around – Dialysis if required
site wound – Stabilize the patient
– External bruising – Bruising around Specific management:
– Dropping urine output abdomen mainly (depends on cause)
– Increase drain blood flanks and thigh – Anastomotic leak
– Dropping Hb – Penile and scrotal – Exploration and surgical
Causes: bruising and repair/suturing
– Anastomotic leak haematoma – Biopsy site bleed
– Biopsy site bleed Feel: – Interventional Radiology
– Bleeding from surgical bed – Transplant site for percutaneous
and kidney hilum – Abdomen with transluminal coiling
scrotum – Exploration and surgical
Listen: repair by direct suturing or
– Bruit over using “plug technique”.
transplant kidney Peri-Transplant bleed
– Bowel sounds – No compression on vessels/
Investigations: small to medium size
– Transplant US haematoma: Usually no
– Plan abdominal CT intervention
– CT Angiogram – Compression on vessels/
– Catheter angiogram Medium to large
To look for: haematoma: Surgical
– Graft perfusion exploration for evacuation
– Peri Transplant of haematoma
haematoma
– Compression on
vessels
Technical tips:
– Plug technique: When biopsy site is more than 2 mm in size suturing the kidney directly can
cause sutures to cut through the tissue and makes bleeding worse and the damaged area
bigger. Therefore, plug technique is more useful as it does not cause tension in sutures. In
this technique first take some interrupted prolene sutures throughout the length of biopsy
hole. Take a piece of fat from subcutaneous or intraabdominal fat and make a plug to seal
the biopsy hole. Then tie all interrupted sutures without tension
(continued)

Examination &
Late Presentations: Look: Mycotic pseudoaneurysms
Haemorrhage – Sudden onset pain – Subcutaneous – Majority of mycotic
(days to – Haematuria swelling around pseudoaneurysms are
weeks) – Shock wound picked on routine scans.
Causes: – Bruising around – Antifungal treatment
– Biopsy site bleed abdomen mainly – Interventional Radiology
– Mycotic Pseudoaneurysm flanks and thigh procedure like stenting and/
– Secondary infection – Penile and scrotal or coiling
Remember: Patients with fungal bruising and – Surgical exploration
positive culture in organ haematoma – Repair
preservation fluid require routine Feel: – Excision and interposition
follow-up with US/CT scans to – Transplant site graft
exclude development of mycotic – Abdomen with – Excision, interposition
pseudoaneurysm scrotum graft and auto-transplant
Listen: – Femoral-femoral crossover
– Bruit over graft
transplant kidney – Nephrectomy
– Bowel sounds – Nephrectomy with repair of
Investigation: arterial defect with
– Transplant US prosthetic patch
– CT scan angiogram – Pseudoaneurysm can
– Conventional present as acute rupture.
angiogram The management is same
– MRI for as management of shock
pseudoaneurysm and acute haemorrhage
To look for: – Management of biopsy site
– Graft perfusion bleed is as described above
– Peri-transplant
haematoma
– Compression on
vessels
– For
pseudoaneurysm
looking for site, size
and flow with
proximal and distal
vascular flow
Technical tips:
– For Mycotic Pseudoaneurysm cases consult with vascular surgical team and have them on
board.
– Keep back bench cold perfusion ready in case of exploration
– Take control of proximal and distal vessels as high as possible before mobilising the kidney
and/or examining the pseudoaneurysm
Transplant Presentations: Look: General management:
Renal Arterial – Intraoperative poor perfusion – Poor and/or patchy – Arrange blood
Dissection of kidney perfusion of – Dialysis if required
– Rarely post operatively transplanted kidney Specific management
presenting as signs and Feel: – Urgent surgical exploration
symptoms of transplant renal – Pulsation in – Graft nephrectomy
artery thrombosis (see Transplant artery
below) Listen:
Causes: – Intra-operative
– Missed retrieval injury to doppler
kidney artery at the time of Investigation:
back bench preparation – Transplant US
– Missed iatrogenic injury at – Contrast CT scan
time of transplant surgery

Examination &
Renal Artery – Within hours to days (usually – Usually, no external – Arrange blood
Thrombosis within 3–4 days) post signs – Dialysis if required
transplantation. Feel: – IV Heparin
– Acute reduction in urine – Tenderness over Specific management
output/anuria, rising graft – Urgent surgical exploration
creatinine, may or may not Investigation: – Commonly graft
have graft tenderness, – Transplant US nephrectomy
Hyperkalemia and raised – Contrast CT scan – Rare, graft rescue by
LDH. – Isotope renogram explanting, back bench
Causes/Risk factors: Remember: Time is very perfusion, reimplantation
– Iatrogenic arterial injury crucial in management.
– Problems with anastomosis Any delays in surgical
– Hypercoagulability/ exploration is associated
Pro-thrombotic state with reduced chances of
– Hypotension organ salvage
– Malposition of kidney
– multiple donor arteries
Renal Vein – Reduction in urine output – Swollen transplant – Arrange blood
Thrombosis and rising creatinine usually site – Dialysis if required
within 7 days post – Swollen ipsilateral – IV Heparin
transplantation. leg Specific management
– Pain, swollen graft and Feel: – Radiological drainage of
tenderness – Tenderness over compressing fluid
– Dropping urine output/anuria graft collection
if occlusive thrombus. – Tender thigh or calf – Urgent surgical exploration
Non-occlusive thrombus may Investigation: – Commonly graft
present more insidiously. – Transplant US nephrectomy
– Painful swollen ipsilateral – Contrast CT – Rare, graft rescue by
leg Urogram with explanting, back bench
– Hyperkalemia. arterial and venous perfusion, reimplantation
Causes/ Risk factors: phases
– Haematoma, lymphocele,
Urinoma causing
compression
– Iatrogenic venous injury
– Problems with anastomosis
– Hypercoagulability
– Malposition of kidney, renal
vein kink
– Ipsilateral ileo-femoral DVT
Technical tips: [Transplant RA or RV thrombosis]
– Keep back bench cold perfusion ready in case of exploration. Use heparin in perfusion fluid.
Generally, 10,000 U in 1L of Soltran solution. Perfuse kidney under pressure
(100–120 mmHg)
(continued)

Examination &
Transplant Presentations: Look and Feel: General management:
Renal Artery – Within months to years – Generally, no signs. – Blood pressure control.
Stenosis – Worsening or new onset May have signs of Specific management
hypertension, fluid retention fluid retention, – Percutaneous transluminal
– Graft dysfunction in the difficult to control balloon angioplasty (PTA)
absence of rejection, drug blood pressure. – Percutaneous transluminal
toxicity, ureteric obstruction Listen: balloon angioplasty (PTA)
and infection – Bruit over with stenting
Causes: transplant site – Surgical intervention
– Suture technique Investigations: – High risk procedure
– Atherosclerotic arterial – Transplant artery – Bypass grafting
disease in donor or recipient doppler USS – Stricturoplasty
– Arterial trauma during organ (Velocity of – Reimplantation
procurement or transplant >200–250 cm/s in Remember: PTA with or without
– Prolonged cold ischemia Tr A usually stenting is treatment of choice
– Arterial kinking indicates significant
– Chronic antibody mediated stenosis)
rejection – Contrast CT
– Cytomegalovirus infection angiogram
– Magnetic resonance
angiography
– Catheter angiogram
To look for:
– Site of stenosis
– Single or multiple
– Extrinsic
Compression on
vessels
Urological Complications
Urethral Injury Presentations: Investigation: Management:
– Difficult male catheterisation – If known before, – Attempt catheterisation, if
at the time of surgery. retrograde not possible use cystoscopy
Causes: urethro-cystogram. and guidewire technique. If
– Unknown enlarged prostate – At time of surgery not possible, consider
not presented before due to can do flexible supra-pubic catheterisation.
oligo-anuria. cystoscopy. – Urology referral
– Unknown pre-existing Remember: Do not attempt
urethral stricture. forced catheterisation

Examination &
Urinary Leak / Presentations: Look and Feel: General management:
Urinary fistula – Urinary leak: High drain – Wound examination – Wound care, stoma bag.
/ Urinoma output during early Investigations: Large defects can have
post-operative period. – Drain fluid for portable vac dressing.
– Urinary fistula: Presenting creatinine levels Specific management
early as above or after taking [will be much – Insert urinary catheter if
the ureteric stent out in higher (mmol/L) not already in. Usually for
which case presents with compared to serum small to medium size leaks
raising creatinine and US creatinine (μmol/L). with drain output upto
finding of fluid collection. – Transplant kidney <500 mL/24 h settles down
Causes: and pelvic US with few weeks of bladder
– Commonly anastomotic leak. – Contrast CT catheterisation.
– Iatrogenic bladder injury. urogram – Nephrostomy will be
– Iatrogenic transplant kidney – Retrograde helpful but difficult due to
renal pelvic or ureteric injury cystogram to lack of hydronephrosis.
demonstrate – If there is large urinoma
contrast leak, not with pressure effects, it will
usually required need per-cutaneous drain.
– Technetium-99m Avoid inserting drain for
MAG3 nuclear small collections as there is
medicine test. significant infection risk.
Remember: Drain fluid – Antegrade or retrograde
creatinine level is key test (uncommon) ureteric
to differentiate between stenting for ureteric or
urinary leak and pelvi-ureteric injuries.
lymphocele – Surgical exploration,
ureteric repair and neo
uretero-vesical anastomosis
which may require a Boari
bladder flap or utilisation
of native ureter for new
anastomosis
Technical tips:
– Small urinary leaks can be treated with bladder catheterisation. Leave the ureteric stent
in-situ until the leak is resolved.
– During surgery retrograde controlled filling of urinary bladder with saline coloured with
methylene blue dye usually helps to identify the area of leak.
Bladder Presentations: Look and Feel: General management:
outflow issues – Urinary retention. – Tender supra pubic – Urinary catheterisation.
Causes: area due to – Trial without catheter.
– Enlarged prostate not distended bladder. Specific management
presented before due to – Dull percussion – Consider alpha blockers.
oligo-anuria note. – Urology referral.
– Pre-existing urethral – PR examination for
stricture. prostate.
– Reduced urinary bladder Investigation:
capacity due to long periods – Urinary bladder
of oligo-anuria whilst on scan to assess
dialysis- Usually leads to urinary volume.
marked frequency and – Transplant and
urgency of urination. bladder US.
– Trans-rectal US for
prostate.
– Check PSA
(continued)
AL GRAWANY

Examination &
Ureteric Presentations: Look and Feel: General management:
stenosis/ – Acute presentation: After – Generally, no signs. – Ensure safe K+
stricture removal of ureteric stent, – Graft tenderness. Specific management
sudden drop in urine output Investigations: – Nephrostomy to bypass
and raised creatinine. – Transplant US obstruction and decompress
– Chronic presentation: – Nephrostomy with pelvicalyceal system
Gradual slow increase in nephrostogram is – Antegrade ureteric stent for
serum creatinine with or gold standard 6–8 weeks followed by
without noticeable change in investigation. surgery
urine output. – Isotope renogram – Recent transplants or
Causes/Risk factors: – CT urogram allografts with good
– Stenosis at the level of To look for: function will require
Ureteroneocystostomy. – Site of stenosis/ ureteric reimplantation,
– Pelvi-ureteric junction stricture which, depending on
stenosis. – Length of stenosis/ length of the stricture, may
– Ureteric stenosis or stricture, stricture require a Boari bladder flap
mainly distal ureter (usually – Single or multiple or utilisation of native
ischaemic due to ligation/ ureter for new anastomosis
sacrifice of lower pole donor – Allografts with poor
artery, rarely in association function or short graft life
with BK Virus infection) expectancy can be managed
– Ureteric kinking by dilatation and antegrade
stenting
Remember: Ureteric
reconstruction surgery is often
very challenging therefore there
should be reasonable graft life
expectancy to attempt this
procedure. Generally, allograft
GFR >20 mL/min with slow
yearly decline rate
Technical tips:
– When planning for surgery, where possible, pre-operative insertion of an anterograde ureteric
stent is helpful for identifying ureter during surgery

Examination &
Lymphocele Presentations: Look and Feel: General management:
– High drain output. – Generally, no – Wound care is key. If
– External swelling at external signs. controlled area can put a
transplant site. – External swelling or stoma bag. Large defects
– Swollen ipsilateral leg (Due ipsilateral lower can have portable vac
to venous limb swelling. dressing.
compression±DVT) Investigation: – Drain care.
– Urinary symptoms frequency – Drain fluid for Specific management
and urgency (Due to bladder creatinine. – If picked up after taking the
compression) – Transplant US to drain out: US or CT guided
– Allograft dysfunction assess size of drain insertion depending
– Incidental finding collection. upon size, site and any
Causes: – CT scan. compression effects on
– Lymph leak from transplant Remember: Mild to surrounding structures
bed dissection. moderate size collections particularly renal transplant
– Lymph leak from renal not causing compression vessels and iliac vessels.
hilum/donor kidney on vessels can be – Low output <250 mL/24 h:
lymphatics. managed conservatively. Can be managed with
– mTOR inhibitors (Sirolimus/ radiological drainage
Everolimus) increase the risk +/− sclerotherapy.
of Lymphocele – Moderate output between
250–500 mL/24 h:
Drainage with
sclerotherapy +/− surgery.
- High output >500 mL/24 h
usually requires surgical
fenestration/marsupialization
either laparoscopic or open.
Laparoscopic creation of
‘window’ in to peritoneal cavity
Technical tips:
– Sclerotherapy: 5% povidone-iodine percutaneous sclerotherapy is commonly used. Through
drain under strict antiseptic measure gently aspirate the lymphocele fluid as much as possible.
Slowly inject 5% povidone-iodine solution into lymphocele cavity (commonly between 50and
100 mL). Clamp the drain and observe the patient. If clinically well keep clamp between 15 and
30 min and then leave it for free drainage. Repeat the process 5–6 times over a period of week to
10 days
(continued)

Examination &
Stone in renal Presentations: Look and Feel: General management:
transplant – Acute obstruction with graft – Generally, no – Analgesia.
dysfunction. external signs – Nephrostomy where
– Transplant pyelonephritis or except tenderness required.
recurrent UTI. over graft. – Small non obstructing
– Urinary symptoms frequency Investigation: stone can be managed
and urgency. – Plane Xray of conservatively.
– Allograft dysfunction transplant site. – Maintain fluid intake of
– Incidental finding – Transplant kidney around 3 L/day and salt
Risk factors/Causes: US to look for restrict. Do not restrict
– Previous history of recurrent hydronephrosis. dietary calcium.
stones in the recipient with – CT scan KUB with Specific management
persistent metabolic contrast. – Extracorporeal shock-wave
abnormalities – Stone profile studies lithotripsy (ESWL)
(Hyperparathyroidism, Remember: Transplant – Percutaneous
hyperoxaluria, hydronephrosis is an nephrolithotripsy (PCNL)
hypercalciuria, low urinary emergency that requires – Ureteroscopy and stone
citrate) nephrostomy to removal
– Ureteral obstruction or decompress the system – Open surgery
chronic urinary stasis and preserve allograft
– Foreign body (especially function
nonabsorbable suture
material)
– Pre-existing stone or tubular
defects in donor kidney
Wound – Uncommon, encourage – Look for signs of Management:
infection weight loss and a BMI of wound infection, – Wound care
<30 pre-transplant to reduce routine blood tests – Antibiotics
the risk including CRP – Optimise glycaemic control
– Diabetes, obesity and – Wound swab for – Radiological drainage of
previous kidney transplant, culture and infected collections as
high level of sensitivity clinically indicated
immunosuppression are risk – Blood culture
factors – US scan to look for
– mTOR inhibitors (Sirolimus any peri-transplant
and Everolimus) are collections
associated with poor wound
healing
Incisional Risk factors Management:
Hernia Obesity, diabetes mellitus, wound – Usually surgical repair as
infection clinically indicated
transplant kidney artery and vein thrombosis are mal clinical signs apart from a rising serum creati-
very rare. It must be noted that allograft dysfunction nine. Therefore, simultaneous consideration of
following kidney transplant can be due to surgical surgical and medical causes of complications, with
complications such as a ureteric leak, or poorly per- systematic clinical, laboratory and radiological
fused kidney, or due to medical complications, such assessments are essential to make the correct diag-
as acute rejection or tacrolimus toxicity, with mini- nosis, and initiate appropriate treatment.
Kidney transplantation is becoming a com- due to technical challenges; a small capacity,

mon procedure for the management of patients very thick or thin-walled urinary bladder, with a
with end stage kidney disease [ESKD]. Over short length transplant ureter is a common sce-
recent years, the incidence of surgical complica- nario. Small leaks are usually from a neo-uretero-
tions has dropped significantly from as high as cystostomy, and can be managed with prolonged
20% between 1960 and 1980 [1, 2], to a current urethral catheterisation, however results of early
incidence of around 5% [3, 4]. The surgical exploration and surgical repair are also good.
complications can generally be divided into Large leaks are commonly due to ureteric necro-
three major categories: vascular, urological and sis, and requires skillful surgery. Ureteric steno-
other complications. Each of these can be fur- sis or strictures can present early due to ischaemic
ther subclassified into immediate, early and late, injury, or late due to chronic scarring, or BK
according to the timing of their occurrence virus infection. Kidneys with poor allograft func-
(Fig. 23.1). tion are often managed by antegrade dilatation
and stenting or long-term nephrostomy, whereas
good functioning allograft kidneys require surgi-
Urological Complications cal reconstruction. Depending on the length of
the remaining healthy donor ureter, the surgical
Urologic complications are the commonest surgi- options include resection and neo-uretero-
cal complication after kidney transplantation, cystostomy, psoas hitch surgery, Boari flap, or
causing significant morbidity and mortality. uretero-ureteric drainage.
In the early era of kidney transplantation, the
incidence of urological complications was as
high as 10–25% [5]; this has reduced signifi- igh drain output post kidney
H
cantly—to 5–7% in recent years [4]. Urinary transplant surgery
leak/fistulae are the most common surgical com-
plications, followed by ureteric strictures and This a common complication, illustrated in
reflux. The majority of urinary leaks present with Practice Points 1 and Fig. 23.2:
a high drain output. Early leaks are commonly
High drain ouput post renal transplant
- Patient stablility and external sings of haemorrhage

- Color and amount of fluid
Aim: differentiate between haemorrhagic and non-
haemorrhagic drain output
Haemorrhagic drain output Non-haemorrhagic drain output

Color: serous/yellow/clear
Patient stable Unstable patient Drain fluid & serum U&E for comparison
Mild blood loss Moderate to severe
blood loss
Resuscitation and
Conservative Urinary leak Lymphocele
definative procedure
management
depending on
aetiology
Conservative Low output

Small quantity
management with < 250ml/24Hrs
< 250ml/24 hrs
urinary Conservative
catheterisation
Moderate
Management depends on site quantity Moderate output
and quantity of leak. Useful 250-500ml/24 250-500ml/24Hrs
investigations are: hrs Sclerotherapy
CT scan with contrast
MAG3 / Tc99 scan
Retrograde cystogram
Nephrostogram Large quantity High output
>500ml/24 hrs >500ml/24Hrs
Surgery
Bladder leak Prolong transurethral catheter
If not resolved
surgical repair
Ureterovesical Leak
Ureteric leak
Ureteric necrosis Ureteric reconstruction surgery
Fig. 23.2 Proposed management algorithm for high drain output post kidney transplant
Practice Point 1
High drain output post kidney transplant surgery
Clinical Scenario:
A 43-year-old female patient with a BMI of 38 kg/m2 on peritoneal dialysis, having a history
of ESKD secondary to ADPKD received her first live donor kidney transplant from a 58-year-
old genetically unrelated ABO-compatible donor. The donor kidney had a small lower polar
artery, in addition to a main renal artery, which was separately anastomosed. She had unevent-
ful transplant surgery, with immediate graft function. From immediately post transplantation,
she had a high drain output, which failed to settle over the ensuing days
Challenges:
This is a common presentation after kidney transplantation: iatrogenic missed peritoneal
membrane injury or injury to a native kidney cyst can confuse the common differential diag-
nosis of urinary leak or lymphocoele. A smaller lower polar artery, if thrombosed, can increase
the risk of distal ureteric necrosis, resulting in a urinary leak. A high BMI is a risk factor for
lymphocoele.
Examination
Haemodynamically stable patients with no additional symptoms except heaviness around the
transplant site. There were no external clinical signs, apart from mild wound tenderness due to
recent surgery. There was straw coloured fluid in the drain.
Investigations
Good allograft function with a stable Hb. Drain fluid showed creatinine of 156 μmol/L, com-
pared to a serum level of 147 μmol/L, which excluded a urinary leak. An ultrasound of her
transplant kidney showed a large peri-transplant collection, which was drained:
a b
Image shows a kidney transplant ultrasound scan, demonstrating a large peri-transplant collection (a,
white arrow), which resolves post drainage (b):
Management
The case was initially managed with instillation of 5% povidone-iodine solution through the
drain, which did not lead to a reduction in drain output, hence surgical laparoscopic fenestration
was successfully undertaken at 28 days post transplantation
Hydronephrosis of the Transplant

Kidney
This complication is uncommon, and is illus-

trated in Practice Points 2 and Fig. 23.3
Hydronephrosis of transplant kidney
Acute: newly transplanted patient Chronic: late presentation
Satisfactory to Poor to less than

Nephrostomy and where possible good graft function satisfactory graft
antegrade ureteric stenting GFR>20 functions
GRF<20
Surgery
Consevative approach
with initial antegrade
dilatation of stricture
and ureteric stenting
Good ureter length Short Ureter followed by retrograde
stent changes on
regular intervals +/–
surgery
New
neoureterocystostomy Psoas hitch surgery
Boari flap
Uretero-ureteric drainage
Fig. 23.3 Proposed plan for management of hydronephrosis
Practice Point 2
Hydronephrosis of the Transplant Kidney
Clinical Scenario:
A 63-year-old male with a history of ESKD secondary to diabetic nephropathy received a
kidney from a 69-year-old deceased donor after circulatory arrest (DCD). After an initial
period of delayed graft function (DGF), he had good kidney transplant function. He had urinary
retention following his catheter removal, and required re-catheterisation, with concomitant
alpha-blockade. He underwent removal of his double J ureteric stent at 6 weeks post transplan-
tation, following which his serum creatinine started to rise, with a dropping urine output.
Challenges:
This case illustrates a common presentation in elderly transplant recipients. In this case, age
and male gender are risk factors for prostatic hyperplasia, that can cause bladder outflow
obstruction. On the other hand, elderly DCD donor kidney has an increased risk of ureteric
ischaemia, and hence ureteric stricture or stenosis. The main challenge in this case is to differ-
entiate between urinary retention due to bladder outflow obstruction, or due to possible ureteric
pathology.
Examination:
Graft site fullness and tenderness can be a sign of kidney pathology, however an enlarged
palpable bladder with suprapubic tenderness and a dull suprapubic percussion note indicates
bladder pathology. Per rectal examination also gives useful information.
Investigations:
Ultrasound of the kidney transplant and urinary bladder, with a post micturition residual
volume is a key primary investigation, that can differentiate between an enlarged urinary blad-
der due to distal obstruction or kidney pelvicalyceal system with a collapsed urinary bladder.
Specific investigations include transrectal ultrasound, CT urogram, and nephrostogram. In this
case, ultrasound showed a hydronephrotic transplant kidney. A nephrostomy, then a nephrosto-
gram was performed, which confirmed distal ureteric stenosis.
a b
Images shows an antegrade nephrostogram, demonstrating a distal ureteric stenosis (a), which is sub-
sequently stented, with distal contrast run-off post ureteric stent insertion (b):
Management:
Bladder outflow issues are mainly due to benign prostatic hyperplasia, and usually respond
well to alpha-blockers. Transuretheral resection of prostate gland is an option for advanced
disease. The management of ureteric strictures or stenosis depends on graft function, site of
pathology and availability of reconstruction choices. Generally, the distal ureter is affected, with
a reasonable transplant ureteric length, a resection of the ischaemic, stenosed segment, and neo-
uretero-cystostomy, with or without a psoas hitch. In case of a short ureteric length, the options
include a Boari-flap, uretero-ureteric (transplant or native) anastomosis, pelvicalyceal-
cystostomy, or rarely ureterostomy. In this case, the patient subsequently underwent a definitive
elective ureteric re-implantation.
Vascular Complications vascular thrombosis require immediate input which

in majority of cases require surgical exploration.
Vascular complication commonly present in early Interventional radiology has also its role in man-
post-transplant period and usually have cata- agement of vascular complications particularly it is
strophic effects of kidney allografts. The preva- useful in management of post-kidney transplant
lence of vascular complications range from 3 to biopsy cortical bleeding, pseudoaneurysms and
15% [2, 4]. Acute complications like bleeding and transplant renal artery stenosis (TRAS) (Fig. 23.4).
a b
Fig. 23.4 Stenting of a transplant renal artery post-trans- procedure on selective arteriography. (b) Post transplant
plant. (a) Transplant renal artery stenosis demonstrated renal artery stenting procedure—good flow and run-off
(white arrow) and post stenotic vessel dilatation pre- distal to the stricture is demonstrated
Practice Point 3
Oliguria post kidney transplant
Clinical Scenario:
A 59-year-old female patient with ESKD secondary to FSGS, with a previous history of
unprovoked DVT, received a cadaveric kidney transplant following donation after brain death
(DBD) from a 49-year-old male donor, with a history of acute kidney injury (AKI) Stage 2 at
the time of donation. The surgery was uneventful, but the patient suffered delayed graft func-
tion. On the 7th post-operative day, she had a percutaneous transplant biopsy. The procedure was
uneventful, but on the same night, she presented with sudden severe pain over her transplanted
kidney, and anuria.
Challenges:
The real challenge in this case is to differentiate between a vascular event, or simple acute
tubular necrosis due to donor AKI. Risk factors for thrombosis are a history of unprovoked
DVT, and potential post biopsy bleeding, compressing on the kidney transplant hilum, causing
renal vein thrombosis.
Investigations: Transplant coloured doppler US remains the first investigation to look for
organ perfusion, vascular flow and haematoma. In equivocal CT angiogram, or MAG3 nuclear
scans can be helpful. In this case, her US showed flow in the renal transplant artery, with rever-
sal of diastolic flow. There was no flow detectable in the renal vein.
a b
Images shows a colour doppler scan of a transplanted kidney. US showed flow in the renal transplant
artery, with reversal of diastolic flow (a). There was no flow detectable in the renal vein (b).
Management:
Once a diagnosis or suspicion of transplant renal vein or renal artery thrombosis is made, it
requires immediate exploration. Any chance of graft salvage depends on how quickly organs
can be re-perfused. In the majority of cases, graft nephrectomy is the only option. Small to
medium sized haematomas, not compressing on kidney vasculature, can be managed with a
conservative approach. In the above case the patient had transplant renal vein thrombosis, which
was not salvageable, and culminated in graft nephrectomy
Oliguria post kidney transplant is described with a management plan with

Practice Points 3 and Fig. 23.5:
Oliguria or anuria with AKI post-transplant is
common, but rarely due to surgical causes. This
Acute oliguria or anuria in immediate period post renal transpalnt
Check: Patients haemodynamic

stability rule out haemorrhage
Vascular problem Urological problem
Transplant doppler US showing poor or

pathcy perfusion, reversal of diastolic Check for haematuria and blocked
flow in renal artery, renal artery or renal catheter
vein thrombosis or compression
Urgent surgical
Catheter flushed and
exploration
Catheter not blocked unblocked to establish
urine outflow +/–
irrigation
Urgent renal transplant

colour doppler US to rule Well perfused kidney
out acute vascular issues with no hydronephrosis:
or hydronephrosis ATN or rejection
Well perfused kidney

Nephrostomy for
with hydronephrosis:
acute rejection and
Ureteric stricture or
further planning
blocked ureteric stent
Fig. 23.5 Management of oliguria and anuria post kidney transplant

edical Complications of Kidney

M • Antimicrobial prophylaxis with
Transplantation Sulfamethoxazole-Trimethoprim (480 mg
once a day) is primarily used for prevention of
Infections Pneumocystis pneumonia but it also provides
some protection against urinary tract infec-
• Infections are more common in transplant recip- tions. CMV prophylaxis with Valganciclovir
ients due to both immunosuppression and com- is given where the donor is seropositive and
monly associated co-morbidities, such as the recipient is seronegative (D+/R−). In some
diabetes mellitus. One should consider the over- centres, seropositive recipients (irrespective of
all immunosuppressive burden of the patient donor CMV status) are given Valganciclovir
(including immunosuppression the patient might prophylaxis, and no prophylaxis is given
have received for their native kidney disease, as where both donor and the recipient are CMV
well as immunosuppression given on induction seronegative.
and maintenance treatment following kidney • Viral and fungal infections tend to be more
transplantation), while assessing infection risk. common in patients who receive lymphocyte
• The infections can be typical or atypical bac- depleting antibody induction such as anti-
terial infections (including mycobacterial thymocyte globulin (ATG), and in particular
infections), viral and fungal infections those who receive higher doses (>3–4 mg/kg).
acquired either in healthcare or community
settings, or reactivation of endogenous infec-
tions such as cytomegalovirus (CMV), vari- Cytomegalovirus (CMV)
cella zoster virus (VZV) or latent Tuberculosis.
Typical early infections are perioperative bac- In kidney transplant recipients, symptomatic dis-
terial infections: wound infections, urinary ease due to CMV is either due to reactivation of
tract infections (often in association with latent disease, donor-derived new infection, or
bladder catheter or ureteric stent) and pneu- infection with an exogenous strain (community
monia. Opportunistic fungal infections acquired). CMV disease in uncommon in the first
(Pneumocystis Jirovecii, Aspergillus, 4 weeks post-transplantation, but not unknown.
Cryptococcus) and viral infections such as Those at highest risk of developing high-grade
CMV usually occur between 1 and 6 months viraemia and CMV disease are D+/R− patients,
post transplantation. hence this is the population targeted to receive
• Early removal of the bladder catheter and ure- Valganciclovir prophylaxis. There are two
teric stent removal between 2 and 4 weeks approaches to prevent and treat CMV infection in
post-transplant is recommended to reduce the transplant recipients: The first is regular surveil-
risk of urinary tract infections. lance blood PCR screening to detect CMV virae-
• In a post-transplant patient with abnormal mia, and to treat pre-emptively if viraemia is
liver function tests, consider CMV infection, detected, or give valganciclovir prophylaxis in
Hepatitis B, C, A and E infections. selected recipients, and treat viraemia detected
• Presentation can be atypical in an immuno- on clinical grounds. Our practice is to give
compromised host. Every attempt should be Valganciclovir prophylaxis to D+/R− patients for
made to obtain an organism from appropri- minimum of 90 days, and do active CMV PCR
ate specimen for early diagnosis and treat- surveillance in seropositive recipients (D+/R+
ment. This may include bronchoscopy and and D−/R+) for 3 months. The immunosuppres-
bronchoalveolar aspirate, radiological sive burden has usually lowered by 3-months
drainage of collections, viral PCRs (poly- post-transplantation, enabling cessation of
merase chain reaction) from blood samples Valganciclovir prophylaxis and surveillance.
in addition to routine blood, urine and spu- Coupled with minimisation of immunosuppres-
tum cultures. sion in low/standard immunological risk trans-
plant recipients (steroid withdrawal on D7, performed at least one week apart. The typical
reduction in mycophenolate mofetil dose from duration of therapy is 2–4 weeks. Upon comple-
1 g BD to 500 mg BD after 30 days, long term tion of treatment, the options are either stop val-
dual immunosuppression in the majority of the ganciclovir and do monthly CMV PCR
patients), we have found that this approach results surveillance for a further 3–4 months or continue
in low CMV infection rates (5–8%), and is cost- prophylactic dose for 3–4 months. If the viremia
effective. Some centres continue prophylaxis for fails to respond to Valganciclovir, viral ganciclo-
200 days in D+/R− patients and also use prophy- vir resistance should be suspected, and appropri-
laxis for all patients except for D-/R− patients. ate resistance gene mutation studies should be
CMV can present in kidney transplant recipi- done. Both the treatment and prophylactic dose
ents as either asymptomatic CMV viraemia or of valganciclovir should be adjusted to estimated
CMV disease. CMV disease is defined as the creatinine clearance or estimated GFR (eGFR).
presence of CMV virus in blood or tissues (usu- Patients with severe disease may require treat-
ally detected in blood by CMV PCR), along with ment with intravenous ganciclovir for the first
clinical features of organ involvement. Usual 48–72 h. Options are limited for gancicloivir
clinical manifestations are hepatitis, colitis (diar- resistant CMV disease and these include
rhoea, with or without blood and mucus), and Foscarnet (toxic drug) and other newer/experi-
haematological (leucopenia). Other rare manifes- mental antiviral drugs such as Marabavir.
tations in severe disease include pneumonitis and There are two approaches to prevent CMV
meningoencephalitis, but these are uncommon in disease: either routine prophylaxis (usually with
the current era of kidney transplantation, where oral valganciclovir ) or routine monitoring for
immunosuppressive burden is usually kept at evidence of viraemia with pre-emptive
modest levels. treatment.
Diagnosis is either made by demonstrating
CMV antigenaemia to detect CMV proteins
(pp65) in peripheral blood leukocytes (isolated pstein–Barr Virus (EBV) and Post-
E
from buffy coat fraction of blood sample) or by Transplant Lymphoproliferative
PCR in peripheral blood sample (obtained in an Disorders (PTLD)
EDTA tube). At our centre, the diagnosis is made
by CMV PCR from whole blood. Higher viral Acute infection with EBV is not usually a clini-
loads are often associated with CMV disease, so cally relevant problem after adult kidney trans-
it is important to have close links with virology plantation, but an important long-term
laboratory as reporting units (DNA copies/mL or complication of EBV infection is the develop-
units/mL) vary widely between laboratories. ment of post-transplant lymphoproliferative dis-
Treatment is a reduction of immunosuppres- ease (PTLD), with an incidence of 0.5–1%.
sion, with or without antiviral therapy. We usu- Although it is usually described that most cases
ally manage asymptomatic CMV viraemia with of EBV-driven PTLD occur within one year post
immunosuppressive reduction alone (usually transplant, cases can occur at any time following
dose reduction or withdrawal of mycophenolate transplantation. The more intense the immuno-
mofetil), but in some patients deemed at high risk suppression used (in particular, lymphocyte
of rejection we treat with oral valganciclovir depleting antibody induction), the greater the risk
without altering their immunosuppression. In of PTLD, and the earlier it tends to occur. There
patients with high grade viraemia associated with is an increased risk of PTLD amongst EBV-
CMV disease, we treat with reduction in immu- negative recipients of EBV-positive donor organs.
nosuppression and oral valganciclovir. The treat- The majority of PTLD develops as a result of
ment is continued until complete resolution of EBV-driven uncontrolled B-cell proliferation, on
signs and symptoms of CMV disease and there is a background of suppressed cytotoxic T cells due
absence of CMV viraemia in two blood PCRs to immunosuppression.
A small proportion of post-transplant lympho- and reduced mycophenolate mofetil exposure),

mas (around 10%) are from EBV-negative we observe low BKV rates of around 2–5%.
B-cells, and these behave clinically like non- BK viruria post-transplant is common, and
Hodgkin’s lymphoma (NHL). The presentation doesn’t always mean a viral infection of the
may be typical of NHL, with symptoms or sys- transplant kidney (BK virus nephropathy,
temic signs such as fever, unexplained weight BKVN). BKVN is usually associated with high
loss, anaemia, fatigue, lymphadenopathy, gastro- grade viremia (positive BKV PCR in blood of
intestinal symptoms (including obstruction), hep- >10,000–20,000 DNA copies/mL), but we have
atosplenomegaly, central nervous system seen cases of BKVN with low grade viremia, and
symptoms or pulmonary symptoms (often with occasionally, absence of a positive viral stain on
nodules on chest X ray). An atypical presentation kidney transplant biopsy specimens in the pres-
in a transplant patient could be unexplained graft ence of high grade viraemia, which can be due to
dysfunction due to lymphoma infiltrating the the patchy nature of the pathology and sampling
transplant kidney, in the absence of generalised error. The diagnosis in such cases can often be
lymphadenopathy or hepatosplenomegaly. This made with repeat biopsy from a different site.
can be mis-interpreted as cellular rejection, and The diagnostic yield is higher if the cortico-
special immunocytochemical stains would be medullary junction or medulla is included in the
needed to differentiate between the two. Usually, biopsy, since BKV has a predilection for the kid-
the interstitial infiltrate is extensive and diffuse in ney medulla.
PTLD. Blood PCR usually reveals high grade The clinical presentation of BKVN is a rising
EBV viraemia. Treatment consists of withdrawal creatinine, with no other clinical features or
or marked reduction of immunosuppression rarely, a ureteric stricture causing hydronephrosis
accepting the risk of rejection and graft loss. of the transplant kidney. The transplant kidney
Rituximab alone, or in combination with other biopsy remains the definitive test to diagnose
standard NHL chemotherapy regimen is often BKVN and immunohistochemical staining for
used to treat PTLD. A close liaison with haemato- BKV (SV40 large T antigen, SV40T stain) should
oncology is essential while managing these be the standard practice. The histological features
patients. include tubulointerstitial inflammation (can be
very similar to rejection) and positive SV40T
stain. An early improvement in serum creatinine
BK Virus (BKV) with methylprednisolone does not exclude
BKVN, as suppression of inflammation associ-
BK virus belongs to the family of polyomavirus ated with viral infection can improve kidney
group and causes tubulointerstitial nephritis and function transiently. Concomitant acute rejection
rarely ureteric strictures in kidney transplant can occur, but treatment should be directed
recipients. towards BKVN once diagnosis is proven with
BK virus infects urothelial (transitional epi- reduction in immunosuppression with further
thelium) and tubular epithelial cells, with no clin- changes dictated by clinical course and where
ical features of systemic involvement outside the necessary, further transplant kidney biopsy.
urinary tract. The virus either comes with the Various BKV screening protocols have been
donor kidney, which harbours latent infection, advocated as viraemia often predates clinical
with re-activation following transplantation due graft dysfunction by several weeks or even
to immunosuppression, or from re-activation of months. One should bear in mind that low grade
latent virus in the recipient genitourinary system. viraemias (usually <2000 copies/mL) detected
The risk factors for BK virus infection include on surveillance PCRs may not be clinically rele-
the degree of immunosuppression, trauma to the vant and reduction in immunosuppression with-
urinary tract and male gender. With a low immu- out a biopsy diagnosis of BKVN could lead to
nosuppressive burden (early steroid withdrawal rejection. Therefore, a biopsy is recommended to
confirm the diagnosis of BKVN before altering obtaining microbiological proof, but every
immunosuppression. attempt should be made to demonstrate the organ-
Urine PCR for BKV is not recommended for ism from sputum (difficult in practice, usually
the diagnosis or monitoring of BKVN. The other need to be induced with saline inhalation) and
test often mentioned in the literature is ‘decoy’ bronchoscopic aspirate. Diagnostic yield is
cells in the urine. These are tubule cells infected enhanced by performing PCR from respiratory
with BKV, and shed in the urine, identified by tract secretions, in addition to conventional stain-
their morphology of ‘large irregular nuclei’ due ing and microscopy.
to viral inclusions but this test is not widely used PCJ in immunosuppressed recipients can be
in clinical practice. life threatening and therefore, prompt com-
The main treatment of BKV is a reduction of mencement of treatment upon high clinical suspi-
immunosuppression. We usually stop mycophe- cion is required. The treatment consists of high
nolate mofetil, maintain the patient on tacrolimus therapeutic dose trimethoprim/sulfamethoxazole
monotherapy while monitoring BKV viral load orally in mild to moderate disease or intrave-
in blood with 2–4 weekly PCRs and add small nously in patients with severe disease. In those in
dose of prednisolone (5 mg once a day) once whom trimethoprim/sulfamethoxazole is contra-
reductions in viral load is achieved. There is no indicated, alternative drugs include clindamycin/
specific antiviral treatment for this condition and primaquine, trimethoprim/dapsone, atovaquone
no randomised trials. The drugs that have been and pentamidine.
tried are a 2-week course of ciprofloxacin and It is routine clinical practice worldwide to give
more recently leflunomide. The leflunomide has prophylactic co-trimoxazole at a standard dose of
in vitro antiviral properties and is immunomodu- 480 mg once a day for 3–6 months to all kidney
latory, is well tolerated and we have observed sta- transplant patients. With this regime, there have
bilisation of graft function in patients with BKVN been marked reductions in the incidence of PCJ
upon treatment with this drug along with reduc- infections in kidney transplant patients.
tion of immunosuppression. Other approaches
that have been tried are- switching calcineurin
inhibitor (CNI) to mTOR inhibitor (Sirolimus/ Mycobacterium Tuberculosis (MTB)
Everolimus) and intravenous immunoglobulin.
Mycobacterium Tuberculosis (MTB) is an impor-
tant opportunistic infection in kidney transplant
Pneumocystis Jiroveccii (Carinii) recipients, with significant variation in preva-
lence in different parts of the world, based on
Pneumocystis pneumonia (PCP/PCJ) is a poten- community prevalence of the disease. Managing
tially life-threatening pulmonary infection that tuberculosis in transplant recipients is challeng-
occurs in immunocompromised individuals. ing in view of the non-specific clinical presenta-
Transplant patients are at highest risk in their tion, interaction of anti-MTB medicines with
first 3 months post-transplant due to higher levels immunosuppressive medications, and higher
of immunosuppression, but the infection can incidence of anti-MTB medicine-related adverse
occur at later stages in patients maintained on effects. The risk factors include a previous his-
higher levels of immunosuppression, and those tory of incompletely treated MTB, underlying
receiving treatment for rejection episodes. In the chronic lung disease, fungal co-infections, diabe-
transplant patient, PCJ typically presents as tes mellitus, poor nutritional status and high
hypoxic type1 respiratory failure, associated with immunosuppressive burden in particular, one that
fever and dry cough, with diffuse and bilateral includes lymphocyte depleting antibody induc-
pulmonary interstitial infiltrates on chest X ray tion. MTB in a kidney transplant patient could
and CT scan. The index of suspicion should be be: (a) endogenous reactivation of latent tubercu-
high and often treatment is commenced before losis infection (LMTB) in the post-transplant
period (b) donor-derived tubercular infection active MTB post-transplant and treat as
(rare) (c) de-novo infection due to exposure to appropriate.
MTB bacilli in the post-transplant period. The 4. Treat with Isoniazid alone (300 mg once a
presentation can be a typical respiratory presen- day), along with pyridoxine for 6 months,
tation of cough, fever, haemoptysis and weight starting at the time of transplant in high- risk
loss, or an atypical presentation with intermittent patient population in low prevalence areas of
fevers, weight loss and predominantly extrapul- the world, without prior screening for latent
monary disease. TB.
At our centre in the UK, we currently adopt

re-transplant Screening for Latent
P option 4. It must be emphasised that option cho-
Mycobacterium Tuberculosis sen should be based on local prevalence and inci-
(LMTB) dence of the disease and one should follow local
expertise and guidelines.
Latent mycobacterium tuberculosis (LMTB) The two commonly used tests for screening
infection has been defined by the world health for LMTB, include tuberculin skin test (TST) and
organization (WHO) as “a state of persistent interferon gamma release assay (IGRA). In the
immune response to stimulation by IGRA test, cytokine interferon (IFN)-gamma is
Mycobacterium Tuberculosis antigen, with no measured as the readout of effector-T cell stimu-
evidence of clinically manifest active MTB dis- lation upon exposure to mycobacterium tubercu-
ease”. The concern in patients with undetected losis antigen in vitro. In immunocompromised
LMTB who get transplanted, is that immunosup- patients, it has the advantage of differentiating
pression could lead to re-activation of the dis- anergy from a true negative test. It is also more
ease. Various guidelines recommend screening specific than TST when used in BCG vaccinated
for the prospective kidney transplant recipients, individuals.
who are deemed to be a higher MTB risk for Active tuberculosis must be ruled out in all the
LMTB pre-transplant, and treating it. The options patients undergoing transplant, evaluation as well
are: as in the post-transplant setting. A detailed his-
tory and clinical examination concentrating on
1. Screen everyone in high prevalence areas of symptoms such as chronic cough, weight loss,
the world and treat if positive. unexplained fever, night sweats should be fol-
2. Screen selected high risk population in low lowed by a thorough lab workup, including
prevalence areas of the world (<20 per microscopy for acid fast bacilli (AFB), tubercular
100,000 population) and treat if positive (for culture in appropriate samples (sputum, urine,
e.g. close contact with TB cases, recently pleural fluid etc.), needle aspirate or biopsy his-
arrived from high endemic regions, spend a tology, Gene Xpert for MTB assay and imaging
significant amount of time in high prevalence such as x-ray chest, ultrasound and CT scan.
parts of the world). More invasive procedures like bronchioalveolar
3. Do not screen anyone in high prevalence parts lavage, pleural and lung biopsy may be required.
of the world, as exposure would continue to
occur following completion of treatment, and
using one or two agents to treat latent TB in reatment of latent and active
T
these regions would promote resistance, Mycobacterium Tuberculosis (MTB)
which already is a significant issue in these
areas of the world. This option is often Whenever feasible LTB treatment should be
favoured in these regions where clinicians opt completed pre-transplant while the patient is on
to treat clinically active MTB pre-transplant waitlist and the treatment of choice is Isoniazid
where possible and watch for any signs of and Rifampicin for 3 months.
As far as the active tuberculosis is concerned, infection followed by aspergillosis, cryptococco-

the ideal scenario would be to completely treat it sis, endemic fungi and zygomycosis. Candida
prior to kidney transplantation, as per the WHO and aspergillus are the common causes in the first
or the local guidelines. However, this may not be three to six months when the immunosuppression
feasible always especially in high prevalence tends to be at a higher level awhile cryptococcal
areas where the dialysis infrastructure is poor and and endemic fungal infections tend to occur at
continuing dialysis could be associated with fre- later stages. Various risk factors for getting fun-
quent complications and higher morbidity and gal infections in post-transplant period include
mortality. Successful outcomes have been the net state of immunosuppression, use of anti-
achieved when transplantation was done after thymocyte globulin (ATG) for induction, diabe-
completing the initial intensive phase (2 months) tes mellitus, prolonged and indiscriminate use of
pre-transplant and then continuing the mainte- antibiotics, central venous catheter, intravenous
nance phase in the post-transplant period. cannulae left in for long durations and prolonged
Standard regime includes 4-drug combination of urinary catheterisation.
Isoniazid, Rifampicin, Pyrazinamide and The clinical picture varies, depending upon the
Ethambutol for 2 months of initiation phase fol- sites affected and can include gastrointestinal
lowed by 4-month continuation phase with tract, lung, urinary tract, respiratory tract, blood
Isoniazid and Rifampicin. Patients with extra stream and central nervous system involvement.
pulmonary tuberculosis require longer duration The commonest form of candidiasis in a kidney
of treatment. Treatment of active MTB in the transplant recipient is that of mucosal involve-
post-transplant setting is challenging in view of ment leading to oral thrush, oesophageal candidi-
the interaction of anti-tubercular and immuno- asis and candidal vaginitis. Severe forms can
suppressive medications, in particular Rifampicin, present as candidemia with hematogenous spread
which is a potent enzyme inducer and it is very to various organs. Candida albicans is the most
difficult to achieve adequate tacrolimus levels common cause of invasive candidiasis, followed
with concomitant Rifampicin treatment. by non-albicans such as glabrata and krusei.
Therefore, to treat active MTB post-transplant, Pulmonary aspergillosis is the most common pre-
often non-Rifampicin-based regimen would be sentation of invasive aspergillosis in kidney trans-
required which may make the treatment less plant recipients. Aspergillus fumigatus and flavus
effective. are the commonest causes, followed by rare types
like terreus. The patient with pulmonary aspergil-
losis presents with cough, dyspnoea, low-grade
ungal Infections in Kidney
F fever and haemoptysis. Due to its angio-invasive
Transplant Recipients nature, it can lead to organ infarction and dissemi-
nation to other organ systems. Aspergillosis of
Fungal infections are a serious infectious compli- urinary tract and vascular anastomotic site can
cation of kidney transplant recipients in certain happen rarely due to infected graft-associated
parts of the world where environmental factors transmission. Cryptococcosis is another common
contribute significantly in addition to host fac- fungal infection in kidney transplant recipients.
tors. Some of the fungal infections such as histo- Most common organism is Cryptococcus neofor-
plasmosis, blastomycosis, coccidioidomycosis, mans, but cases with C. gattii have been increas-
para-coccidioidomycosis are endemic in some ingly reported now. Presentation is usually 6
geographical areas of the world, and some are months after transplantation. The most common
opportunistic fungal infections more widespread site of presentation is central nervous system
all over the world, affecting immunocompro- (CNS). Cryptococcal meningitis presents with
mised hosts (candidiasis, aspergillosis, crypto- unexplained headache, fever and altered con-
coccosis, mucormycosis). In most series, sciousness level. Unexplained skin involvement
candidiasis is the most common invasive fungal can be another form of presentation.
Mucormycosis is an angio-invasive fungal infec- levels due to the inhibition of CYP3A4 cyto-
tion. Rhino-paranasal sinus-cerebral mucormyco- chrome isoenzyme. Tacrolimus level needs to be
sis is the most common presentation. Other forms monitored closely in these patients and a dose
including pulmonary, cutaneous, gastrointestinal reduction is often needed. In severe, invasive fun-
tract (GIT), graft kidney and disseminated dis- gal infections and fungaemia, drugs such as caspo-
ease. Due to the angio-invasive nature the dis- fungin (An Echinocandin) or Anidulafungin and
semination of fungus is rapid with high fatality liposomal amphotericin B would be needed along
rate reaching up to 75% despite appropriate and with drastic reductions or complete withdrawal of
timely surgical and medical treatment. immunosuppression. Cryptococcal meningitis is
Endemic mycosis has varied presentation. treated with liposomal amphotericin B plus flucy-
Histoplasmosis presents as fever, weight loss, tosine followed by prolonged periods of oral fluco-
pancytopenia, and lymphadenopathy due to nazole. Invasive mucormycosis will need treatment
lympho- reticular system involvement. with IV liposomal amphotericin B with posacon-
Disseminated infection with CNS involvement azole as stepdown treatment if there is response.
may be seen. Blastomycosis can involve pulmo- The prognosis of kidney transplant patients
nary system causing acute respiratory distress with invasive fungal infections remains poor and
syndrome (ARDS) and can also involve muscu- therefore, measures to prevent or minimise the
loskeletal system. Coccidioidomycosis may have risk of these infections are of paramount
similar presentations. importance.
Diagnosis and Management OVID-19 Infection and Kidney

C
of Fungal Infections Transplant Recipients
A high index of suspicion is important in diag- COVID-19, a respiratory disease caused by the
nosing fungal infections, as the symptoms might coronavirus SARS-CoV-2 was declared a global
be non-specific. Main principles of management pandemic in March 2020. The disease has
are reducing immunosuppression, removing/ affected millions of people globally with a case
replacing intravenous cannulae and urinary cath- fatality ratio of 25–30% in hospitalised kidney
eter. A combination of appropriate fungal stains transplant patients infected with the virus. The
and culture on suitable body fluids, molecular current strategies to combat the virus include
diagnostic methods and imaging would be needed societal measures to minimise the risk of aerosol
to make a diagnosis. Always work closely with transmission, hand hygiene, wearing masks in
microbiology department to facilitate appropriate closed spaces and vaccination. The management
investigations. A blood 1,3 beta-D-glucan is use- options available at the time of this writing in
ful as a screening test for invasive fungal infec- March 2021 are supportive measures, respiratory
tions, but it is non-specific. Cryptococcal support, reduction in immunosuppression (reduc-
meningitis is diagnosed by CSF examination by tion or withdrawal of mycophenolate mofetil
India ink stain and gram stain. Cryptococcal anti- depending on disease severity, continuation of
gen detection in CSF has excellent sensitivity and tacrolimus and steroids in most of the cases,
specificity and it is one of the best tests for a rapid dexamethasone in suitable patients as per
diagnosis. PCR to detect fungal nucleic acid RECOVERY trial evidence, Remdesivir as per
improves the diagnostic yield. local guidelines, Tocilizumab in severe cases as
Treatment depends upon the nature of the fun- per local and national guidelines along with par-
gus and severity of the illness. Oral Candidiasis ticipation in clinical trials testing new therapies.
may just require nystatin suspension whereas AKI is common in kidney transplant patients
Esophageal candidiasis would need Fluconazole with COVID-19 but most of the patients do
which interacts with Tacrolimus increasing the recover their graft function. The reduction in
immunosuppression may result in rejection of the Tacrolimus to Cyclosporine A to improve glycae-

kidney but this is not common in our experience. mic status is not recommended.
Management of diabetes in the longer-term
post-transplantation (whether new onset or not)
Other Common Infections follows similar strategies to those of the general
and Vaccinations Post-Transplant population that include diet and lifestyle advice
to enable weight loss and drugs. Late steroid
In addition to common bacterial chest infections withdrawal or an attempt to run low tacrolimus
and urinary tract infections, Infections with levels to achieve better glycemic control are not
Herpes family of viruses can occur post- recommended as these measures often result in
transplant causing genital herpes infections and acute or chronic rejection with reductions in
shingles. Treatment is with Aciclovir or graft survival or further increase in steroid expo-
Valaciclovir. It is important to screen waitlisted sure due to treatment of rejection episodes. To
patients for Varicella-Zoster (VZV) antibodies treat diabetes post transplantation, all the usual
and immunise with VZV vaccine in those who oral agents can be used (Metformin remains a
are antibody negative. As this is a live vaccine, it drug of choice), following the usual modifica-
must be given to patients before transplantation. tions to account for kidney transplant function.
It is recommended that all kidney transplant Insulin can be used as needed. The SGLT2 inhib-
patients receive annual influenza vaccine and itors are likely to be of significant renal and car-
pneumococcal vaccine once every 5 years. It is diovascular benefit for overweight kidney
also recommended that transplant patients receive transplant recipients, similar to their beneficial
SARS-CoV-2 vaccine to protect against effects observed in non-transplant population
Covid-19. Live vaccines should be avoided in but these drugs haven’t been systematically
kidney transplant recipients, and they should tested in kidney transplant patients. Concerns
only have inactivated (killed) vaccines. are potential increased risk of infections, in par-
ticular genitourinary infections in women, risk
of dehydration leading to volume depletion and
Post-Transplant Diabetes AKI when used in association with ACEI/ARBs.
It is unlikely that the latter would be a significant
New-onset diabetes after transplantation clinical issue.
(NODAT) or Post Transplant Diabetes Mellitus
(PTDM) occurs in 5–20% patients following kid-
ney transplantation, depending on pre-transplant Acute and Chronic Rejection
patient characteristics, post-transplant weight
gain and the immunosuppressive regime. The Acute or chronic alloimmune injury results in
immunosuppressive drugs Tacrolimus and corti- rejection of the allograft. This may be acute,
costeroids both increase the risk of diabetes post chronic, acute on chronic, cellular (T-cell driven),
transplantation. Early steroid withdrawal results antibody-mediated or in many cases, mixed
in low incidence of PTDM, and this should be T-cell and antibody-mediated rejections.
considered in suitable recipients with appropriate Hyperacute rejection, where severe vascular
immunological risk stratification. The presence rejection occurs driven by preformed donor spe-
of PTDM is associated with an increased risk of cific anti-HLA antibodies is almost an unknown
graft loss, cardiovascular disease and mortality. entity in the modern era of kidney transplantation
Although tacrolimus is associated with higher where recipients are screened carefully for donor
risk of diabetes compared to cyclosporine A, specific anti-HLA antibodies with Luminex tech-
given the better tolerability and lower risk of nology along with crossmatch techniques that
rejection with tacrolimus, routine switch from incorporate flowcytometry and CDC methods.
• Acute rejection typically occurs within and vessel wall), C4D staining in peritubular cap-
3–4 months post-transplantation but it can illaries, thrombotic microangiopathy and pres-
occur anytime. Steroid resistant rejections and ence of donor specific anti HLA antibodies. C4D
recurrent episodes of rejections confer poor negative AMR is now well-recognised.
prognosis. Usually, there are no clinical fea- It must be emphasised that cellular (T-cell
tures associated with transplant rejection driven), and Antibody mediated rejections
except for severe cases where there could be (AMRs) often occur together.
graft tenderness. Additional categories belong to ‘chronic rejec-
• Suspect rejection in following situations: An tion’ and both chronic antibody mediated rejec-
increase in serum creatinine of ≥20–25% tion (transplant glomerulopathy, multilayering of
from baseline OR a serum creatinine that is peritubular capillary basement membrane seen on
stable but higher than expected following electron microscopy, C4D staining in PTCs, arte-
transplantation OR a creatinine that stops rial intimal fibrosis) and chronic T cell mediated
decreasing further following initial decline rejection (Chronic TCMR, characterised by vary-
post- transplant OR delayed graft function ing degrees of tubular atrophy/interstitial fibrosis
with dialysis dependence post- transplant. (IFTA) along with interstitial inflammation,
chronic allograft vasculopathy- arterial intimal
Rejection can only be definitely diagnosed by fibrosis with mononuclear inflammatory cells) are
graft biopsy and histopathology. The Banff grading now recognised and these are important causes of
system is updated and modified regularly to include chronic allograft dysfunction and eventually, graft
histological patterns, mechanisms of rejection, failure. Chronic rejection, in particular chronic
acute Vs chronic rejection, activity and chronicity AMR/transplant glomerulopathy is usually asso-
index within a given histological sample. The com- ciated with significant proteinuria and progres-
monly known ‘acute cellular rejection’ is a T-cell sively increasing proteinuria of >1 g/day is an
mediated process characterised by interstitial lym- indication to perform a kidney biopsy to diagnose
phocytic infiltrates and infiltration of tubular epithe- chronic AMR or recurrent glomerular disease.
lium by lymphocytes (tubulitis) severity of which is Late rejection episodes (occurring more than
graded depending upon the percentage of cortex 6 months after transplantation) are often due to
covered by cellular infiltrates and number of lym- inadequate immunosuppression either due to poor
phocytes per cross section of tubule (Type IA and adherence and non-compliance with immunosup-
1B rejection in 1997 Banff grading; Category 4, pressive medications or due to inappropriate reduc-
TCMR 1A and 1B in 2017 Banff grading). If blood tions in tacrolimus dose aiming for low levels to
vessels are involved by lymphocytic infiltration it minimise CNI toxicity or inappropriate late steroid
would be classed as more severe ‘vascular’ rejec- withdrawals. The tacrolimus levels should be
tion graded based on the extent of intimal involve- maintained between 5 and 7 ng/mL (with excep-
ment or transmural involvement (Type IIA, B and tion of PTLD and other malignancies where lower
III in 1997 Banff grading; Category 4, TCMR IIA, levels may be desirable) long term to minimise the
IIB and III in 2017 Banff Grading). These catego- risk of de-novo DSA formation, reduce the risk of
ries are T cell mediated rejection that often respond late acute and chronic rejections. Table 23.2 sum-
to IV methylprednisolone but cases with vascular marises the differences between acute T-cell medi-
involvement (in particular, grade IIB and III) often ated (cellular) rejection (ACR/Acute TCMR) and
require Anti-thymocyte globulin (ATG). acute antibody-mediated rejection (AMR).
The second main category of rejection is Maintenance of adequate immunosuppres-
acute/active antibody mediated rejection (AMR, sion, particularly maintaining tacrolimus levels
category 2 in 2017 Banff grading system) which in range most of the time reduce the risk of
requires demonstration of microvascular inflam- chronic TCMR as well as chronic AMR. While
mation in peritubular capillaries (PTC) or glom- keeping patients on triple immunosuppression
erulus (neutrophilic infiltrates in endothelium (Tacrolimus, mycophenolate mofetil and pred-
AL GRAWANY
Table 23.2 Differences between acute T cell mediated (cellular) rejection (ACR/Acute TCMR) and acute antibody-
mediated rejection (AMR) and management options
ACR (Acute TCMR) Acute AMR
Interstitial lymphocytic
• Present Absent (Can occur when there is
infiltration, Tubulitis concomitant TCMR)
Vascular mononuclear
• Present Absent
inflammation, fibrinoid
necrosis
Donor-specific antibody
• Absent Present
in serum
Neutrophilic infiltrates in
• Absent Present
glomerular and
peritubular capillaries
with or without
microvascular thrombosis
(TMA), histological and
electronmicroscopic
evidence of endothelial
injury
C4d staining in
• Absent Present
peritubular capillaries
(PTC)
Absent Present
• Primary therapy Pulse methylprednisolone, rabbit Plasmapheresis (PEx) (Usually 5
anti-thymocyte globulin (ATG) (for sessions), intravenous immunoglobulin,
vascular T-cell rejection, grade IIB and pulse steroids. ATG if concomitant
above), increase in baseline severe T cell mediated cellular/vascular
immunosuppression, consider assessing rejection. Optimise Tacrolimus levels.
mycophenolic acid exposure and adjust Consider assessing mycophenolic acid
the dose. exposure and adjust the dose.
Eculizumab is an option in severe cases
of AMR. Rituximab has been used with
limited evidence and the efficacy
remains unclear. IvIg and ATG should be
given post-PEx.
nisolone) long term seems like best option to with urinary cell transcriptomics, urinary bio-
reduce the risk of chronic rejection, there is no marker (free and exosomal proteins, miRNA)
evidence that this is the case compared to long panels diagnostic of rejection, circulating cell
term dual immunosuppression (Tacrolimus, free donor DNA to detect allograft damage and
mycophenolate mofetil OR tacrolimus, predniso- rejection in early stages, routine molecular
lone; which is our usual practice for majority of analysis of biopsy specimen, Safe CNI free
our standard risk transplant recipients) and long- regimen with co-stimulatory blockade, proto-
term triple immunosuppression is likely to be cols designed to develop transplant tolerance
associated with higher rate of infections and and evidence base for utilisation of DSAs as
malignancies. biomarkers to optimise long term outcomes. In
The optimal immunosuppression long-term addition to these, there is a need for good qual-
remains unclear and it should be individualised ity clinical research to identify optimal long
as much as possible taking in to account the term immunosuppressive regimes, treatment
immunological (rejection) risk, infection risk, protocols that are effective and safe for acute
cancer risk and patient preferences to achieve AMR and chronic rejection (cAMR and
best long-term outcomes. cTCMR), treatments that work for recurrent
Some of the new developments in this field glomerular diseases, in particular, recurrent
include: non-invasive diagnosis of rejection IgAN.
Calcineurin Inhibitor these drugs may not be well tolerated which often
Nephrotoxicity leads to switching back to tacrolimus but in those
who tolerate these drugs, GFR tends to stabilise
Whilst the CNIs ciclosporin and tacrolimus revolu- and improve. Usual guideline for switching is:
tionized the world of solid organ transplantation by eGFR >35 mL/min and proteinuria <1 g/day
prolonging graft survival, they are potentially neph- (lesser the better). Hyperlipedemia, worsening
rotoxic agents. CNIs can lead to both acute kidney proteinuria and thrombocytopenia are potential
injury (AKI), which is due to dose dependent side effects of mTOR inhibitors. These drugs
reversible vasoconstriction of glomerular afferent should be stopped 2 weeks before any elective
arterioles leading to drop in GFR and chronic toxic- surgery and patient switched back to tacrolimus
ity (vasculopathy and tubulointerstitial fibrosis) as wound healing can be markedly impaired if
which is largely irreversible. However, as described operations are done while on mTOR inhibitors.
in previous section on rejection, very similar histo-
pathological changes of vascular sclerosis and tubu-
lointerstitial fibrosis do occur secondary to chronic Delayed Graft Function (DGF)
TCMR and chronic AMR and it can be quite diffi-
cult to distinguish between these entities. Electron DGF refers to poor transplant kidney function in
microscopic features of PTC multilayering, intersti- the immediate post-transplantation period and
tial inflammation and C4D positivity are suggestive can be caused by donor events before or during
of chronic rejection whereas striped interstitial retrieval that leads to ischaemic kidney injury,
fibrosis without inflammatory infiltrates is sugges- older donor age (and other extended criteria
tive of chronic CNI toxicity. donor), DCD (donation after cardiac death) kid-
Acute CNI nephrotoxicity is common is early neys, warm ischaemia or trauma to blood vessels
post- transplant period and rise in creatinine due at the time of organ retrieval, prolonged cold
to high tacrolimus levels usually settles down ischaemia or perioperative hypotension. The
within 48h-72h of dose reduction and achieving most common definition of DGF is the need for
therapeutic target levels. If the creatinine levels dialysis within one week of transplantation. The
remain high with tacrolimus dose reduction, a management is to run tacrolimus levels slightly
biopsy should be performed. low, transplant kidney biopsy to exclude rejection
Thrombotic microangiopathy can be a mani- after making sure perfusion of the kidney is fine
festation of CNIs toxicity which can occur at with patent renal vein and support the patient
any dose or plasma level. Treatment often is with dialysis and optimal fluid balance while
withdrawal of CNI and replacing CNI with waiting for the kidney to open up.
mTOR inhibitor such as sirolimus/everolimus
or maintaining on mycophenolate mofetil/pred-
nisolone combination. Belatacept is another Chronic Allograft Failure
option in these patients to keep them CNI free.
CNIs can lead to hyperkalaemia with a mild Over a period of years, the transplant kidney func-
acidosis due to type IV renal tubular acidosis. tion declines leading to progressive CKD and even-
Other electrolyte disturbance due to CNI toxic- tually graft failure requiring kidney replacement
ity include hypomagnesemia and hypophospha- therapy. There is often combination of factors that
taemia although the latter is more often likely lead to chronic inflammation and fibrosis in the
due to parathormone induced phosphate loss in transplant kidney leading to graft failure. These
patients with underlying secondary or tertiary include, chronic allograft nephropathy (A term used
hyperparathyroidism before transplantation. to describe immunological and non-immunological
Chronic allograft dysfunction attributed to causes of graft damage), chronic rejection (cAMR
CNI induced graft fibrosis can be managed by and cTCMR), hypertension and vascular disease
switching to mTOR inhibitors. Unfortunately, with or without diabetes mellitus, recurrent glomer-
ular disease, recurrent episodes of acute rejection, layering on electron microscopy and positive
recurrent episodes of urinary tract infections with or donor-specific HLA antibodies in serum favour
without obstructive uropathy in transplant kidney, the diagnosis of cAMR, whereas absence of these
calcineurin inhibitor (CNI) toxicity and BKV features and systemic complement abnormalities
nephropathy. It is important to focus on and opti- favour the diagnosis of recurrent MCGN. Primary
mise management of cardiovascular risk factors FSGS can recur in early post-transplant period
including appropriate management of hyperlipidae- with severe nephrotic range proteinuria and graft
mia, hypertension and diabetes along with smoking dysfunction or recur with a more indolent course.
cessation and weight management. The optimal Management of aggressive recurrent FSGS
management of these non-immunological risk fac- includes plasmapheresis (usually 5 sessions) fol-
tors play a vital role in long-term patient and graft lowed by Rituximab. These therapeutic measures
survival. Chronic rejection and CNI toxicity have may need repeating at regular intervals depend-
been discussed in previous section. ing upon clinical response and tolerability.
Recurrent glomerular disease is an important Recurrent IgA nephropathy is common after kid-
cause of graft dysfunction and failure. Primary ney transplantation with most of the transplant
focal segmental glomerulosclerosis (FSGS), kidneys demonstrating mesangial IgA deposits
mesangiocapillary, MCGN (membranoprolifera- 3–5 years post-transplant usually resulting in
tive, MPGN) and IgA nephropathy are the pri- chronic allograft dysfunction but more aggres-
mary glomerulonephritidis most likely to recur in sive recurrences with necrotising and crescentic
transplant kidney. Other glomerular disorders glomerulonephritis is also known. Unfortunately,
such as membranous glomerulonephritis can there is no specific treatment for this common
recur in the transplant kidney but this is not a recurrent disease in transplant kidney.
common clinical problem. ANCA positive vascu-
litis and anti-glomerular basement membrane
(GBM) disease very rarely recur in the transplant Cancer
kidney. De-novo anti-GBM disease has been
reported in patients with Alport’s syndrome Cancer rates are higher in transplant recipients
receiving a kidney from a donor with no Alport compared to general population. This is particu-
like collagen abnormalities. De-novo glomerulo- larly true for skin cancers and cancers driven by
nephritis has been reported but these are rare. viral proliferation such as PTLD (EBV), Kaposi’s
Thrombotic microangiopathy (renal limited, sys- sarcoma (human herpes virus 8, HHV8) and cer-
temic or both) can affect the transplant kidney in vical cancer (human papilloma virus). There is a
acute, subacute and chronic forms. Usually this is modest increased risk of other cancers such as
due to CNI toxicity (non-dose dependent), acute lung and gastrointestinal cancers while there seem
or chronic active AMR or combination of the to be no increased risk of other common cancers
two. Atypical haemolytic uraemic syndrome such as breast and prostate malignancies.
(aHUS) can recur in early post-transplant period The higher levels of immunosuppressive bur-
resulting in systemic thrombotic microangiopa- den over a period of time increases the risk of
thy, systemic complement abnormalities, glo- cancers. The mTOR inhibitors have been associ-
merular microthrombi and graft dysfunction ated with lower rates of cancer but higher inci-
which can lead to rapid graft loss. The manage- dence of side effects and poor tolerance have
ment consists of plasmapheresis and consider- prevented their widespread use. However, in
ation of Eculizumab. Recurrent MCGN is often selected cases of cancers, for eg, recurrent squa-
difficult to distinguish from chronic antibody mous cell skin cancers, a switch to sirolimus or
mediated rejection (cAMR) as glomerular histo- everolimus should be considered. The manage-
logical pattern can be similar in these conditions. ment of cancers consists of running immuno-
Positive C4D staining in peritubular capillaries, suppression as low as possible along with
peritubular capillary basement membrane multi- specific treatment for a given malignancy.
A. Background history of Diabetes Mellitus

Practice Point 4 and use of ATG and Tacrolimus are risk
• Kidney Transplantation is the best form factors for development of tuberculosis
of long -term kidney replacement ther- in him
apy in suitable recipients B. The source of infection could be donor
• Both living and deceased donor trans- derived, endogenous reactivation of dis-
plants offer excellent short to medium ease or a de-novo infection
term results with room for improvement C. Treatment should include initiation phase
in long term outcomes. Compared to of 2 months of HRZE followed by
patients remaining on dialysis, kidney 10 months of continuation phase of HR
transplant patients have lower mortality D. Rifampicin based regime should be
and better quality of life avoided in view of its interaction with
• Recipient work-up for kidney transplan- tacrolimus
tation includes surgical, immunological E. Rifampicin based regime would be nec-
and non-immunological assessments to essary, in spite of its interaction with
optimise outcomes and minimise tacrolimus
complications Answer – D This patient has CNS tuber-
• Surgical complications are rare and culosis. In cases of CNS tuberculosis, a pro-
include arterial/venous thrombosis, longed maintenance phase of at least
bleeding, ureteric leak, wound infec- 10 months will be required, and the rifampi-
tions and lymphocele cin should be included in the treatment
• Medical complications include acute regime, since a rifampicin sparing regime
and chronic rejection, higher rate of typi- would not be sufficient in severe cases like
cal and atypical infections and malig- this. The dose of tacrolimus will need adjust-
nancies secondary to immunosuppression ment (a higher dose will be needed), in view
and post-transplant diabetes mellitus of the interaction with rifampicin
2. A 64-year-old man presents to the Transplant
service five months after his migration from
Bangladesh to London, UK. He has a history
Questions of CKD Stage 5 and hypertension. He was
placed on the waiting list for a kidney
1. A 45-year-old man with Type 2 Diabetes transplant
Mellitus, hypertension and CKD Stage G5 All of the following are true except:
on maintenance haemodialysis, received a A. He should be screened for latent tubercu-
living donor kidney transplant, with his wife losis as he is coming from a high endemic
as a donor. The induction consisted of thy- region or given Isoniazid prophylaxis
moglobulin (ATG), with maintenance immu- post- transplant
nosuppression of Tacrolimus, MMF and B. A tuberculin skin test will be more sensi-
prednisone. Seven months post-transplant, tive and specific compared to interferon
he developed a headache and fever. On gamma release assay to detect latent
examination, there was neck stiffness. A CT tuberculosis in him
brain scan showed a granulomatous lesion. C. In case of a positive test for latent tuber-
Lumbar puncture revealed 70 cells/high culosis, he should be treated for the same
power field, with 90% lymphocytes, glucose while he is on the waitlist
50 mg/dL (blood glucose value was 100 mg/ D. The treatment course may be interrupted
dL), protein 65 mg/dL, and increased ADA and continued post-transplant in case the
(Adenosine deaminase) (25 IU/L) patient receives a deceased donor kidney
All of the following are true except: while on the waitlist
Answer – B An interferon gamma release assay an important component of overall manage-

will be more sensitive and specific in this ment. Prognosis is poor
patient than the tuberculin skin test. It will 4. Ms. YK, a 46-year-old female presented with a
also help in differentiating anergy from a true history of headache and low-grade fever for
negative test one week. She had known hypertension, hypo-
In the UK, and in other developed parts thyroidism and ESKD. She underwent an unre-
of the world, the usual practice is to com- lated living donor kidney transplant eleven
plete the treatment for TB before trans- months previously; her husband was the kidney
plantation, especially when a donor. Her induction regimen was thymoglob-
Rifampicin-based regime is used to treat ulin (ATG); her maintenance immunosuppres-
latent tuberculosis. In parts of the world sion consisted of Tacrolimus, MMF and
where transplantation is highly desirable prednisone. On examination, she had neck
compared to keeping the patient on dialy- stiffness. Her CT brain scan was normal. A
sis, option D may be used—and is there- lumbar puncture was performed, and her CSF
fore not the correct answer analysis showed 42 cells, 70% lymphocytes,
3. A 55-year-old man, with known Type 2 glucose of 50 mg/dL and protein of 98 mg/
Diabetes Mellitus, hypertension and dL. CSF staining for India ink was positive, as
ESKD. He underwent a deceased donor kid- was her cryptococcal antigen stain
ney transplant one year ago. Basiliximab was All of the following are true except:
used as an induction agent, and he was on A. Cryptococcal infections are commoner in
maintenance triple immunosuppression of kidney transplant recipients and may
Tacrolimus, MMF and prednisone. His blood clinically mimic tuberculosis
glucose control has been poor lately. He pre- B. Presentation is usually six months
sented with headache of 10 days’ duration. On post-transplantation
examination, he had tenderness over his bilat- C. The most commonly affected organ is the
eral maxillary sinuses. An ENT examination lung
showed a blackish material, which on histo- D. IV liposomal amphotericin B and flucyto-
pathological examination revealed broad non- sine are used in treatment in the induction
septate hyphae, suggestive of mucormycosis phase, followed by fluconazole in the
All of the following statements are true consolidation and maintenance phases
except: Answer – C The most common site of involve-
A. IV liposomal amphotericin B should be ment in cryptococcal infection is central ner-
started immediately, and MMF should be vous system
stopped 5. A 55-year-old female with a functioning
B. Immunosuppressive medications and deceased donor kidney was seen in the kid-
poorly controlled Diabetes Mellitus are ney transplant follow-up clinic. Her serum
important risk factors for mucormycosis creatinine levels increased from 90 μmol/L
C. Surgery has no role in the management to 170 μmol/L between days 30 and 40 post
and medical management with IV liposo- transplantation. Her blood tacrolimus levels
mal amphotericin B, followed by were high between 18 and 20 ng/mL between
posaconazole gives a good cure rate days 30 and 40. He had a kidney biopsy
D. Mucormycosis is an angio-invasive dis- What are the features suggestive of tacro-
ease, with high rates of mortality limus toxicity on kidney biopsy?
Answer – C Extensive debridement to remove A. Glomerular mesangial expansion
the infected material is an important step in B. Lymphocytic infiltrates in the intersti-
containing the infection. Amphotericin B tium
and posaconazole are used to treat the infec- C. Lymphocytic infiltration into blood
tion and reduction of immunosuppression is vessel
D. Vacuolation of tubular cells What is the most likely finding on the kid-
E. Oedema in the interstitium ney biopsy?
Answer – D A. Glomerular mesangial expansion
6. A 65-year-old female developed a tender B. Lymphocytic infiltrates in the interstitium
swelling over the right iliac fossa lateral to C. Striped fibrosis of the interstitium
the scar for her deceased donor kidney trans- D. Vacuolation of tubular cells
plantation five days prior. Her serum creati- E. Oedema in the interstitium
nine improved from 465 μmol/L to Answer B
260 μmol/L. The collection on ultrasound 9. A 43-year-old female patient with BMI of
which caused the swelling was drained with 38 kg/m2 on peritoneal dialysis with a history
ultrasound guidance. The drain fluid was yel- of end stage kidney disease secondary to adult
low had a creatinine of 270 μmol/L polycystic kidney disease received her first live
What is the most likely cause of the donor kidney transplant from a 58-year-old
swelling? genetically unrelated, ABO compatible donor.
A. Haemorrhage The donor kidney had a small lower polar
B. Infection artery, in addition to a main renal artery, which
C. Lymphocele was anastomosed separately. She had an other-
D. Lipoma wise uneventful transplant surgery, with imme-
E. Urine leak diate allograft function on the table. She
Answer – C continued to have a high drain output from
7. A 45-year-old female with a functioning sec- immediately post-operatively, which has failed
ond deceased donor kidney transplant was to settle
seen in the kidney transplant follow-up clinic. What is the most important next
Her serum creatinine levels had increased investigation?
from 100 μmol/L to 150 μmol/L between days A. Transplant kidney ultrasound
20 and 25 post transplantation. Her blood B. Measure drain fluid creatinine
tacrolimus levels were as expected, between 8 C. Drain fluid microscopy, culture and
and 10 ng/mL. She had a kidney transplant sensitivities
biopsy. Both she and her donor were negative D. Repeat haemoglobin
for CMV before transplantation E. Immediate serum urea and electrolytes
What is the most likely cause of her acute measurement
kidney injury? Answer – B The above case is a common pre-
A. Acute rejection sentation after renal transplant. Iatrogenic
B. Acute tubular necrosis missed peritoneal membrane injury or injury
C. Tacrolimus toxicity to a native renal cyst can confuse the com-
D. CMV infection mon differential diagnosis of urinary leak or
E. BK virus infection lymphocele. Smaller lower polar artery, if
Answer – A thrombosed increased the risk of distal ure-
8. A 45-year-old female with a functioning sec- teric necrosis resulting in urinary leak. High
ond deceased donor kidney transplant, was BMI is a risk factor for lymphocele. The key
seen in the kidney transplant follow-up clinic. initial investigation here is creatinine level in
Her serum creatinine levels increased from drain fluid to establish diagnosis of urinary
100 μmol/L to 150 μmol/L between days 20 leak or lymphocele
and 25 post transplantation. Her blood tacro- 10. A 63-years old male patient with history of
limus levels were as expected between 8 and end stage kidney disease secondary to dia-
10 ng/mL. She had a kidney transplant biopsy. betic nephropathy received a kidney from a
Both she and her donor were negative for 69-years old deceased donor after circulatory
CMV before transplantation arrest (DCD donor). After initial period of
delayed graft function, he had good kidney References

allograft function. He had double J ureteric
stent removal at 6 weeks, following which 1. Mundy AR, Podesta ML, Bewick M, Rudge CJ, Ellis
FG. The urological complications of 1000 renal trans-
his creatinine started to go up with dropping plants. Br J Urol. 1981;53(5):397–402. https://doi.
urine output org/10.1111/j.1464-410x.1981.tb03216.x.
What is the most likely cause? 2. Leapman SB, Vidne BA, Butt KM, Kountz
A. Ureteric stricture SL. Elective and emergency surgery in renal transplant
patients. Ann Surg. 1976;183(3):266–70. https://doi.
B. Acute Cellular Rejection (ACR) org/10.1097/00000658-197603000-00009.
C. Antibody Mediated Rejection (AMR) 3. Ayvazoglu Soy EH, Akdur A, Kirnap M, Boyvat F,
D. Transplant urinary infection Moray G, Haberal M. Vascular complications after
E. Fluid depletion renal transplant: a single-center experience. Exp Clin
Transplant. 2017;15(Suppl 1):79–83. https://doi.
Answer – A This is most likely to be a case org/10.6002/ect.mesot2016.O65.
of a lower ureteric stricture due to ischaemia, 4. Eufrásio P, Parada B, Moreira P, Nunes P, Bollini S,
that has manifest after ureteric stent removal Figueiredo A, Mota A. Surgical complications in 2000
renal transplants. Transplant Proc. 2011;43(1):142–4.
https://doi.org/10.1016/j.transproceed.2010.12.009.
Test your learning and check your understand- 5. Kocak T, Nane I, Ander H, Ziylan O, Oktar T, Ozsoy
ing of this book’s contents: use the “Springer C. Urological and surgical complications in 362 con-
Nature Flashcards” app to access questions using secutive living related donor kidney trans- plantations.
https://sn.pub/cz9Cok. To use the app, please fol- Urol Int. 2004;72:252–6.
low the instructions in Chap. 1.
An Approach to Obstetric
Nephrology
24
Anita Banerjee , Serene Thain,
and Brenda Sequeira Dmello
Clinical Scenario 1 Introduction

A 32 year old woman with Type I diabetic for the
past 16 years presents to the preconception clinic. Physiological adaptations of the kidney in preg-
She is planning her 4th pregnancy. Her serum nancy are marked by significant volume expan-
creatinine is 122 μmol/L and her urine sion and vasodilation. Renal plasma flow
protein:creatinine ratio (uPCR) is 142 mg/mmol. increases up to 80% and the glomerular filtration
Her HbA1c is 88mmol/mol. She is on basal bolus rate increases by 50% compared with non-
insulin: Novorapid and Levemir. pregnant levels. The resulting decrease in serum
creatinine levels lead to an average creatinine in
• What pre-pregnancy counselling would you pregnancy of 53 mmol/L [1, 2]. Serum creatinine
offer her? levels should therefore not be interpreted in the
• What would be the treatment target for her same way as in non-pregnant women. Similarly,
blood pressure in pregnancy? because of these haemodynamic changes, esti-
• How would you recognize the development of mated glomerular filtration rate (eGFR) measure-
superimposed pre-eclampsia? ments, widely used in non-pregnant adults have
not hitherto been validated in pregnant women.
Aside from acute kidney injury in pregnancy,
women can also enter pregnancy with pre-
existing chronic kidney disease (CKD). The pres-
ence of CKD increases the risk of adverse
obstetric, maternal and perinatal outcomes such
as preterm birth, foetal growth restriction, hyper-
A. Banerjee (*) tensive disorders of pregnancy such as gesta-
Women’s Services, Guy’s and St Thomas’ Hospitals tional hypertension or pre-eclampsia, and
NHS Foundation Trust, London, UK
e-mail: anita.banerjee@gstt.nhs.uk stillbirth. Pregnancy can potentially worsen pre-
existing CKD, and lead to further deterioration in
S. Thain
Department of Maternal & Fetal Medicine, KK kidney function, that may or not recover fully
Women’s and Children’s Hospital, back to baseline in the postpartum period.
Singapore, Singapore This chapter will aim to discuss the management
e-mail: serene.thain.p.t@singhealth.com.sg of CKD in pregnancy, including transplant recipi-
B. S. Dmello ents, as well as the diagnostic work-up and differen-
Medical College, Aga Khan University, tials for acute kidney injury (AKI) in pregnancy.
Dar es Salaam, United Republic of Tanzania
https://doi.org/10.1007/978-3-031-09131-5_24
490 A. Banerjee et al.
Chronic Kidney Disease include that of disease aetiology, severity of the dis-
ease, rate of decline outside of pregnancy and pre-
CKD affects 0.1 to 3% of all pregnancies. The vious obstetric history. An additional factor
prevalence of CKD is rising, likely contributed by associated with adverse pregnancy outcomes inde-
the changing obstetric landscape worldwide with pendent of kidney disease is that of superimposed
increasing number of advanced maternal age pre-
eclampsia (PET). The responsibility of the
pregnancies, increasing incidence of diabetes healthcare professional is to facilitate an autono-
mellitus and obesity. Individualised pre-pregnancy mous and informed decision-making process.
counselling and optimisation for every single With regard to the optimal timing for concep-
woman of childbearing age with CKD is an tion, the aim would be to strive for quiescence and
important aspect not to be forgotten. stability of kidney disease before trying to conceive.
Traditionally, many nephrologists have advised Entering a pregnancy with kidney disease that has
women with CKD to avoid pregnancy. However, been quiescent for six months prior to conception
this paternalistic approach can and should no lon- has been shown to improve outcomes. For women
ger hold true. All women of childbearing age with mild CKD, the risk of significant loss of kid-
should be involved in shared decision-making with ney function at the end of pregnancy is possible,
health professionals regarding future planning for though not likely. For those with more advanced
pregnancies. The risks of pregnancy and progres- CKD however, the potential for loss of kidney func-
sion of maternal CKD need to be considered. Pre- tion must not underestimated, and women should
existing hypertension, proteinuria and kidney be counselled appropriately, and implications dis-
impairment are associated with an increased risk cussed before embarking on pregnancy.
for adverse pregnancy outcomes in women with The common causes of CKD in women of
CKD. Other factors contributing to outcomes childbearing age are described in Table 24.1,
Table 24.1 Risks of various causes of chronic kidney disease on pregnancy and pregnancy-specific aims and targets
Type of kidney Pregnancy-specific aims and
disease targets CKD-specific obstetric risks
Adult polycystic • Intensify targets for blood • Pre-existing hypertension is a risk factor for
kidney disease pressure control adverse pregnancy outcomes, others include
(APKD) • Infection (pyelonephritis)
• Kidney calculi
• Kidney cyst complications (rupture, haemorrhage)
IgA nephropathy • Intensify targets for blood • Pre-existing hypertension is a risk factor for
(IgAN) pressure control adverse pregnancy outcomes
• Presence of >1 g of protein a day is associated
with an increased risk of loss of residual
function, independent of pregnancy
Diabetic • Intensify targets for blood • Pre-existing hypertension is a risk factor for
nephropathy pressure control and glucose adverse pregnancy outcomes
(DN) pre-pregnancy and throughout • Risk of acceleration of kidney disease
pregnancy • Diabetes mellitus is a risk factor for adverse
• Individualise when to stop pregnancy outcomes such as birth defects,
renin-angiotensin-aldosterone pre-eclampsia, growth restriction, foetal
system (RAAS) blockade macrosomia, stillbirth (risk correlated with
pre-pregnancy or at time of glycemic control)
positive pregnancy test with • Proteinuria increases the risk for venous
appropriate switch in thromboembolism
medications if required
Lupus nephritis • Anti Ro and La antibodies (if • Pregnancy can trigger a relapse
(LN) present) can cross the placenta • Increased risk for adverse pregnancy outcomes
and confer a 2% risk of • Proteinuria (if present) increases the risk for
congenital heart block (CHB) venous thromboembolism
and 5% risk of neonatal
cutaneous lupus
24 An Approach to Obstetric Nephrology 491
along with targets to be achieved and specifics patients and this should be addressed and opti-
pertaining to each condition. mised prior to pregnancy. The importance of
optimisation of blood pressure control prior to
conception should also be reiterated.
Preparation for Pregnancy For genetic kidney conditions such as adult
polycystic kidney disease (APKD) or Alport
Pre-pregnancy counselling is essential, and each syndrome, women should be counselled on the
consultation with a woman with CKD is an excel- risk of inheritance for their offspring. Timely
lent opportunity to optimise and prepare for a genetic work-up if not previously performed and
future pregnancy. Lifestyle modifications include genetic counselling is key. Consideration for
smoking cessation, weight management and reg- preimplantation genetic testing (PGT) for some
ular exercise. The importance of achieving dis- genetic conditions may be possible, although
ease stability and conversion of potentially access to PGT may be limited depending on
teratogenic medications to pregnancy favourable location, and the indications for PGT and poli-
medications should be discussed at the precon- cies policing it also vary widely in different parts
ception visit in conjunction with the relevant spe- of the world.
cialists, with clinical decisions individualised Table 24.2 summarises the common drugs
based on the factors such as the underlying kid- used in pregnancy for women with CKD.
ney condition, degree of kidney impairment or
proteinuria and the likelihood of continued quies- Clinical Scenario 1
cent disease with change in medications. A 32 year old woman with Type I diabetic for the
Important preconception supplements include past 16 years presents to the preconception clinic.
at least 400 μg of folic acid, or high dose 5 mg She is planning her 4th pregnancy. Her creatinine
folic acid for women with diabetes, as well as is 122 μmol/L and her urine protein:creatinine
vitamin D supplementation. Folic acid should ratio (uPCR) is 142 mg/mmol. Her HbA1c is
ideally be initiated 3 months prior to conception. 88mmol/mol. She is on basal bolus insulin:
Anaemia is a common complication in CKD Novorapid and Levemir.
Table 24.2 Safety profile of medications for kidney disease during pregnancy and breastfeeding
Medication Pregnancy Breastfeeding
Azathioprine Safe Compatible
Steroids Safe but increased risks of gestational diabetes, hypertensive Compatible
disorders of pregnancy, infection, preterm delivery
MMF Teratogenic. Avoid
Avoid in pregnancy and stop at least 6 weeks before a
planned pregnancy.
Calcineurin inhibitors (CNI) e.g. Safe but increased risks of gestational diabetes and Compatible
tacrolimus, cyclosporin hypertensive disorders of pregnancy
Cyclophosphamide Teratogenic, Limited data
Avoid in pregnancy.
Can be considered for use in the 2nd and 3rd trimester if
required as no adverse effects have been observed in
observational studies.
Rituximab Stop 6 months prior to conception. Limited data
Although limited evidence has not shown it to be teratogenic,
2nd and 3rd trimester exposure is associated with neonatal B
cell depletion.
Biologics e.g. eculizumab Safe Compatible
Hydroxychloroquine Safe Compatible
• What pre-pregnancy counselling would you done to assess for foetal defects. Pregnancies
offer her? complicated by CKD should also have serial
–– Advise her regarding the increased risk of growth scans in the third trimester for monitoring
deterioration of her kidney disease with of foetal well-being.
any future pregnancies and the implica- With regard to maternal surveillance for
tions of this pregnancies complicated by CKD, monthly kid-
–– Counsel her on the importance of achiev- ney function tests and urine protein:creatinine
ing optimal blood glucose and blood pres- ratio (uPCR) measurement is recommended.
sure control prior to conception Increasing the frequency of monitoring in the
–– Advise her to continue effective contracep- third trimester can be considered, especially if
tion until her glycaemic control has there is a suspicion of superimposed PET or
improved as the risk of congenital anomaly progression of kidney disease, so that decisions
increases with increasing HbA1c level. regarding timing of delivery can be made whilst
–– Advise her to remain on Ramipril 2.5 mg balancing maternal and foetal health. It is also
until she has a positive pregnancy test important to continue treatment of maternal
–– Commence 5 mg folic acid three months anaemia and optimising the haemoglobin
prior to conception to reduce the risk of throughout pregnancy, and especially around
congenital anomaly the time of delivery for maternal and foetal
benefits.
Antenatal Care
Management of Hypertension
An early review by the multidisciplinary team in the Preconception, Antenatal
(MDT) comprising nephrologists, maternal foe- and Postnatal Period
tal medicine specialists, obstetric physicians and
midwives is important for timely individualisa- The recommended first-line choice of anti-
tion of care and surveillance. hypertensives drugs in pregnancy include labet-
Women with CKD are at higher risk of devel- alol and nifedipine. Methyldopa, which had
oping pre-eclampsia (PET). There is strong evi- traditionally been used widely in pregnancy in the
dence that low dose aspirin 75–150 mg taken past, is less commonly used now because of its
from 12 to 36 weeks of pregnancy reduces the association with antenatal and postnatal depres-
risk of PET. A recent randomised clinical trial sion. Angiotensin-converting enzyme inhibitors
found a 62% reduction in preterm PET in women (ACE-I) and angiotensin II receptor blockers
taking aspirin 150 mg nocte from 11–14 weeks to (ARBs) used in renin-angiotension- aldosterone
36 weeks of gestation as compared with placebo system (RAAS) blockade are contraindicated in
[3]. In addition, women with significant baseline pregnancy, except in the rare event of a sclero-
proteinuria of >100–150 mg/mmol should be risk derma renal crisis (Table 24.3). For women with
stratified for venous thromboembolism, with diabetic nephropathy, the timing of discontinua-
consideration to initiating low molecular weight tion of RAAS blockade, e.g. either during the pre-
heparin (LMWH) prophylaxis during pregnancy conception period or at time of a positive urine
and up to 6 weeks postpartum. pregnancy test, should be individualised based on
With regard to foetal surveillance for pregnan- the severity of proteinuria or kidney function
cies complicated by CKD, women with CKD impairment. In making these decisions, it is
exposed to teratogenic drugs in the first trimester important also to understand that women with
should be referred to a specialist foetal medicine CKD may experience reduced fecundity and may
unit, with appropriate detailed anomaly scan require a longer time to conceive.
Table 24.3 Common anti-hypertensive medications used during pregnancy and breastfeeding
Anti-hypertensive
medication used in
hypertensive
Class of drug Risk of Teratogenicity Breast Feeding emergencies
Calcium channel blockers None Limited data Nifedipine MR oral
e.g. nifedipine MR, No adverse effects (Risk of headaches)
amlodipine reported with
amlodipine
Β-blockers None Limited data-widely Labetalol infusion
e.g. bisoprolol used (Risk of nausea and
α/β blockers Compatible dizziness)
e.g. labetalol
Central α-adrenergic None Compatible
e.g. Methyldopa
α-adrenergic blockers None Not recommended for
e.g. doxazosin, prazosin routine use in
pregnancy unless no
alternatives available
Peripheral arterial None Compatible Hydralazine infusion
vasodilator (Risk of maternal
e.g. hydralazine tachycardia &
hypotension)
ACE-inhibitors Yes Compatible
e.g. enalapril, captopril Lowest incidence of birth defects
with exposure in the 1st trimester
Risk of foetal anomalies in the
2nd and 3rd trimester e.g. foetal
kidney damage
With regard to blood pressure targets used in 88mmol/mol. She is on basal bolus insulin:
pregnancy, the Control of Hypertension in Novorapid and Levemir.
Pregnancy Study (CHIPS) trial published in 2015
demonstrated that targeting a tighter diastolic blood • What would be the treatment target for her
pressure of <85 mmHg had benefits of a reduced blood pressure in pregnancy?
likelihood of developing accelerated maternal –– There is increasing expert consensus that
hypertension, without increasing the risks of hypertension in pregnant women with CKD
adverse foetal outcomes as compared to less tight should be treated, with a target average
(100 mmHg) control [4]. Although the CHIPS trial blood pressure of <130/80 mmHg [5]. In
did not include women with proteinuria, there is addition, the results of the CHIPS trial
increasing expert consensus that hypertension in found that targeting a tighter diastolic blood
pregnant women with CKD should be treated to a pressure of <85 mmHg was associated with
target blood pressure of <130/80 mmHg [5]. a reduced likelihood of developing acceler-
ated maternal hypertension and its risks,
Clinical Scenario 1 without increasing the risks of adverse foe-
A 32 year old woman with Type I diabetic for the tal outcomes as compared to less tight
past 16 years presents to the preconception clinic. (100 mmHg) control [4]. The results of the
She is planning her 4th pregnancy. Her creatinine CHIPS trial may not be entirely reproduc-
is 122 μmol/L and her urine protein:creatinine ible in women with CKD as this study did
ratio (uPCR) is 142 mg/mmol. Her HbA1c is not include women with proteinuria.
Diagnosing Pre-Eclampsia As for women with chronic hypertension and

in the Context of Pre-Existing proteinuria, the guideline recommends that the
Kidney Disease development of sustained severe hypertension
(systolic BP >160 mmHg and/or diastolic BP
The traditional definition of pre-eclampsia is that >110 mmHg or doubling of antihypertensive
of new onset of hypertension and proteinuria agents) and/or a substantial rise in proteinuria
after the 20th gestational week. It can therefore (doubling of uPCR or uACR compared to early
be very challenging to make a diagnosis of pre- pregnancy) should prompt clinical assessment
eclampsia in women with pre-existing hyperten- for superimposed pre-eclampsia.
sion, kidney impairment, proteinuria—a The guidelines also make mention of the role
combination that is frequently seen in women of angiogenic markers, namely placental growth
with CKD. An important point to note is that factor (PlGF) and soluble fms-like tyrosine
newer definitions of pre-eclampsia, such as that kinase-1 (sFlt-1), as adjuncts to diagnose super-
from the International Society of the Study of imposed pre-eclampsia. This is further elaborated
Hypertension in Pregnancy (ISSHP) recognise in the section on pre-eclampsia later in this
that even in the absence of proteinuria, if there is chapter.
new onset hypertension associated with either
systemic effects in the form of biochemical Clinical Scenario 1
derangements (e.g. deranged liver function tests, A 32 year old woman with Type I diabetic for the
raised serum creatinine levels) or evidence of pla- past 16 years presents to the preconception clinic.
cental insufficiency (e.g. foetal growth restric- She is planning her 4th pregnancy. Her creatinine
tion), a diagnosis of pre-eclampsia can be made. is 122 μmol/L and her urine protein:creatinine
This is further illustrated in the later part of the ratio (uPCR) is 142 mg/mmol. Her HbA1c is
chapter, discussing pre-eclampsia. Other bio- 88mmol/mol. She is on basal bolus insulin:
chemical markers and foetal growth should there- Novorapid and Levemir.
fore come into the picture when establishing a
diagnosis of pre-eclampsia in women with CKD. • How would you recognize the development of
A clinical practice guideline on pregnancy and superimposed pre-eclampsia?
kidney disease published by The UK Kidney –– Regular blood pressure monitoring with
Association has made recommendations to help attention to the development of any new
with the above clinical conundrum [6]. This onset hypertension (systolic blood pres-
guideline recommends that a diagnosis of super- sure >130 mmHg and/or diastolic BP
imposed pre-eclampsia be considered: >80 mmHg), monitoring for maternal
organ dysfunction in the form of biochemi-
• In a woman with non-proteinuric CKD, if she cal parameters and symptoms, and sur-
develops new hypertension (systolic BP veillance of foetal growth are crucial steps
>140 mmHg and/or diastolic BP >90 mmHg) to making a diagnosis of superimposed
and proteinuria (uPCR >30 mg/mmol or pre-eclampsia. In this particular case,
uACR >8 mg/mmol) or maternal organ dys- where the mother has significant pre-exist-
function after 20 weeks’ gestation. ing proteinuria, a diagnosis of superim-
• In a woman with proteinuric CKD if she posed pre-eclampsia should be considered
develops new hypertension (systolic BP if she develops new onset hypertension or
>140 mmHg and/or diastolic BP >90 mmHg) any evidence of maternal organ dysfunc-
or maternal organ dysfunction after 20 weeks’ tion or uteroplacental dysfunction after
gestation. 20 weeks’ gestation. The diagnosis of
• In a woman with chronic hypertension and superimposed pre-eclampsia should also
proteinuria, if she develops maternal organ be considered if there is a substantial rise
dysfunction after 20 weeks’ gestation. in proteinuria e.g. doubling of uPCR com-
pared to early pregnancy values. Adjuncts pregnancy in kidney transplant recipients

such as the use of placental growth factor remains challenging, although the risks with
(PlGF) can also be useful in ruling out pregnancy are greater in women with very
superimposed pre-eclampsia in the correct advanced CKD compared with women with a
clinical context. kidney transplant. In helping to decide on suit-
ability for conception, a detailed review of
allograft function, stability of serum creatinine
Dialysis and Pregnancy post-transplant and immunosuppressant medi-
cations is required. Stability for at least one year
The indications for kidney replacement therapy prior to conception after a transplant is advised.
(KRT) in pregnancy are similar to those in the The risk of deterioration in kidney function
non-pregnant population and include metabolic should be discussed in the preconception period,
acidosis, hyperkalemia, and fluid overload and women on teratogenic medications such as
refractory to medical treatment. However, in mycophenolate mofetil (MMF) should be
addition to that in the context of pregnancy switched to alternative medications that are
would be raised urea levels (> 17mmol/L) more compatible with pregnancy. The recom-
despite medical management as significant urea mended maintenance immunosuppression drugs
levels can lead to foetal diuresis and polyhy- for pregnant women are calcineurin inhibitors
dramnios and foeto-toxicity. (CNIs) (e.g. tacrolimus, cyclosporine), azathio-
Pregnancy rates in women on peritoneal dialysis prine, and prednisolone. Risk factors associated
(PD) are lower than on those on haemodialysis. with an increased risk of adverse pregnancy out-
Studies have shown increased dialysis fre- comes include pre-existing hypertension, a
quency e.g. daily haemodialysis are associated serum creatinine level of more than 124 μmol/L,
with lower rates of preterm delivery and low history of more than 2 kidney transplants, as
birthweight babies. There is a paucity of data for well as proteinuria.
the precise duration of dialysis needed to opti- Women with a kidney transplant should
mize outcomes. Women who initiate dialysis book for their antenatal care at the earliest pos-
during pregnancy have improved outcomes com- sible opportunity, once pregnancy is confirmed.
pared with those who conceive on dialysis. In Close attention to kidney function and moni-
general, the current expert consensus is that dial- toring of immunosuppressant trough levels of
ysis should be initiated when maternal urea tacrolimus or cyclosporine throughout preg-
reaches levels of 17–20 mmol/L [6]. nancy is important: women may require higher
Erythropoietin stimulating agents (ESAs) are doses of cyclosporine and tacrolimus during
safe for use in pregnancy, and can be an impor- pregnancy. Post-delivery, the levels of tacroli-
tant adjunct in maintaining optimal haemoglo- mus and cyclosporine should continue to be
bin levels, which is important for mother and monitored, as dose reductions will likely be
foetus. required if the dose had been increased in preg-
nancy. Regular review of blood pressure and
proteinuria is advised so that deterioration in
Kidney Transplantation kidney function or superimposed PET can be
and Pregnancy identified.
In addition, women on steroids or calcineurin
More women are now successfully achieving inhibitors have a higher risk of developing gesta-
conception after kidney transplantation, particu- tional diabetes mellitus (GDM). It is important to
larly over the past two decades, due to advances screen for GDM with an oral glucose tolerance
in treatments and surgery, as well as better test and optimise the blood sugar profile if GDM
access to transplant centres. The management of is diagnosed.
Contraception in Women with CKD diagnostic threshold for kidney injury in preg-
nancy [7]. AKI is associated with increased
All healthcare professionals should have a clear morbidity and mortality for both the mother and
understanding of options for contraception in foetus regardless of the underlying cause which
women with CKD. Decision-making on appro- can be either pregnancy specific (e.g. pre-
priate contraception needs to be individualised eclampsia, acute fatty liver of pregnancy) or
based on risks, acceptability to the patient and non-pregnancy specific (e.g. sepsis, hypovole-
likelihood of compliance. In general, oestrogen- mia). The causes of AKI in pregnancy can be
containing contraceptive methods (e.g. com- divided into three groups as listed in Table 24.4:
bined oral contraceptive pills, contraceptive pre-renal, renal and post-renal or obstructive
patch) should be avoided because of its asso- causes. These aetiologies may be overlapping
ciation with increased blood pressure, as well and therefore AKI in pregnancy is a heteroge-
as increased risks for thrombotic or vascular neous syndrome, defined as occurring during
events. Progestogen-only contraception [e.g. pregnancy, labour and the postpartum period
progestogen- only pill, intramuscular Depo- There are usually multiple co-existing factors
Provera® contraceptive injection, intrauter- for the development of AKI in pregnancy, with
ine system (Mirena®), implant (Nexplanon®)] pregnancy-specific complications such as PET,
are favoured for women with CKD as they are postpartum haemorrhage and sepsis. High vigi-
safe and effective. Barrier methods are accept- lance is required.
able options as well, although its effectiveness
and reliability with typical use is much lower Clinical Scenario 2
compared to other forms of contraception. A 29 year old primiparous woman presents at 24
Sterilisation (female and male) is effective but weeks’ gestation feeling unwell with a blood
irreversible, and can be considered if the couple pressure of 180/95 mmHg. Her serum creatinine
has completed their family or is certain that level is 222 μmol/L, and her platelet count is
future conception is not desired. 22 × 109/L.
cute Kidney Injury (AKI)

A Table 24.4 Causes of acute kidney injury in pregnancy
and the postpartum period
in Pregnancy
Pre- • Sepsis e.g. pyelonephritis,
renal chorioamnionitis, septic abortion
Clinical Scenario 2 • Dehydration e.g. hyperemesis
A 29 year old primiparous woman presents at gravidarum
24 weeks’ gestation feeling unwell with a blood • Hypovolemia e.g. antepartum or
pressure of 180/95 mmHg. Her serum creatinine postpartum haemorrhage
Renal • Drug-related causes e.g. non-steroidal
level is 222 μmol/L, and her platelet count is
anti-inflammatory drug (NSAID)-
22 × 109/L. induced AKI
• Pre-eclampsia
• What are your differential diagnoses? • Haemolysis, elevated liver enzymes,
low platelets (HELLP) syndrome
• What focused investigations would you con-
• Acute Fatty Liver of Pregnancy (AFLP)
sider performing? • Atypical Haemolytic Uraemic
• How would you manage her? Syndrome (aHUS)
• Thrombotic Thrombocytopenic Purpura
(TTP)
The current international consensus definitions
• New onset glomerulonephritis
for acute kidney injury (AKI) in the general Post- • Obstruction
population have not been validated for preg- renal • Ureteric injury (intra-operatively during
nancy. It has been suggested that a new creati- caesarean delivery)
nine level of > 77umol/L should be the • Neuropathic bladder with retention
• What are your differential diagnoses? Investigations for AKI in pregnancy should be
–– Pre-eclampsia performed in a timely and focused manner.
–– Haemolysis, elevated liver enzymes, low Table 24.5 discusses the common investigations
platelets (HELLP) syndrome performed as part of the diagnostic workup for
–– Atypical Haemolytic Uraemic Syndrome AKI in pregnancy.
(aHUS)
–– Thrombotic Thrombocytopenic Purpura Clinical Scenario 2
(TTP) A 29 year old primiparous woman presents at
–– New onset glomerulonephritis 24 weeks’ gestation feeling unwell with a blood
Table 24.5 Investigations for AKI in pregnancy

Type of
test Specific test Rationale for test Pregnancy specific changes
Blood Full blood count • To look for anaemia that may be a • Expansion in plasma volume
(FBC) result of chronic kidney disease or leads to a fall in haemoglobin
acute causes such as blood loss or levels. (Hb of 100–110 g/L
haemolysis considered normal for
pregnancy)
• Platelet count tends to fall
progressively during normal
pregnancy, hence significant
thrombocytopenia
is considered if the platelet
count is less than 100 × 109/L
Urea, creatinine, • To assess the degree of severity of • Serum creatinine levels
electrolytes the kidney function and determine decrease in pregnancy. If this is
the need for dialysis not observed, it could
• To assess for electrolyte potentially be a red flag as there
abnormalities associated with AKI is an absence of normal renal
and correct as necessary physiological adaptation
Liver function test • Presence of transaminitis may • Pregnancy ranges for
(LFT) point towards HELLP syndrome transaminases ALT and AST
or acute fatty liver of pregnancy are largely similar to non-
(AFLP) pregnant individuals
Lactate • To assess for the presence of • Reference ranges does not
dehydrogenase haemolysis change in pregnancy
(LDH)
Peripheral blood film • To assess for signs of • No pregnancy related changes
microangiopathic haemolytic in pregnancy
anaemia (MAHA)
Clotting studies • Can be deranged in severe • Levels of factors VIII, IX and X
pre-eclampsia, HELLP syndrome, are increased
acute fatty liver of pregnancy • Fibrinogen levels are increased
(AFLP) and disseminated • Antithrombin, protein S &
intravascular coagulation (DIC) protein C levels decrease
ADAMTS-13* • Significantly low levels of • This is slightly reduced in
activity ADAMTS-13 activity (<10%) can pregnancy
be diagnostic for thrombotic
thrombocytopenic purpura (TTP)
Urine Protein measurement • To assess for the presence of • uPCR >50 mg/mmol can be
(urine proteinuria which can be suggestive of PET if there had
protein:creatinine associated with pre-eclampsia been no proteinuria prior to
ratio (uPCR)) especially if new onset conception
• If detected, quantifying the
proteinuria may be useful in
guiding decisions regarding
thromboprophylaxis
(continued)

Type of
test Specific test Rationale for test Pregnancy specific changes
Urine microscopy and • To look for urinary tract sepsis • Urinary stasis in the dilated
culture collecting system
• predisposes pregnant women
with asymptomatic bacteriuria
and can lead to pyelonephritis.
• All asymptomatic bacteriuria
should be treated
Urine phase contrast • The presence of abnormal urinary • Reference ranges does not
microscopy sediment such as red blood cell change in pregnancy
casts may indicate an underlying
kidney pathology
Imaging Ultrasound kidneys • Exclude obstruction as a cause for • Increased renal blood flow
MRI AKI leads to an increase in renal
CT KUB • Bilateral small kidneys may be size of 1–1.5 cm
indicative of underlying CKD • Commonly, right-sided
• MRI (non-contrast) and CT pelvicalyceal prominence due
imaging modalities are safe in to the anatomical circumstances
pregnancy and during lactation. of the right ureter crossing the
CT contrast may exacerbate iliac and ovarian vessels at an
existing AKI, hence the benefits angle before entering the pelvis
versus risks of performing the test
should be individualised
Histology Kidney biopsy • Rarely required for diagnostic
workup of AKI in pregnancy
• Reserved for severe pregnancy-
related AKI or nephrotic syndrome
warranting a definitive diagnosis
with established therapy or when
prolongation of pregnancy is a
priority e.g. in the 1st or 2nd
trimester
• Risks of kidney biopsy in the form
of bleeding risk are higher in
pregnancy (7%) compared to
outside of pregnancy (1%) [8].
pressure of 180/95 mmHg. Her serum creatinine pecific Conditions and Their
S
level is 222 μmol/L, and her platelet count is Management
22 × 109/L.
Pre-eclampsia
• What focused investigations would you con-
sider performing? Pre-eclampsia is a multisystem disorder that
Urgent complicates 3–8% of pregnancies and constitutes
–– Full blood count, renal profile, liver profile, a major source of morbidity and mortality world-
clotting profile wide. In Latin America and the West Indies,
–– Urine protein:creatinine ratio (uPCR) hypertensive disorders contribute to almost 26%
–– Peripheral blood film of maternal deaths. In Africa and Asia they con-
–– ADAMTS-13* activity tribute to 9% of all maternal deaths. Traditionally,
pre-eclampsia is defined as new-onset hyperten- Table 24.6 The revised ISSHP Definition of Pre-
eclampsia [9]
sion developing after 20 weeks of gestation in the
presence of proteinuria. Newer definitions in Hypertension developing after 20 weeks’ gestation
and the coexistence of one or more of the following
recent years have recognised that even in the new onset conditions:
absence of proteinuria, new-onset hypertension 1. Proteinuria
associated with other maternal organ dysfunction 2. Other maternal organ dysfunction
or uteroplacental dysfunction would similarly (a) Kidney insufficiency (creatinine > 90 μmol/L)
qualify as a diagnosis of pre-eclampsia. The (b) Liver involvement (elevated transaminases and/
or severe right upper quadrant or epigastric pain)
revised International Society for the Study of (c) Neurological complications (e.g. eclampsia,
Hypertension in Pregnancy (ISSHP) definition of altered mental state, blindness, stroke or more
pre-eclampsia is reflected in Table 24.6 [9]. commonly hyperreflexia when accompanied by
Placental growth factor (PLGF) based testing clonus, severe headaches when accompanied by
hyperreflexia, persistent visual scotoma
can be used as a diagnostic adjunct and a confir- (d) Haematological complications
matory test in women with suspected PET. The (thrombocytopenia, disseminated intravascular
PELICAN Study demonstrated that the negative coagulopathy (DIC), haemolysis)
predictive value of PlGF using a cut-off value of 3. Uteroplacental dysfunction
(a) Foetal growth restriction
more than 100 picograms/mL in women present-
ing with suspected pre-eclampsia between
20 weeks and 34 weeks plus 6 days of gestation hydralazine, common side effects include
was 98% [10]. maternal tachycardia and hypotension which
Pre-eclampsia leads to AKI in around 1.5–2% can be reduced by adequate hydration prior to
of cases [11]. The presence or absence of AKI in administration.
pre-eclampsia can be used as a marker of severity (b) Prevention of convulsions (eclampsia)
which may affect obstetric decisions such as tim- Magnesium sulphate is recommended for
ing of delivery. the prevention of eclampsia in women with
The principles of management of pre-eclampsia severe pre-eclampsia and is the drug of
are: choice for neuroprotection for the foetus
before 32 weeks of gestation. This is admin-
(a) Control of blood pressure istered as a loading dose of 4 g IV over
(b) Prevention of convulsions (eclampsia) 5–15 mins followed by a maintenance dose
(c) Fluid management of 1 g/h by continuous infusion for 24 h or
(d) Timely delivery until 24 h after delivery or last convulsion,
whichever is later. In cases with underlying
kidney impairment, administering the same
(a) Control of blood pressure bolus dose of magnesium sulphate and then
A blood pressure reading of 160/110 mmHg halving the maintenance dose to 0.5 g/h with
is an obstetric emergency. The goal of treat- regular surveillance of serum magnesium
ment is to aim for a systolic blood pressure levels would be the recommended approach.
of <140 mmHg to reduce the risk of intrace- Further dose adjustments may be required to
rebral haemorrhage. Commonly used anti- avoid maternal toxicity, and in cases of
hypertensive agents for the control of blood anuria, may require cessation entirely.
pressure at this time include oral nifedipine (c) Fluid management
MR and intravenous labetalol and hydrala- Endothelial damage as a result of pre-
zine. Common side-effects with intravenous eclampsia can also lead to pathologic c apillary
labetalol include nausea and dizziness. With leak that can present in the mother as oedema,
rapid weight gain, haemoconcentration and HELLP Syndrome

pulmonary oedema. Oliguria may be observed
in pre-eclampsia because of intrinsic kidney HELLP syndrome is a complication of pregnancy
disease (including acute tubular necrosis), and characterised by haemolysis, elevated liver
may not respond to plasma volume expansion. enzymes and low platelets, and is typically asso-
Excessive intravenous hydration in women ciated with severe pre-eclampsia. It occurs in
with pre- eclampsia can potentially lead to 0.5–0.9% of all pregnancies and 10–20% of
complications such as pulmonary oedema. It severe pre-eclampsia, and may not always pres-
is recommended for women with pre- ent as full blown HELLP syndrome with all fea-
eclampsia to avoid aggressive fluid resuscita- tures, but can present as an incomplete HELLP
tion, with fluid restriction of 85–100 mL/h syndrome with only some of the features. The
recommended in the peripartum period. majority of patients with HELLP syndrome will
Regular review and judicious assessment and present with hypertension and proteinuria, but
management of fluid status is paramount. the condition may also occur without these symp-
(d) Timely Delivery toms and manifest only later on.
Delivery leads to eventual resolution of The incidence of kidney impairment is higher
the disease progression for pre-eclampsia. in HELLP syndrome than in pre-eclampsia, with
Decisions regarding timing of delivery in AKI complicating 3–15% of cases. The risk of
pre-eclampsia requires consideration of the AKI increases if complications associated with
potential neonatal risks of prematurity versus HELLP occur, such as abruption, disseminated
maternal risks for severe morbidity or mor- intravascular coagulation (DIC), haemorrhage,
tality in continuing the pregnancy. Shared intrauterine death or sepsis, and AKI in the con-
decision-making using a multidisciplinary text of HELLP syndrome worsens prognosis.
approach is required. Laboratory abnormalities of HELLP syn-
Women with pre-eclampsia should be fol- drome typically worsen after delivery and peak
lowed up closely in the postpartum period, at 24-48 hours postpartum. Haematological and
and assessment for resolution of proteinuria biochemical abnormalities should be expected
and normalization of blood pressure should be to gradually return to pre-pregnancy values
performed. Complete resolution of the effects thereafter. If these laboratory abnormalities do
of pre-eclampsia can take up to 12 weeks post- not recover after delivery, and if AKI and throm-
delivery. In cases of persistent proteinuria, bocytopenia dominate the clinical picture, then
consideration for referral to a Nephrologist consideration for alternative diagnoses of
for further diagnostic workup should be made. thrombotic microangiopathies such as throm-
It is important to know that even in individu- botic thrombocytopenic purpura (TTP) and
als who have completely recovered from pre- atypical haemolytic uremic syndrome (aHUS)
eclampsia, they go on to have a higher risk for should be considered.
hypertensive and cardiovascular disorders, not The management of HELLP syndrome is
just in future pregnancies, but also in later life largely supportive, and mirrors that of pre-
outside of pregnancy. In addition, pre-eclamp- eclampsia. Delivery is the definitive management
sia, particularly early pre-term pre-eclampsia, for this condition. In general, if the pregnancy is
has been found to be strongly associated with less than 34 weeks’ gestation, provided that
several chronic kidney disorders later in life maternal and foetal condition remains stable,
[12]. Women with pregnancies complicated by delivery can be performed after completion of
pre-eclampsia should be counselled on the risk steroids for foetal pulmonary maturation. For
of recurrence of hypertensive disorders of preg- pregnancies beyond 34 weeks of gestation,
nancy in future pregnancies, and advised about women with HELLP syndrome should generally
lifelong regular blood pressure surveillance. be delivered soon after maternal stabilisation.
Thrombotic Microangiopathies The risk of recurrence of TTP in future preg-

(TMAs) nancies is 92% for women with congenital TTP,
47% for women with acquired idiopathic TTP, and
Thrombotic thrombocytopenic purpura (TTP) and 45% for acquired pregnancy-associated TTP [14].
atypical haemolytic uremic syndrome (aHUS) are Women with a previous history of TTP should
thrombotic microangiopathies that may both mas- undergo appropriate pre-pregnancy counselling by
querade as and co-exist with pre- eclampsia in a multidisciplinary team. They should be moni-
pregnancy. Although these three conditions have tored closely for development of TTP in their next
similar clinical features, they are in actual fact very pregnancies. With regard to the management of
distinct entities. with distinct etiologies, pathogen- women who had previous pregnancies compli-
esis and treatment, which lends point to the impor- cated by TTP, regular 2-weekly plasma exchange,
tance of being able to distinguish between them. starting from the 1st trimester of pregnancy, with a
Although TTP and aHUS are not commonly seen view to increasing the frequency from the late 2nd
conditions, each with an incidence of only 1 in trimester to 3rd trimester as guided by FBC and
25,000 pregnancies, both can potentially lead to LDH levels, can be a suitable approach.
significant maternal and foetal morbidity, and even
mortality. It is therefore important to have a high typical Haemolytic Uraemic
A
index of suspicion for these conditions in the cor- Syndrome (aHUS)
rect clinical context, so that early recognition and Atypical HUS is a type of TMA characterized by
treatment can be achieved. intravascular haemolysis, thrombocytopenia, and
acute kidney failure, with the underlying
Thrombotic Thrombocytopaenic pathophysiology being that of uncontrolled com-
Purpura (TTP) plement activation. Although the majority (80%)
TTP is typically characterised by the pentad of of women with aHUS are diagnosed in the post-
fever, microangiopathic anaemia, thrombocyto- partum period, with potential triggers being
penia, kidney failure and neurologic findings. infection or postpartum haemorrhage, it can pres-
However, not all individuals with TTP will have ent in any gestation of pregnancy as well, even as
the full pentad—only 40% may present with all 5 early as the 1st trimester. The treatment of aHUS
clinical manifestations. The median age of pre- is largely supportive, comprising of red cell
sentation with acute TTP is in the 3rd to 4th transfusion, blood pressure control, and dialysis
decade of life, typically affecting women. TTP in (if required). Specific treatment for aHUS
pregnancy can be acquired (90%) or may mani- includes the use of eculizumab, a humanized IgG
fest as an initial, delayed presentation of congeni- monoclonal therapy that is a potent inhibitor of
tal TTP disease (10%). Severe ADAMTS-13 C5 cleavage, and aids in overall complement
deficiency is defined as less than 10% of normal inhibition. Safety data for use of eculizumab in
activity, with this having an approximately 90% pregnancy is extrapolated from its use in treat-
sensitivity and specificity for the diagnosis of ment of paroxysmal nocturnal haemoglobinuria
TTP. Pregnancy can trigger the onset of TTP, as (PNH) in pregnancy, where foetal mortality and
von Willebrand factor increases with gestation, miscarriage rates have been demonstrated to
whilst ADAMTS-13 activity reduces in the 2nd being comparable or better than untreated preg-
and 3rd trimester of pregnancy. The mainstay of nant women with PNH [15].
treatment for TTP is plasma exchange, which
may allow for prolongation of pregnancy if time
required for foetal maturation is desired. Postpartum Haemorrhage (PPH)
Recognition of the diagnosis, together with active
monitoring and management during pregnancy Postpartum PPH can be divided into primary and
results in positive pregnancy outcomes [13]. secondary PPH, with the former referring to PPH
Table 24.7 Definition of Postpartum Haemorrhage Table 24.8 Table of maternal weight when estimating
(PPH) blood loss and its consequences
Primary Bleeding per vagina > 500mL within 15% 30% 40%
PPH 24 h of delivery Estimated blood blood blood
Secondary Bleeding per vagina >500 mL more than Maternal total blood loss loss loss
PPH 24 weight volume (mL) (mL) (mL)
hours but less than 6 weeks after delivery 50 kg 5000 750 1500 2000
Minor Loss of 500–1000 mL of blood from the 60 kg 6000 900 1800 2400
PPH genital tract after the birth of a baby 70 kg 7000 1050 2100 2800
Major Loss of >1000 mL of blood from the 80 kg 8000 1200 2400 3200
PPH genital tract after the birth of a baby
Massive Postpartum blood loss >2000 mL or
PPH lesser amounts resulting in changes in lemic shock. The aim of management is to pre-
haemodynamic parameters which lead to vent progression of mild PPH to major or massive
moderate or severe hypovolemic shock haemorrhage, that carries a worse prognosis and
increased risk of AKI or permanent kidney
occurring within the first 24 h of delivery, and the damage.
latter referring to PPH at any time point after the In low resource settings, approaches to mini-
first 24 h up to 6 weeks after delivery. Table 24.7 mise blood loss and mitigate the effects of mas-
lists the various definition and severity classifica- sive haemorrhage include bimanual uterine
tion of PPH. It is important to remember that compression, aortic compression, and applying
individuals with pre-existing anaemia (e.g. those clamps to arrest bleeding from cervical and vagi-
with anaemia secondary to CKD) have a lower nal tears before referral or whilst waiting to be
tolerance to blood loss in general. transferred to the operating theatre. These should
The common causes of postpartum haemor- be done concurrently along with measures to
rhage can be divided into the 4Ts: maintain circulation.
• Tone—uterine atony is the most common Clinical Scenario 2

cause of PPH A 29 year old primiparous woman presents at
• Trauma—tears in vagina, cervix, vulva 24 weeks’ gestation feeling unwell with a blood
• Tissue—retained placental tissue pressure of 180/95 mmHg. Her serum creatinine
• Thrombin—DIC/HELLP/coagulation level is 222 μmol/L, and her platelet count is
disorders 22 × 109/L.
Healthcare providers have a tendency to underes- • How would you manage her?
timate blood loss and efforts at visual quantifica- –– Admit to a high dependency unit
tion does help standardize the amount of blood –– Intravenous access
loss, especially in low resource settings [16]. It is –– Treat blood pressure appropriately
also important to recognise how differences in –– Assess for microangiopathic thrombotic
maternal weight with its corresponding estimated causes such as HELLP syndrome, atypical
total blood volume can contribute to varying haemolytic uremic syndrome (aHUS) or
severity and impact on the individual. Table 24.8 thrombotic thrombocytopenia purpura
demonstrates this. (TTP) by performing appropriate
Management of PPH requires early diagnosis, investigations
a team approach to simultaneously minimise or –– Treat based on likely diagnosis. If HELLP
arrest the bleeding and maintain circulating blood syndrome is diagnosed, delivery after sta-
volume through replacing blood products if blood bilisation is recommended. If TTP is con-
loss more than 1000 mL and ongoing or any firmed, treatment with plasma exchange
patient triggers that indicate impending hypovo- should be initiated.
Conclusions D. Pre-eclampsia
E. Progression of chronic kidney disease-
Case 1 highlights the importance of pre- Answer: A
pregnancy counselling and surveillance of 4. The perinatal risk for chronic kidney dis-
chronic kidney disease during pregnancy. Case 2 ease in pregnancy include the following,
highlights the importance of timely investiga- except:
tions and recognition of AKI in pregnancy. The A. Fetal growth restriction
worldwide burden of CKD and AKI in preg- B. Hypercalcaemia
nancy and the inequalities in access to point of C. Lower birth weight
care testing and novel treatment options make a D. Perinatal mortality
compelling demand to develop more global col- E. Stillbirth
laboration and understanding of kidney disease Answer: B
in pregnancy. 5. Investigations at booking for a patient with
diabetic nephropathy in pregnancy include
the following:
Questions A. Brain natriuretic peptide (BNP)
B. Bone profile
C. Erythrocyte sedimentation rate (ESR)
1. In the management of a patient with Chronic D. Renal profile
Kidney Disease in pregnancy, the following E. Renin-aldosterone ratio
are true except: Answer: D
A. Maintaining the Diastolic Blood Pressure 6. Surveillance for ongoing antenatal review of
less than 85 mmHg improves pregnancy include the following EXCEPT:
B. A serum creatinine of 100 μmol/L is con- A. Blood pressure
sidered abnormal in pregnancy B. Oxygen saturation
C. Pregnancy is inadvisable in a woman C. Schober test
with CKD D. Signs and symptoms of heart failure
D. Pre-pregnancy counselling, multivita- E. Urine dipstick for proteinuriaAnswer: C
mins, management by a multidisciplinary 7. Concerning dialysis in a pregnant woman,
team, replacement of teratogenic drugs the following are true:
for pregnancy safe drugs improves A. Indications include maternal urea con-
outcomes centration is 10–15 mmol/L
E. Aspirin 75–150 mg from 12 weeks B. Pregnant women with acute kidney
reduces the risk of superimposed injury due to massive haemorrhagic
pre-eclampsia shock do not require dialysis
Answer: B C. AKI complicating HELLP syndrome
2. The obstetric risks of chronic kidney disease may benefit from early dialysis
in pregnancy include the following except: D. Increased frequency of dialysis is
A. Miscarriage required for patients on dialysis who get
B. Placental abruption pregnant
C. Postpartum haemorrhage E. Peritoneal dialysis is preferred over
D. Sepsis haemodialysis
Answer: B Answer: D
3. The maternal risks of chronic kidney disease 8. Individual risk factors for pre-eclampsia
in pregnancy include the following EXCEPT: include the following EXCEPT:
A. Depression A. Cervical cerclage
B. Gestational diabetes mellitus B. Hypertension
C. Mortality C. In vitro fertilization
D. Obesity 5. Wiles KS, Nelson-Piercy C, Bramham K. Reproductive

health and pregnancy in women with chronic kidney
E. Multiple pregnancy disease. Nat Rev Nephrol. 2018;14(3):165–84.
Answer: A 6. Wiles K, Chappell L, Clark K, et al. Clinical prac-
9. Complications of pre-eclampsia includes the tice guideline on pregnancy and renal disease. BMC
following EXCEPT: Nephrol. 2019;20:401.
7. Wiles K, et al. Serum creatinine in pregnancy: a sys-
A. Intrauterine foetal death tematic review. Kidney Int Rep. 2019;4:408–19.
B. Multi-organ failure 8. Piccoli G, Daidola G, Attini R, Parisi S, Fassio F,
C. Acute Kidney Injury Naretto C, Deagostini M, Castelluccia N, Ferraresi
D. HELLP Syndrome M, Roccatello D, Todros T. Kidney biopsy in
pregnancy: Evidence for counselling? A system-
E. Gestational diabetes mellitus atic narrative review. BJOG. 2013;120 https://doi.
Answer: E Gestational diabetes mellitus org/10.1111/1471-0528.12111.
10. Postnatal follow-up after pre-eclampsia 9. Brown MA, Magee LA, Kenny LC, et al. International
include the following EXCEPT: Society for the Study of Hypertension in Pregnancy
(ISSHP). The hypertensive disorders of pregnancy:
A. Blood pressure ISSHP classification, diagnosis & management rec-
B. Contraception ommendations for international practice. Pregnancy
C. Kidney function Hypertens. 2018;13:291–310.
D. Six minute test 10. Chappell LC, Duckworth S, Seed PT, et al. Diagnostic
accuracy of placental growth factor in women with
E. Urine dipstick for proteinuria suspected preeclampsia: a prospective multicentre
Answer: D study. Circulation. 2013;128:2121–31.
11. Gammill HS, Jeyabalan A. Acute renal fail-
Test your learning and check your understand- ure in pregnancy. Crit Care Med. 2005;33(Suppl
10):S372–84.
ing of this book’s contents: use the “Springer 12. Kristensen JH, Basit S, Wohlfahrt J, Damholt MB,
Nature Flashcards” app to access questions Boyd HA. Pre-eclampsia and risk of later kidney dis-
using https://sn.pub/cz9Cok. To use the app, ease: nationwide cohort study. BMJ. 2019;365:l1516.
please follow the instructions in Chap. 1. 13. Scully M, Thomas M, Underwood M, Watson
H, Langley K, Camilleri RS, Clark A, Creagh D,
Rayment R, Mcdonald V, Roy A, Evans G, McGuckin
S, Ni Ainle F, Maclean R, Lester W, Nash M, Scott
References R, Brien O. collaborators of the UK TTP Registry.
Thrombotic thrombocytopenic purpura and preg-
1. Dunlop W. Serial changes in renal haemodynam- nancy: presentation, management, and subsequent
ics during normal human pregnancy. Br J Obstet pregnancy outcomes. Blood. 2014;124(2):211–9.
Gynaecol. 1981;88(1):1–9. 14. Fyfe-Brown A, Clarke G, Nerenberg K, Chandra
2. August P. Preeclampsia: a “nephrocentric” view. Adv S, Jain V. Management of pregnancy-associated
Chronic Kidney Dis. 2013;20:280–6. thrombotic thrombocytopenia purpura. AJP reports.
3. Rolnik DL, et al. Aspirin versus placebo in pregnan- 2013;3(1):45–50.
cies at high risk for preterm preeclamspia. N Engl J 15. Kelly RJ, et al. Eculizumab in Pregnant Patients with
Med. 2017;377:613–22. Paroxysmal Nocturnal Hemoglobinuria. N Engl J
4. Magee LA, et al. CHIPS Study Group (2016). The Med. 2015;373:1032–9.
CHIPS Randomized Controlled Trial (Control 16. Bose P, Regan F, Paterson-Brown S. Improving
of Hypertension in Pregnancy Study): Is Severe the accuracy of estimated blood loss at obstetric
Hypertension Just an Elevated Blood Pressure? haemorrhage using clinical reconstructions. BJOG.
Hypertension. 2016 Nov;68(5):1153–9. 2006;113:919–24.
Transitional Care of Adolescents
and Young Adult Patients
25
with Kidney Disease
Joyce Popoola and Christopher Esezobor
Clinical Scenarios friends: caring for her kidney transplant on

(a) An 18-year-old female was seen in the adult top of this was overwhelming for her, and she
kidney transplant clinic. She had first devel- just didn’t feel that there was any support for
oped kidney disease due to haemolytic urae- people in her position: by the end of the aca-
mic syndrome five years prior to this, in demic year, her kidney allograft had failed,
Portugal. She had then spent 2 years on hae- and she was re-established on haemodialysis.
modialysis, before going on to receive a A stormy period restarting haemodialysis
deceased donor kidney transplant. At that ensued, as she suffered with recurrent infec-
time, she had excellent subsequent allograft tions, and challenges in keeping to her dialy-
function, reflected by a baseline serum cre- sis time slots. Recurrent hospital admissions
atinine of 90 μmol/L (1.02 mg/dL). At the age led her to defer her university studies. Multiple
of 16 years, she had relocated with her par- donor-specific antibodies proved a challenge
ents to the UK, maintaining her transplant to re-transplantation, but this was eventually
function with her new paediatric transplant achieved two years later, when her mother
clinic team. Now 18, she had recently started was able to donate a kidney via the kidney
university in a new city, away from her par- sharing scheme, and she received the same.
ents, and returned during the holidays to the She was able to return to university stud-
adult transplant clinic for her follow-up ies at the age of 22; this time living at home,
appointment. Her serum creatinine was and studying at a more local university.
found to be 203 μmol/L (2.3 mg/dL). Reflections:
She reported challenges combining her What support could have been offered to
university studies and keeping up with her this patient, and how could this have been
tailored along her timeline?
J. Popoola (*) How can periods of transition and their
Department of Nephrology and Transplantation, potential impact in a young person’s journey
be identified?
Trust, London, UK
(b) A 17-year-old male was preparing to trans-
fer his care to an adult kidney unit. He had
e-mail: joyce.popoola@stgeorges.nhs.uk
been born with prune belly syndrome: with
C. Esezobor
dysplastic kidneys, complicated by vesico-
Department of Paediatrics, Faculty of Clinical
Sciences, College of Medicine, University of Lagos, ureteral reflux, he had undergone extensive
Idi-Araba, Lagos, Nigeria reconstructive surgery at the age of
https://doi.org/10.1007/978-3-031-09131-5_25
506 J. Popoola and C. Esezobor
18 months. Despite this, he progressed to end the short time he had been in the city, he
stage kidney disease (ESKD) by the age of hadn’t registered with a primary care practi-
3 years. Having had extensive prior abdomi- tioner, and was advised to do so by the emer-
nal surgery, peritoneal dialysis was pre- gency team. A series of presentations to
cluded, so he was established on different medical services ensued—culminat-
haemodialysis via a tunnelled catheter. ing in blood tests—and his formal diagnosis
Neither of his parents were found to be suit- with chronic kidney disease CKD stage G4A3
able live donors, but he received a deceased secondary to IgA Nephropathy. His condi-
donor kidney transplant at the age of 5 years. tion progressed rapidly, rendering him dialy-
Most of his early education had been through sis-dependent within 6 months. He found
home-schooling, or within the hospital set- adherence to dialysis extremely challenging,
ting. From the age of 15 however, his kidney and was unable to establish a stable home in
transplant function declined, and he had the city. He suffered with significant mental
recently returned to haemodialysis, just prior health issues: he often found it difficult to
to his transition to the adult kidney unit. express himself, and would tend to walk
The patient and his parents displayed away from situations where he did not feel he
considerable anxiety over his prospective was getting the help he required. Just four-
move to adult care. They had visited several teen months after his diagnosis, he took his
kidney units across the region, and had even- own life.
tually opted for one where all young adults Reflections:
were being dialysed as a cohort. His transi- Could any interventions have helped to
tional journey was supported by a young change the outcome for this patient?
adult worker, who worked as part of his kid- At which time points in his timeline could
ney care team. His three-week gradual trans- interventions have been made?
fer of care, with regular dialysis sessions (d) A 13-year-old male South Western Nigerian
alternating between the paediatric and adult apprentice car mechanic presented to the
centres, took place until he felt sufficiently local government general hospital with a
established in a routine on the adult dialysis history of excessive tiredness. Investigations
unit. He received his second deceased donor showed he was Hepatitis B/HIV positive,
kidney transplant one year later, and—now with CKD Stage G5. He had never been sex-
aged 20—is finishing his first year at univer- ually active. He was an orphan, as his mother
sity, with stable allograft function. had died from an undiagnosed wasting ill-
Reflections: ness six years ago, and he had never known
What unique dynamic may present in a his father. He lived with his trainer as an
young adult, dependent on healthcare sys- unpaid servant to pay for his training. He
tems for their whole life? was triaged as an adult, in accordance with
How can parents and schooling alter this hospital guidelines, and was presented with
dynamic? a bill for the investigations that had been
(c) An 18-year-old male called the emergency undertaken so far. He had no financial means
services with generalised “tiredness”. He to pay this bill, let alone the costs of treating
had moved just weeks before from the north his condition.
of the country to London, in the UK—away Reflections:
from his mother—who had herself struggled How does this young person’s experience
with alcoholism following the breakdown of differ from what would apply in the devel-
her previous relationships, including with his oped countries?
father. In moving, he had been hoping to get What interventions could make a difference,
work to generate funds to attend College. In what limits may the environment present?
25 Transitional Care of Adolescents and Young Adult Patients with Kidney Disease 507
Introduction In this chapter, we will explore transitional

kidney care, and issues relating to young adults
Transitional care is a relatively neglected area and adolescents with acute, chronic and other
across all spheres of medicine: adolescents (aged kidney diseases as well as those requiring kidney
10–19 years) and young adults (aged 16–29 years) replacement therapy such as haemodialysis, peri-
are generally considered a ‘healthy group’—with- toneal dialysis and transplantation. Specific treat-
out significant healthcare issues. Traditional ments for individual pathologies have been
healthcare models have instead concentrated on outlined in other chapters in the book.
the extremes of age—with separate specialties for
Senior Health and Paediatrics, and further delin-
eations in care for neonates and infants: these Transitional Care
‘age-focused’ specialties have formed well-
structured care pathways, that are optimised for The most widely accepted definition of
their end-users, and their families. The group in Transitional Care is that of ‘a purposeful, planned
between are predominantly made up of adults of process that addresses the medical, psychosocial
the ‘middle-age’, who are cared for in general and and educational/vocational needs of adolescents
specialty medicine, and for whom specialty path- and young adults with chronic physical and med-
ways are more often targeted. Work over the last ical conditions, as they move from child-centred
decade has highlighted poorer outcomes, coupled to adult-orientated healthcare systems’ [3, 4].
with negative perceptions of healthcare amongst Perhaps most pertinently, this description empha-
this vulnerable group of young adult patients. sises the importance of the transition process
Older adolescents (aged 16–19 years) account starting well before the young person leaves the
for 36% of emergency department admissions, and care of children’s services.
20% of those receiving inpatient care under adult Paediatric specialties have a relatively high
medical services of all specialties in the UK [1]. staff-to-patient ratio, which can help to convey a
Kidney disease, which can manifest due to multi- sense amongst patients of more ‘individualised’
ple different factors, can complicate a significant care. An abrupt transfer from this individualised
proportion of these acute admissions. Furthermore, environment to adult care may elicit feelings of
an improved survival amongst infants and children abandonment in the young adult patient. Rather,
with complex metabolic diseases and congenital transfer of the young person’s care should begin
disorders, as well as small-for-dates and premature early, with an awareness that the process will
infants, has led to increased numbers of adolescent mirror their progression through school years. It
patients transferring from paediatric to adult ser- should be an enabling process, which normally
vices, again not infrequently complicated by kid- works best with a named key worker on both
ney disease. In developing countries, such as in children’s and adult healthcare sides. Ideally, dis-
Sub-Saharan Africa—where adolescents make up cussions should start from as early as ages nine to
about a quarter of the total population—an thirteen, and by the age of fourteen at the latest.
increased life expectancy of children with sickle Discussions should be focused on dealing
cell disease and HIV—which are significant risk with areas such as developing the young person’s
factors for developing CKD, means more children knowledge about their condition, their medica-
with CKD are surviving into adolescence, and tions, and dealing with any issues with concor-
thence into adulthood. When compared with other dance. Self-efficacy, personal responsibility and
adults, young people often report feeling less self-advocacy are important skills that young
involved, lower confidence and satisfaction with patients need to develop (Table 25.1). There is
their care, and less trust in their doctors. They also also an element of individualised judgement as to
tend to perceive that they are treated with less a young patient’s ‘transition-readiness’: As a
respect and dignity by staff than their younger, and standard, this should take place between the ages
older counterparts [2]. of fifteen to eighteen, although some cases may
Table 25.1 Stages of Transitional Care. Transition transfer into their chosen adult facility. The young person
should be a programmed progression through the various should be at the centre of this process; their family, carers
stages of the young person’s preparation, and subsequent and health professionals should be supportive in their role
Transition Stage* Targeted Age-Appropriate Intervention

Stage 1 (12 - 13 • Young person and family are introduced to the idea of transition
years) to adult health care, ideally at their local unit
Stage 2 (14 - 15 • Young person and family are given more detailed information on
years) the transition process
• Team begin to pass on skills required to enable self-care
Stage 3 (16 - 17 • Young person should become confident in self-care (self-efficacy),
years) able to ask for help required (self-advocacy), but requiring
minimal input from their support network
• Confidence in their ability is critical at this stage
Stage 4 (16 – 21 • Young person is about to be or is already fully integrated into
years) adult services, and able to function independently in the
management of their kidney disease, or kidney replacement
therapy
*
In settings where the transfer of adolescents to adult services occurs earlier, the proposed interventions
should occur at an earlier age.
require longer in the paediatric setting—particu- voice in a section of society. For the adolescent
larly those young adults with significant learningand young adult, transition occurs at a time when
difficulties, or who display challenging behav- they are seeking their individual identity and
iour [4–6], others may require shorter period voice—but are moved from one healthcare set-
where administrative measures stipulate transi- ting, in which they may feel at the centre of atten-
tion to adult services at a younger age. tion, and be seen as role-models to their peers—to
There are multiple tools and guidelines avail-another, in which they are no longer the centre of
able, all of which reflect a stepwise approach, attention, with few peers of their age. It is of no
rather than abrupt transfer when followed, to pro-surprise then, that young people’s perceptions of
vide the desired outcome for the young person healthcare are of being insignificant and unim-
[4–6]. Lack of interaction between the children’s portant, with no time or space given for their
and adult centres tends to be the main hindrance opinions to be heard or needs to be met.
in implementation, with despite understanding We should also highlight the important physi-
this process and the plethora of recent policy ological developmental changes that occur dur-
statements, transitioning to adult renal care is ing adolescence and young adulthood:
poorly coordinated, often delayed, and usually characterised in particular by the physical, neuro-
managed through a single referral letter, making logical and emotional developmental changes
it a challenge for the young person to engage. associated with puberty and beyond [7, 8].
Adolescents and young adults are thus especially
vulnerable—due both to potential disjunction in
What Makes Healthcare a developing brain, and behavioural and cogni-
for the Young Adult Population tive systems that mature over different times-
Different? cales, and concurrently contend with the control
of common independent biological processes,
The majority of patients engaging with hospital including sexual maturation [9]. Cognitive devel-
services outside of paediatrics are the middle- opment between childhood and adulthood may
aged and the elderly. As in most walks of life, be briefly summarised by the development of
majority groups tend to become the dominant abstract thinking from concrete operational
Table 25.2 Outline of the aspects of care which de-novo into adult services. The arbitrary split into
require identification and attention in the young adult health, social and developmental factors may help ensure
transitioning from the paediatric unit or transferring that all aspects of care of the young adult are dealt with
Health Social Development

Medication Concordance Social isolation Transition
Clinic non-attendance Smoking Education
Diagnosis awareness Alcohol issues Independence skills
Health Education Recreational Drugs Behaviour & Emotions
Physical activity Housing Restricting disabilities
Dietary Habits Immigration Employment
Sexual Health Abuse Finance
thought processes: Abstract thinking is the ability behavioural state of each young adult, regardless
to consider concepts, make generalizations, and of their chronological age. Developing a picture
think philosophically; Concrete thinking is a nec- of each young person is also essential through
essary first step in understanding abstract ideas: awareness of the various spheres impacting their
First, we observe and consider what our experi- life at a particular point in their life journey.
ences are telling us, and then we generalize, and These could be combinations of health, social or
build on our experiences, using these to self- developmental related factors with varying domi-
regulate appropriately. Development of abstract nance over time (Table 25.2).
thinking may alternatively be described as the
ability to move away from seeing individual
actions and the whole world as either black or hat Makes Adolescents and Young
W
white [10]. Adults on the Kidney Unit Different?
As these important stages in cognitive devel-
opment occur during adolescence and young In addition to all the normal influences on their
adulthood, the perspectives and behaviours of the lives, adolescents and young adults with kidney
young person become far more understandable. disease are also challenged with adapting to life
A common example is around medication with chronic kidney disease, or kidney replace-
concordance: ment therapy via haemodialysis, peritoneal dialy-
“I’ve done really well—I have been good all this sis, or kidney transplantation. Depending on the
week because I took all of my medications. What’s aetiology and their stage of kidney disease, they
the big deal if I missed a few doses because I was may have significant dietary and fluid restric-
out with my friends—they tell me I’m no fun ‘cos tions, a large number of medications to take each
I’m always fussing over my meds”
day—and with medication concordance being
With maturity, more developed abstract thought absolutely critical in particular following a kid-
processes may supersede the more basic ‘con- ney transplant [12]. Each young person may
crete’ observational thought processes, and the additionally be at a different critical period of
young person may come to the realisation that their social and emotional development—such as
they need to be wary of advice from their current making key relationships, going through educa-
company if they are not supportive of their self- tional changes, leaving home, all of which must
care. They may also start to recognise that miss- fit alongside the additional lifestyle changes
ing tablets regularly may have long-term required by their kidney disease (Fig. 25.1).
detrimental effects on their health [11]. Adolescents and Young Adults may present to
Taking the relative maturity of the young per- the adult kidney unit as a direct transition from
son’s thinking into account can make the their paediatric unit, or as a new referral:
approach for negotiation far clearer. Boundary- Depending on the aetiology of their kidney dis-
setting has to take into account the emotional and ease, they may merely require regular monitoring
Hospital FAMILY
RELATION- FRIENDS
Admissions SHIPS
WORK
SOCIAL
Outpatient LIFE
Clinic Visits
Young Adult
HOUSING
LIFE
HEALTH
Surgery
IDENTITY
UNIVERSITY
SEXUALITY
Food and EMOTIONS
Fluid
Restriction
Medication
Fig. 25.1 The Impact of Kidney Disease on a Young adulthood (turquoise), and the additional factors that can
Adult Life. Bubble diagram illustrating factors influenc- impact the life of a young adult with kidney disease (blue)
ing the life of a typical adolescent moving into young
with a mixture of supportive and medical man- Non-adherence with kidney transplant medications
agement [13]. Their kidney function may alterna- amongst young adults, for instance, is four times
tively be on a trajectory heading toward end stage greater than in the general adult. Failure to engage
kidney disease, and the need for kidney replace- properly with adult services has been shown to be
ment therapy (KRT). The young person may associated with increased morbidity [17, 18].
already be on kidney replacement therapy: the
majority (73%) in this group will have a func-
tioning kidney transplant, although up to 35% of ow Can We Improve Outcomes
H
young adults lose a successfully functioning kid- for Young People in the Kidney
ney transplant within 36 months of moving to Unit?
adult services—this is a significantly increased
rate of allograft loss compared with children and Tailored psychological and social support is
older adults [14]. required, alongside direct medical care of their
Young people are particularly aware of their kidney disease, and any other co-morbidities, and
body image, hence peritoneal dialysis and hae- support for them when they are acutely unwell.
modialysis catheters, arteriovenous fistulae, and Interestingly, young kidney patient and healthcare
the impact of fluid retention and medications workers’ perspectives as to the impact of kidney
such as steroids and calcineurin inhibitors, which disease do differ markedly: A survey of over a 100
are all such clear and common clinical signs in young adults with kidney disease carried out at St
kidney medicine—can also compound a young George’s Hospital reported keeping active &
kidney patient’s frustrations [15]. exercising, limits on food & drink, and going out
Adolescents and young adults are thus twice as with friends as their top three major challenges.
likely to demonstrate concordance issues when By contrast, their caring healthcare workers felt
compared with the wider adult population [16]. that Limits on food and drink, attending dialysis
Table 25.3 Perceptions of Challenges to Daily Living for Young Adult Patients with Kidney Disease. Breakdown
of the top three challenges to daily living reported by young adult patients with kidney disease, compared with perceived
limitations reported by caring staff, and age-matched medical students. Aspects of medical care and issues directly
related to their clinical condition were relatively low on their priority list even though they were perceived by health
care workers as a priority for the young adults
Rank Young Adult Patients Caring Staff Age-matched Medical

with Kidney Disease Students
1 Keeping active & Limits on food and Attending dialysis
exercising drink
2 Limits on food and drink Attending dialysis Limits on food and drink
3 Going out with friends Attending hospital Attending hospital
appointments appointments; spending time
with friends
and hospital appointments were their three big- readmission, and shortening hospital stays, since
gest challenges (Table 25.3). Whilst both lists dis- young people with kidney disease are likely to
play an awareness of the patients’ loss of spend a considerable proportion of their life in
autonomy, it highlights the importance of identi- and around healthcare settings.
fying and helping to address patient reported fac- The young person may require additional sup-
tors, rather than merely staff perceptions. port around procedures such as surgery, dialysis
In order to achieve full engagement with their catheter insertions and investigations.
direct medical care, young adults require mental, Establishing a link surgeon, and anaesthetists
emotional and social support, to enable them with experience in dealing with young people
manage their physical and medical needs [19]. and children can be invaluable, in particular to
The way in which young adults present to adult deal with the slight nuances required to consent,
service, and their subsequent management can where the next of kin, or an alternative indepen-
make a profound impact on their short, medium dent witness may be required where a patient
and long-term outcomes. Planning and support lacks competence to consent. Of course, there are
therefore needs to take into account whether the other situations in which an adolescent under 16
young person has presented directly to adult ser- years of age may be deemed competent to con-
vices as an acute admission or via clinic, or as a sent through Gillick or Fraser competence.
planned transfer from paediatric services. Nursing staff and other members of the multi-
Embracing a methodical approach, such as disciplinary team need to be educated, and be
embracing a toolkit to guide their care can help provided with the tools around the nuances of
provide a structure, and uniformity of approach caring for and supporting young persons in kid-
(Table 25.4). ney units. An invaluable addition to the work-
Young persons are likely to need additional force is a Young Adult Worker, and identification
support in order to minimise hospital admissions, of a Transition and Young Adult Consultant lead.
since not understanding their perspective can It is beneficial if the latter has experience in pae-
lead to prolonged inpatient stays, particularly if diatrics to facilitate as seamless a transition as
they are perceived as not co-operating, and the possible.
quality of communication is poor, or even absent. Young adult workers (YAW) can offer an
Discharge planning for a young adult requires invaluable resource: when available, they should
early reflection, as it is not uncommon for them be involved in every aspect of the young persons’
to have complex discharge needs, particularly as pathway—for instance in their inpatient stay and
they may have concomitant long term disabili- discharge planning (Appendix 1). They serve as
ties, and other social and/or mental health con- the advocate and a liaison across the various spe-
cerns. Emphasis needs to be given to preventing cialties particularly to help overcome the young
Table 25.4 A Toolkit for Transitional Care. The elements required to ensure a smooth and effective transition from
paediatric to adult services
Toolkit Tool Components

Care Plan • Detail of young person’s care needs, who will support them in the adult
service
• Young person should be involved in service, design, delivery and
evaluation
• Focus should be what is possible for the young adult
Personal Folder • One page profile (or portable, accessible electronic summary)
• Information about health condition & medications
• History of unplanned admissions
• Preferences about parent/carer involvement
• Emergency care plans
• Strengths, achievements, hopes for the future and goals
Young Adult • Works with young adult in adult service to help them use the service
Worker • Explore alternative ways to help the Young Person meet their care
needs early on
General or • All young adults must be registered with a medical practitioner in the
Family community
Practitioner • Especially important to review if young adult has moved
• Central point for prescription medications
Identified • Family, carers, social workers, members of educational institutions etc
Community
Support
network
person’s challenges around articulating their important to bear in mind that young adults may
needs, with a view to ultimately enabling self- themselves have young dependent children, or
empowerment of the young adult. The YAW pro- have independent carers where this is required, or
vides 1:1 support tailored to the individual young require additional reasonable adjustments to take
person they are able to relate in a maturity appro- account of their individual disabilities.
priate way to the young person and provide con- Adherence and concordance to treatment
tinuity of care. They also assist in co-ordinating schedules often requires innovation—for instance
appointments, investigations, support in the com- charts, medication cards, electronic reminders,
munity, as well as create social opportunities dosette boxes or blister packs, one-on-one train-
through buddies and peer support networks. They ing sessions with a pharmacist to talk about each
signpost the young person to educational and of their medications, the involvement of a ‘buddy’
career opportunities: interview/application/grant (peer support), and other members of their sup-
opportunities as young people with kidney dis- port network [11].
ease often miss schooling and examinations, Establishing integrated paediatric and young
leading to poor performance, which can prevent adult clinics are an important aspect of young
them from reaching their educational goals, and adult services. Such dedicated clinics promote
thus limit their career potential. Social Support more engaged young adults and provide the
Services maybe required—this is often practical opportunity for the young adults to be seen in the
to assist the young person with daily living, sort- same clinic. They work best where they incorpo-
ing out benefits, housing and social support. It is rate named members of the multidisciplinary
team as this enables continuity and more focused ing home environment. The many difficulties of
care of young people in a youth friendly sup- bringing up a child with a chronic illness may not
ported environment [20]. The Young adult clinic infrequently lead to the breakdown of the family
provides a unique opportunity to break down unit—such that young adult patients may live in a
feelings of isolation and promote support net- single-parent home. Financial strain is also com-
works, as the attendees are more likely to meet mon—consequent upon both the added expense
contemporaries when they are seen as a cohort. of supporting young adult patients, and because
Harnessing peer support can also have a posi- carers may be have to give up gainful employ-
tive impact on adherence to treatments such as ment, or work flexibly around the young person’s
dialysis for instance cohorting young adults on needs. There are also situations where care is pro-
the same shift. The provision of peer support with vided either wholly or in combination with a care
other young adults for instance on dialysis leads institution: whilst this may be associated with
to improved adherence to scheduled treatment greater costs for a family, and create a more con-
and improved wellbeing [21]. There is a need to fusing and unstable home environment for the
be mindful that peer pressure can cause emo- young adult patient, careful work to mitigate for
tional upheaval, which can be from other young these aspects may provide an optimal long-term
adults a partner and a desire to form intimate care environment for patients.
relationships, family (parents, siblings), lectures Feelings of inadequacy can arise in caregivers,
or teachers or friends. Provision of emotional as they not only negotiate the milestones of nor-
support is best achieved by discussing issues with mal transition from childhood to adulthood,
the young adults as they arise before they evolve. alongside other competing life events, but are
The young adult with disabilities such as deaf- also faced with the challenges of caring for a
ness, blindness, mobility issues, or learning dif- child with chronic illness: overseeing the daily
ficulties may require additional support—as may administration of medications, supporting
those whose parental culture or language may patients through procedures and treatments,
present a challenge to their receiving optimal attending other hospital appointments, and acting
healthcare. as patient advocate—all whilst maintaining an
outwardly positive outlook. Concurrently, they
may experience conflicts around letting go,
I mpact of Young Adult Care enabling and allowing the young person to transi-
and Transition on Caregivers tion into adult life, and developing the skills
required for independent self-care.
As resources are channelled into the care of Where clinical staff may witness individual
young people, it is important that the central role challenging episodes from a young adult patient,
of family, caregivers, and supporters is also high- caregivers may by contrast experience constant,
lighted: whilst healthcare providers may experi- sometimes bewildering outbursts or challenging
ence snapshots of a young adult’s clinical behaviours—the cause of which may not be
presentation, caregivers are closely involved in clear: caregivers frequently know best how to
the day-to-day support of the individual: in cer- manage these situations, and in a similar way,
tain circumstances, this can be unrelenting and should be recognised as key players in working
stressful, particularly in situations where the out how to achieve the best outcome for the
young adult patient has cognitive, behavioural, young person—whilst adopting a passive, or
mental health and/or significant physical more active role over the course of the young per-
disabilities. son’s care.
Young persons with kidney disease may have Caregivers may themselves require support,
siblings: competition between siblings for atten- and they should be signposted as to how to obtain
tion, parental feelings of guilt, overlaid with it accordingly: this may include receiving direct
other negative emotions, can lead to a challeng- support from a psychologist, and/or a social
worker—for their own personal care, beyond that paediatric and adult nephrology specialists—to
of the young adult patient. There may also be the ensure that the best care is provided to this vul-
need to help enable caregivers to apply for grants nerable group. The aim should be that despite the
and other sources of financial support, to help the presence of a chronic medical condition, the
young adult patients and their families cope. young person should, in addition to being pro-
Similarly to their charges, caregivers may also vided with age-appropriate medical care, be
benefit from peer support or ‘buddying’, to help enabled to reach their maximal potential socially,
them work out solutions to every-day challenges. mentally and emotionally, whilst minimising
The importance of facilitating a healthy morbidity and mortality.
dynamic—not only for the young adult patient, but
also their caregivers—cannot be overemphasised.
Practice Points
lobal Perspectives of Young Adult

G • Liaise closely with your paediatric
Care and Transition nephrology colleagues to ensure that
adolescent and young adult kidney
The provision of healthcare varies enormously patients are engaged in the transition
across the world: this has led to enormous gaps in process early
healthcare provision for large sectors of soci- • Get to know who the different members
ety—which are particularly marked in develop- of the transition team in your kidney
ing nations, and are reflected in healthcare unit are
outcomes when comparing developed and devel- • Identify all additional members of your
oping nations. patient’s support network
Financial allocation for healthcare are com- • Agree sensible, achievable therapeutic
plex and multi-layered: very young <16 years goals with your adolescent/young adult
(paediatrics) and older >65 years (geriatrics) kidney patient
patients frequently have dedicated services to • Some adolescent/young adult kidney
support them; the majority of general care is patients, presenting directly to adult kid-
geared towards the middle aged (40–65), who ney services, may also benefit from ded-
constitute the highest number using healthcare icated and coordinated support from a
resources. The majority of funds are deployed to young adult team
treat older patients in developed nations, where
there is a higher age expectancy, culminating in
better survival, with increased numbers of co-
morbidities amongst this demographic. Conclusions
The idea of medical care specifically catering
for young adults is a relatively undescribed area, It is useful to reflect on the four very different
with little targeted funding or legislation, even in clinical scenarios from the beginning of the chap-
some of the more developed nations. In the conti- ter—each very complex in nature. Both cases A
nents of Asia and Africa, care for young adults and B were well-known to their respective paedi-
constitutes even more of an enigma: there is sig- atric nephrology teams, but patient A’s transition
nificant variation in practice: the definition of an was complicated by her move to a new country,
adult for timing of transition is as young as and subsequently starting higher education in a
12 years in some developing nations, 16 years in new university environment, away from home.
parts of North America [22], and 18 years in most This led to a loss of continuity in support, and
parts of Europe. To overcome the shortfall of tar- co-incident failure of her kidney allograft—with
geted care for this patient group, it is important a heavy cost in terms of a deferment in her uni-
that there is enhanced cross-working between versity education of four years, and a clinical
pathway complicated by infection on resumption ppendix 1: The Transitional Care

A
of dialysis. Patient B’s carefully planned approach Referral Form
to transition, and adapted educational support
throughout his childhood, allowed for a smoother A sample referral form for the transfer of care of
pathway to a second transplant, and resumption a young adult from paediatric to adult kidney
of his university education. Patient C’s devastat- services
ing story reflects the bold intentions of a young REFERRAL FORM FOR YOUNG ADULT
man attempting independently to find a construc- KIDNEY PATIENTS TO TRANSITIONAL
tive pathway out of a mutually physically and CARE
emotionally erosive life at home. Complicated by
end stage kidney disease, and the absence of an Demographics
Name:
available support network—and without the
Date of birth:
engagement of dedicated young adult or mental Ethnicity:
health services, his life on kidney replacement Religion (Spiritual beliefs):
therapy rapidly spiralled downward, culminating Medical Problems
in him taking his own life. Patient D’s case high- Renal Diagnosis
Other relevant co-morbidities
lights the vast difference in health care access, Renal Status
and differing definitions as to who is a competent Transplant
adult, and thus who is responsible for his care. Peritoneal dialysis
The 13-year-old being treated as an adult, with no Haemodialysis
healthcare insurance, has huge—potentially life- Relevant Social Issues (and key worker where
relevant)
limiting implications on his morbidity and mor- Relevant Psychological Issues (and key worker
tality: this is the story of many, particularly in the where relevant)
developing world. Disabilities or learning difficulties (and key worker
The issues around transitional care for ado- where relevant)
lescent and young adult kidney patients have
only relatively recently been highlighted, par-
ticularly by inferior clinical outcomes and Questions
engagement when compared with adult care.
Improving awareness of the common issues,
and identifying collective solutions can go a 1. According to the World Health Organisation,
long way to addressing these—in the UK, the adolescents make up which age group?
Department of Health (DOH), the National A. 10–15 years
Institute for Health and Care Excellence (NICE) B. 10–19 years
and the Care Quality Commission (CQC) all C. 11–21 years
support a model that provides a tailored, patient- D. 16–29 years
centred service, led by a multi-disciplinary E. 15–21 years
team. We might optimally call for this model to Answer B: Whilst there are arguments that ado-
include adult and paediatric nephrologists, lescence should encompass the mid 20’s, the
trained nurse specialists, and all other members World Health Organisation (WHO) defines
of the multidisciplinary kidney care team, coor- adolescence as 10–19 years. Those age between
dinated by a dedicated young adult worker, 15 and 24 are regarded as ‘Youth’ and ‘Young
liaising closely with each other, the patient and People’ covers those between 10 and 24 years.
their individual care network, with the shared A. False
goal of providing holistic, mutually satisfying B. True
care, incorporating physical, mental and social C. False
health—both throughout transition, and into the D. False
patient’s adult life beyond this. E. False
2. An 18 year old female with end stage kidney lowing the divorce of his parents. Which of
disease secondary to IgA nephropathy is the following need to be taken into consider-
referred to the adult transplant follow up ation following his transfer to a new renal
clinic 1 year following her deceased donor unit?
transplant. Her baseline serum creatinine is A. Paid employment
90 μmol/L (1.02 mg/dL), and her urinalysis B. Social isolation
remains negative for protein and blood. C. Independent living
Which of the following is true? D. Educational opportunities
A. The risk of recurrence of IgA nephropa- E. All of the above
thy in her transplant kidney is 3% Answer E: Despite this young man having
B. The risk of her losing her kidney allograft plans of living independently he may not
in the next three years is up to around have means or the awareness and may have
35% in fact been dependent on one or both of his
C. Her risk of graft failure would be signifi- parents for support in managing his medical
cantly reduced if she had been trans- condition. At his initial consultation it would
planted at a younger age be essential to take a holistic approach to his
D. She should be followed up on an annual care exploring whether he is prepared for
basis in the kidney transplant clinic independent living in the community in addi-
E. The likelihood of her kidney allograft tion to his ability to take responsibility for
remaining functional at 5 years is 98% his medical condition.
Answer B: The risk of her losing her kidney 4. What age should the transition process ide-
allograft in the next three years is up to 35% ally start for the young person moving from
A. False. The risk of recurrence of IgA paediatric services to adult services consid-
nephropathy in the graft is 6–20%, ering WHO guidelines from the choices
although may be as high as 58% depend- below
ing on the rate of biopsy and the length of A. 14 years
follow-up. The risk of graft loss due to B. 15 years
recurrent IgAN is 1.6–16% C. 16 years
B. True. The risk of young adult kidney D. 17 years
transplant recipients losing their kidney E. 18 years
allograft within three years of transition- Answer A: Transition should be a seamless pro-
ing to adult services is up to around 35% cess not only for the young person concerned
C. False. Her risk of graft failure is not but also for the caregivers and healthcare
altered by age at transplantation professionals. This can only be achieved if
D. False. UK Kidney association clinical the transition process starts early in the path-
practice guidelines suggest 3–6 monthly way of the young adult with chronic illness
follow up after 12 months—this may in order that they becoming familiar and
need to be adapted to the individual don’t feel isolated in their journey through
patient setting. healthcare systems. In order to achieve the
E. The likelihood of her kidney allograft preparation and transition process needs to
remaining functional at 5 years is 75% start as early as possible sometimes this can
post deceased donor transplantation, be as early as 12 years.
although it may be lower than 65% (see 5. The following need to be taken in to consid-
B). eration in relation to the registered carer if
3. An eighteen-year-old, Caucasian male with they are the parent of a transitioned eighteen-
CKD Stage 3 due to IgA Nephropathy has year old autistic adult with renal disease who
moved from the North of England to London is wheelchair bound with multiple disabili-
as he is keen to make his own way in life fol- ties with the exception of.
A. Has the ability to care for the young the local university and turns up for an emer-
person gency review in your clinic complaining of
B. Is willing to care for the young person abdominal pain over the transplant feeling
beyond 18 years tired and haematuria. The creatinine has
C. Tertiary Education of the carer gone from her baseline of 1.1 mg/dL to
D. Works or plans to do so 2.3 mg/dL (97 μmol/L to 204 μmol/L). You
E. Training in communication skills have never seen her before although this is
Answer C: Carers need to be adequately her second semester at the university. High
equipped even if they are the parents of a on your differential diagnosis must include
child. It should not be assumed that they have A. Urinary tract infection
the ability or will be the carers of the child B. Acute rejection
after the age of 18 years particularly in situa- C. Direct Trauma
tions where the child has complex needs. D. Recurrent disease
There are some environments where there is E. Chronic Allograft Nephropathy
not the infrastructure to meet such a young Answer B: Rejection must be high on the list of
person’s needs and this may require focus in differentials and quickly diagnosed or
the future as more infants with complex excluded due to the potential consequences
needs are starting to survive in to adult hood. of undiagnosed rejection and the fact that if
Provision of tertiary care such as university detected early it is reversible. Often a further
education to the carer is not a direct support history around adherence can assist with
to the young person’s care. making the diagnosis. Transplant loss in
6. A fifteen-year old secondary school student young people in transition phases for instance
presents to the Accident and Emergency hospitals and education is common particu-
department while on a day trip in Wales with larly when appropriate checks and balances
severe abdominal pain, she has acute kidney are not implemented to assist prevention.
injury and an obstructing renal calculus. 8. Which of the following is the most common
Who of the following cannot give consent for concern among adolescent and young adults
surgery. with renal conditions?
A. The parents A. Taking medications
B. The legal guardian B. Social networks
C. The student C. Educational opportunities
D. None of the above D. Dietary restrictions
E. All of the above E. The nature of their renal disease
Answer D: All of the listed can give consent for Answer B: Interestingly healthcare providers
the procedure including the young person in have very different perspectives to what is
the event they are considered mature enough to most important for young adults and their
understand the process and potential risks and general wellbeing. While maintaining social
benefit. This is through Gillick Competence a networks with friends is the predominant
term used in medical law to determine if a child concern of young adults, healthcare profes-
less than sixteen can consent independently to sionals seem tend to assume that the health
their medical care. In circumstance where this condition of the young adults is their pre-
is not possible due to for instance disability or dominant concern.
immaturity and neither parents or legal guard- 9. One of your young adults—a 23-year-old
ians are available consent be provided by medi- Indo-Asian female—recently got married,
cal professionals in an emergency by making following her diagnosis of lupus one month
the young person a ward of the court. earlier. She has been started on mycopheno-
7. A twenty-one-year old with a live donor late mofetil (MMF) and steroids, and is start-
transplant from her Father 5 years ago attends ing to show good response. She is keen to
start a family straight away, as she is being 11. The following strategies can be used to pro-
subjected to pressure from both her parents mote medication adherence among young
and her in laws. How would you manage her adults
case? A. Reduction of bill burden
A. Do nothing B. Highlighting potential side effects prior
B. Stop the immunosuppressive therapy to prescribing
C. Change her immunosuppression therapy C. Use of a dossette box or blister pack
immediately D. Enlisting a buddy or peer supporter
D. Refer for preconception counselling E. All of the above
E. None of the above Answer E: Adherence is an age old problem
Answer D: It is common to receive queries and one of the commonest causes of poor
from young adults hoping to get pregnant on response to treatment. All of the above strate-
potential teratogenic agents, in this case gies can be adopted other strategies include
mycophenolate mofetil. This patient is start- setting alarms, using electronic pill counters
ing to respond to therapy and we would nor- for monitoring. Ideally the aim of the transi-
mally aim for the lupus to stabilise prior to tion years is to reduce the dependence on the
pregnancy. Preconception counselling can carer so avoiding strategies that depend on
prove invaluable particularly if it involves the guardian to maintain adherence should
the partner, as it is an opportunity to make as be avoided.
safe a planned pregnancy as possible, with 12. One of your young adults—a nineteen-year-
improved concordance consequent upon an old male, had been hoping to receive a pre-
improved understanding, and ultimately pro- emptive renal transplant from his mother.
viding an optimal outcome for the young Unfortunately, his mother was found to have
person, and their chances of a successful a low GFR 59 and cystic changes to one of
pregnancy with minimal complications. her kidneys. The mother is insistent that she
10. A Young Adult Worker can take on the fol- donate to help her son regardless, as she
lowing roles except would do anything for her child. The follow-
A. Advocacy for young people ing would be the least appropriate approach:
B. Prescribing for young people A. Explore potential interim dialysis options
C. Enpowerment of young people B. Activate on the deceased transplant wait-
D. Creation of peer support opportunities ing list
for young people C. Arrange referral of mother to donor
E. Support co-ordination of clinics for surgeon
young people D. Explore other potential donors
Answer B: It would be unusual for a young adult E. Arrange counselling for patient and
worker to take on the role of prescribing medi- mother
cations for young people unless they had spe- Answer C: Where the care of young people is
cific training from another role which they concerned, it is not uncommon for parents or
carried a license for. A young adult worker has carers to want to take the place of their child in
a supportive role assisting the transition of the relation to the young person’s illness. In this
young adult and their subsequent care with in situation the mother would not be the best
the adult facility with the aim that the young donor for her son: for a young person, the
person is not inhibited from reaching their ideal donor offers as healthy a donor organ as
maximal potential in all spheres of life despite possible: additionally, it would lead her toward
their medical condition. a more significant renal impairment, which
could culminate in ESKD. Counselling, and 11. Popoola J, Greene H, Kyegombe M, MacPhee
IA. Patient involvement in selection of immunosup-
in some cases psychological input can have a pressive regimen following transplantation. Patient
vital role to help deal with feelings of guilt Preference and Adherence. 2014;8:1705–12.
and disappointment. 12. Watson AR. Non-compliance and transfer from pae-
diatric to adult transplant unit. Paediatr Nephrol.
2000;14:469–72.
Test your learning and check your understand- 13. Lost in transition: moving young people between
ing of this book’s contents: use the “Springer child and adult health services; RCN 2008.
Nature Flashcards” app to access questions using 14. Foster BJ. Heightened graft failure risk during emerg-
https://sn.pub/cz9Cok. To use the app, please fol- ing adulthood and transition to adult care. Pediatr
Nephrol. 2015;30:567–76.
low the instructions in Chap. 1. 15. Hamilton AJ, Casula A, Ben-Shlomo Y, et al. The
clinical epidemiology of young adults starting renal
replacement therapy in the UK: presentation, manage-
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Conservative Care for Patients
with Chronic Kidney Disease
26
Helen Alston and Katie Vinen
Clinical Scenario dialysis out-weigh the benefits. An alternative,

An 85 year old man is seen in the advanced kid- non-dialysis care pathway has therefore been
ney care clinic. He has an eGFR of 14 mL/ developed, called Conservative Care (CC).
min/1.73 m2 which is falling by 2 mL/min/1.73 m2 Comprehensive Conservative kidney care can
per year and a serum albumin of 30 g/L. He can be defined as planned, holistic, patient centered
walk 200 m slowly, but needs a stick to help with care for those with stage 5 chronic kidney dis-
balance. He meets friends weekly to play bowls ease, that does not involve kidney replacement
and is a keen gardener, although now needs help therapy (KRT). It includes interventions to delay
with this. He enjoys a good quality of life though progression of the disease and minimise compli-
his wife has disabling dementia. He has two chil- cations, but focuses predominantly on: manage-
dren and five grandchildren, two of whom live ment of symptoms; psychological, social,
abroad. His daughter has noticed some early cultural, and spiritual support; and advance care
memory difficulties. He has recently transferred planning [1, 2].
to the Advanced Kidney Care Clinic so that he This chapter aims to describe:
“can prepare for dialysis when the time comes”.
• key elements of the conservative care pathway
for patients with CKD
Introduction • approaches to assessment, and when this path-
way may be appropriate
What is Conservative Care? • tools to aid optimal delivery of this pathway.
When first developed, dialysis was offered only We acknowledge the relative paucity of data in
to young non-diabetic patients. As it became this area, and therefore highlight a practical
clear that it could benefit many other patients, in approach to delivering CC. We note key areas of
countries where resources allow, it was extended knowledge which are currently being actively
to older complex patients, including those over researched, supported by patients who see CC as
70. Whilst many benefit, for others the burdens of a top research priority.
H. Alston · K. Vinen (*)

Kings College Hospital NHS Foundation Trust,
London, UK
e-mail: helen.alston@nhs.net; katie.vinen@nhs.net
https://doi.org/10.1007/978-3-031-09131-5_26
522 H. Alston and K. Vinen
hy do we Require a Conservative
W central Europe (95%, 18/19), Oceania and South
Care Pathway? East Asia (93%, 14/15), western Europe (90%,
18/20), the Middle East (82%, 9/11), and Africa
In high income countries (all treatment options (80%, 33/41). However, CC was offered by fewer
for CKD 5 available): Choice driven conserva- than half of countries in Latin America (44%,
tive care: 8/18), and just over half of countries in newly
In high income countries, the development of independent states, Russia (57%, 4/7) and North
CC is a response to changing demographics of America (67%, 6/9).
the end-stage kidney disease (ESKD) population. Although some provision of CC was provided
Many patients are older or highly co-morbid, and at similar levels (75-85%) in countries of all
may benefit from or choose to have care which income levels, the provision of medically advised
avoids the burdens and medicalisation associated CC did rise with income level. Income also
with KRT. Care may involve a combination of appeared to affect the elements of CC that were
nephrological, care of elderly and palliative offered; only 37% of 154 countries offering CC
input. adopted a multidisciplinary team approach and
Improved treatments have also supported only 26% used shared decision-making tools
another population of patients (some relatively (e.g. practice guidelines for providers and patient
young) who begin dialysis in good health, but decision aids). Whilst systematic symptom man-
over years of treatment become frailer. Their agement of advanced kidney failure was provided
care may change to focus on symptom control, in 52% of countries, only 29% were able to pro-
reduced tablet burden and sometimes reduced vide psychological, cultural, and spiritual support
dialysis frequency. Care focuses on maintaining within CC.
quality of life and planning for end-of-life.
These interventions overlap CC but are deliv-
ered in parallel with KRT—this is often called hat Are the Key Elements
W
supportive care but is outside the scope of this of the Conservative Care Pathway?
chapter.
In middle and lower income countries Whilst the key elements of comprehensive CC
(treatment choices may be restricted): Choice are defined, their relative importance varies over
restricted conservative care: time and, even in affluent health systems, there
In lower income countries, CC may be offered remains variation in elements of the pathway
as a choice-restricted option when resources do offered.
not allow provision of KRT for all patients. Here Where choice-driven CC is provided, early
the population receiving CC may be younger, with priorities include honest prognostic informa-
fewer co-morbidities. Where resources are lim- tion, excellent communication, and understand-
ited, only certain aspects of CC may be available. ing the patient’s own beliefs and wishes.
Preservation of function (physical, cognitive
and renal), excellent symptom control, reduc-
ariations in Conservative Care
V tion in treatment burdens (including maximising
Provision hospital-free days), and an effective network of
professional support can then be offered.
In 2019, an ISN global survey on care for ESKD Ensuring a “good death” and providing support
found that CC was offered in 124 (81%) of 154 for family before and after death are important
countries [3]. In 66 countries (43%), this option later aspects of CC.
was choice-restricted, whilst in 77 (50%) countries, In countries only able to offer choice-restricted
CC availability was driven by patients’ choice or CC, the focus of resources will be less on sup-
medical guidance, and not limited by resources. porting decision-making, and more on later
CC was offered in all countries in north, east, aspects such as symptom control. Key elements
and south Asia, and most countries in eastern and are summarised in Table 26.1.
26 Conservative Care for Patients with Chronic Kidney Disease 523
Table 26.1 Key elements of the Conservative Care pathway
Decision making Stability Increasing End of life care Care after loss
symptoms
Assessment Patient and family Patient and family Patient and family Family support
education education education
Education
Preservation of Preservation of Optimisation of Memorial events
Choice kidney function kidney function quality of life
Shared decision Optimisation of Optimisation of

making physical and physical and
cognitive function cognitive function
Symptom control Symptom control Symptom control
Creation of Increasing use of

community care network of
network community care
Introduction of Creation of advance Enactment of

advance care care plan advance care plan
planning
Crisis plan Crisis plan
Training and Empowering ssessment, Education, Choice

A
the Clinical Team and Shared Decision Making
Many patients and clinicians feel uncomfortable dis- Helping patients make meaningful choices requires
cussing later life care. Whilst the prognosis associ- cognitive, functional and physical assessment to
ated with ESKD) is often worse than that of some reveal multi-morbidity or functional decline previ-
cancers, many patients believe that kidney failure is ously unrecognised in short nephrology appoint-
curable with transplantation, and indefinitely treatments. Initial assessment is time-consuming but
able with dialysis. Few patients understand the true vital to true shared decision-making (SDM).
burden of dialysis, and some falsely believe that dial- Education necessitates practical information
ysis will help dementia or cure poor mobility. Studies about what treatment pathways entail and realis-
suggest that patients want to have their prognosis dis- tic prognostic guidance for patients and families
cussed but this is rarely done. Overly-optimistic esti- about survival and quality of life associated with
mates of prognosis on dialysis can accidentally lead each choice. Some patients may actively choose
to overemphasis on disease-directed care. to forgo dialysis whilst for others the decision
Staff sometimes have a poor understanding of may be consensus-driven, due to frailty or cogni-
limited prognostic information, little time or tive impairment.
knowledge to use systematised assessment tools, Table 26.2 shows possible assessment tools
and poor training in communication skills. Any which may help the clinician to guide realistic
CC programme is based on well-informed staff choices. Where resources allow, these tools
who are skilled and confident to deliver difficult should not be used to deny a patient their treat-
and complex information sensitively. Links to ment choice but to inform the SDM process.
staff training resources are included in the key Initial treatment discussions may focus on age and
tools table at the end of the chapter [4]. trajectory of GFR decline, to establish likelihood of
Table 26.2 Clinician Tools which help guide older frailer ESKD patients through treatment choices
524
Indicator Tools Relevance Evidence Limitation

Age Chronological age Easy to measure and understand Observational data suggest those > 70 with significant Only ever predicts
May improve discussions realism co-morbidity and those simply > 80 may gain little average survival in
survival advantage on RRT people of same age -
may not reflect the
individual
No RCT data yet
available (NIHR
PREPARE study
awaited)
Trajectory of Trajectory of GFR Shorter life associated with rapid Kidney Failure Risk Equation (KFRE)—internationally- Does not allow for
decline of kidney Proteinuria decline in kidney function may alter validated tool to calculate 2 and 5yr risk of ESRF acute events
function treatment choice. https://kidneyfailurerisk.com/ precipitating sudden
decline in renal
function.
Estimated survival US Renal Data system Use a mixture of demographic, Large national and regional renal databases from Europe Only exist for some
tools after RRT French REIN registry functional, biochemical and clinician and USA. populations
start (derived from New England HD clinics instinct in predictor scores to assess Need constant
large renal (sometimes called possible survival at 3 and 6 months updating
databases). Cohen tool) after dialysis initiation
https://qxmd.com/
calculate/
calculator_135/6-month-
mortality-on-hd#
H. Alston and K. Vinen
Physical frailty Clinical frailty Score Quick and easy for MDT to use Higher CFS (≥5) scores predict a greater likelihood of Not developed for use
(CFS) Co-morbidity based scale more hospitalization and death in patients <65 years
https://www.scfn.org.uk/ suitable for remote assessment Nursing home patients have only 13% chance of being More complex to
clinical-frailty-scale Higher Charlson scores are associated alive and at same level of function 1 year after RRT start calculate
Charlson score with increased 2 years mortality in
renal patients
Cognitive deficit MoCA Significant deficit may affect ability to Approximately 30-70% of haemodialysis patients have Requires literacy/
4AT contribute to treatment choice some degree of cognitive impairment. Incidence of vision to complete
Progressive deficit my impede ability cognitive impairment has been associated with both tests.
to receive treatment (unable to sit still) severity of chronic kidney disease and with rate of CKD Potential language
or to travel to unfamiliar dialysis unit decline and albuminuria. barrier for some
Visuospatial and executive functions disproportionately languages (though
affected in ESRF. NHANES III found slower learning some MoCA
speeds and impaired visual concentration even in translations exist).
younger CKD patients (aged 20-59), compared with
standardised populations. Implications for pre-dialysis
counselling, patient education and treatment compliance.
https://www.mocatest.org/
https://www.the4at.com/
Surprise question Would I be surprised if Uses synthesis of all knowledge about Nephrologists had a positive predictive power of 67%, Best used by
this patient died in the patient. with higher levels of accuracy when there was agreement experienced clinician
26 Conservative Care for Patients with Chronic Kidney Disease
next 6–12 months. between several clinicians who knows patient

well.
525
ESKD in the near future for older patients (some of Formal prediction tools may help patients to
whom have low but very slowly declining function). understand their comparative six-month survival
For those with a clear GFR decline, most patients chance were they to start dialysis. Co-morbidity
initially focus on length of survival. However, with should also be considered, as data suggest that for
limited data, discussions are often dominated by the those patients who enter CC, only about 50% die of
possibility (rather than probability) of life prolonga- uremia (with others dying from non-kidney related
tion (sometimes driven by the family not the patient). causes). Patients often perceive that death on the CC
Limited observational data has shown that for pathway will occur shortly after they would have
those over 70 with a WHO performance status of started dialysis. In fact, uremic death rarely occurs
≥3, those over 75 with ≥2 co-morbidities, or those until later, with a median survival of 6 months even
over 80 regardless of co-morbidity, there may be after GFR has fallen to 6–7 mL/min/1.73 m2.
little to no survival benefit in starting dialysis. Formal cognitive assessment aids clinical judge-
Higher clinical frailty scores predict an increased ment of a patient’s ability to understand complex
risk of hospitalisation and death in a renal popula- choices and management of practical aspects such as
tion, whilst starting dialysis from a nursing home possible disorientation in an unfamiliar dialysis unit.
is associated with only a 13% chance of one-year Factors that may help patients to consider
survival with a maintained level of functional sta- treatment options are shown in Fig. 26.1. In addi-
tus (with 87% of patients dying or declining). tion to overall survival, patients need support to
UNCERTAINTY
SYMPTOMS AND
FUNCTION:
Symptoms directly related
to kidney, Symptoms
related to wider needs,
Preservation of cognitive
and physical function
CULTURAL
SURVIVAL:
CONSIDERATIONS:
Overall survival and
Religious beliefs, nature of
treatment free survival
medical decision (individual
days
Patient or family
&
Family
QUALITY OF LIFE:
Desire to avoid PRACTICALITIES:
medicalisation and
Physical ability to attend
operations, hobbies, time
hospital, confusion in
with loved ones,
hospital, travel burden to
international travel,
dialysis
achieving PPC at end of
life
Fig. 26.1 Factors affecting patients’ treatment decisions

consider hospital-free days, symptom burden, Table 26.3 CKD treatment targets modified for CC
Population
freedom to travel, and the likelihood of achieving
a preferred place of death (which has been shown Measure Target Comments
to be more likely in those choosing CC). Blood ≤160/90 mmHg European Society
pressure of Hypertension
Limited studies have assessed quality of life on 2018 Guidelines
CC. One important longitudinal study compared >80 years
QOL in late CKD 4 and CKD 5 patients who had Many
hypertension
chosen a CC pathway, with those who had chosen
studies focus on
dialysis. Whilst the patients choosing CC were long term benefit
older, frailer and more co-morbid than those on rarely relevant in
dialysis, they maintained QOL, whereas for those CC
choosing dialysis, life satisfaction scores deterio- Diabetic HbA1c >7.5% Hypoglycaemia is
control greater risk in CC
rated after starting dialysis. All patients, especially
Cholesterol No target No evidence of
those with cognitive impairment, may find it hard relevance in frail
to understand the intrinsic uncertainty surrounding elderly.
treatments for the frail and elderly in ESKD. Any Acidosis Serum bicarbonate Evidence that
decision support tool must allow for this. >22 mmol/L acidosis may
contribute to
Data to support these difficult discussions are fatigue, muscle
largely based on small observational studies. The wasting and
British NIHR-supported PREPARE study is the malnutrition
first ever randomized control trial to look at out- Anemia 9.5–11.5 g/L If the patient is
asymptomatic,
comes in older frailer patients, comparing those lower levels of
who prepare to receive KRT with those who haemoglobin may
receive CC. Due to report in 2024, it will be a be acceptable
significant step forward in information available. High <6.5 mmol/L More relaxed
potassium targets may allow
improved
nutrition/QOL
easures to Prevent Progression
M Calcium and Immediate May help myalgia,
of CKD phosphate symptom benefit to pseudogout and
management keeping calcium restless legs
within normal Seeking to
Measures such as cessation of smoking, optimal range (eg normalize values
diabetic and blood pressure control and avoidance avoidance of to reduce vascular
of nephrotoxins are documented elsewhere in this fitting). calcification less
book. Factors that may receive attention in No specific target relevant for shorter
suggested for prognosis
younger patients (because they have long term phosphate—
sequelae) may be less relevant for those in later balance of QOL
life (e.g. high phosphate levels), or may need to and better nutrition
balance competing priorities e.g. high potassium with relevant
symptoms
(arrhythmia risk) versus quality of life (enjoyment Fluid and Sodium and total Where fluid
from eating). Risk factors may benefit from more sodium fluid intake may be overload not
pragmatic targets, e.g. the balance of tight blood restriction limited where significant, less
pressure or diabetic control against the risk of volume overload restriction may
and breathlessness improve nutrition.
falls due to postural symptoms or hypoglycaemia. are significant
There are no internationally agreed treatment tar- symptoms
gets for CC patients, but pragmatically the authors
use the suggested values shown in Table 26.3.
Excellent Symptom Control Formal assessment using tools such as the

Hospital Anxiety and Depression Scale (HADS)
Although patients in CC show considerable can help to reveal hidden depression which if
symptom burden (with on average 6–17 symp- left untreated is associated with higher morbid-
toms per patient), studies show that symptoms ity and mortality, higher functional dependence,
are often under-reported. Systematic use of and worse quality of life. Symptoms, together
assessment tools such as the POS-s renal are with possible therapies, are listed in Tables 26.4
recommended. and 26.5. As no international guideline exists,
Some symptoms clearly relate to deteriorating we have included pragmatic guidance as used
renal function (such as itching or nausea) and may by the authors.
come in clusters (such as pain relating to poor Studies have shown that with the input of a
sleep and depression relating to QOL), so improve- supportive care clinic, 57% of patients on CC can
ments in one may affect an entire cluster [5]. maintain similar or improved symptom scores
Depression is common amongst kidney and 58% have similar or improved QOL. Other
patients, occurring in 20–30% of patients. non-renal symptoms such as mobility or memory
Table 26.4 Common symptoms in CKD stage 5, and suggested therapeutic approach
% of CC Possible Non-
patients with contributing factor pharmacological
Symptom symptom for correction approach Pharmacological approach
Fatigue, Fatigue 70% Vit D deficiency Exercise Sleep disturbance
weakness, and sleep Metabolic acidosis Energy Gabapentin 50–300 mg at night*
sleep disturbance: Hypo or conservation Amitriptyline 5 mg at night gradually
disturbance 39% hyperthyroidism strategies increasing to a maximum of 25 mg
Anxiety and Optimise sleep Zopiclone 3.75–5 mg at night
depression. hygiene
Medication toxicity
e.g. Benzodiazepine,
anti-depressants,
opioids
Nociceptive 62% Investigate and treat Physiotherapy As per modified WHO analgesic ladder
pain underlying cause of Nerve blocks Step 1 Paracetamol to maximum dose of
pain Trigger point 1 g 4 times per day
injections Step 2 Tramadol to maximum 50 mg
twice daily (watch for toxicity of
accumulation)
Step 3 Transdermal buprenorphine
starting at 5 ucg per hour release
Neuropathic 62% Investigate and treat Physiotherapy Gabapentin 50–300 mg per 24 h*
pain underlying cause of Nerve blocks Amitriptyline 10–25 mg per day
pain Trigger point Tramadol 25–50 mg (max 100 mg per
injections 24 h)
Buprenorphine transdermal patch
increasing gradually from 5 mcg per
hour
Uraemic 55% Anemia and iron Emollients with Gabapentin 50–300 mg daily 1–2 h
pruritis deficiency high water content before sleep*.
Allergies, Camphor 0.25%/ Tricyclic anti-depressants e.g.
infestation, contact menthol 0.25% amitriptyline 10–25 mg before bed
dermatitis emollient Anti-histamines—although little
Dry skin Avoid skin evidence well tolerated and easy to judge
Heat warming such as if effective e.g. cetirizine
hot baths and
electric blankets
Short nails
Night-time gloves

% of CC Possible Non-
contributing factor
patients with pharmacological
Symptom symptom for correction approach Pharmacological approach
Anorexia 49% Over -restrictive Loosen diet No convincing pharmacological
renal diet advice See below interventions
Chronic nausea Drug review
Poor gastric See below
emptying due to
drug toxicity eg
opiods
Depression/social
isolation/fatigue
Breathlessness 39% Anxiety Sit up Frusemide 40–500 mg per 24 h.
Correct Anaemia Humid Erythropoietin
Correct Acidosis environment Sodium bicarbonate (balance correction
Treat Pulmonary Salt and fluid of acidosis against sodium load)
oedema advice
Treat Infection
Anxiety and Anxiety 34% Sleep disturbance Psychological Sertraline 50 mg od
depression Depression Untreated pain support Amitriptyline 10–25 mg at night
28% Citalopram 10 mg at night
Restless-leg 28% Anemia and iron r/o alcohol, Gabapentin 50–300 mg daily 1–2 h
syndrome deficiency caffeine, before sleep*
stimulants Pramipexole and rotigotine dermal patch
(require very slow titration)
Clonazepam 500 mcg nocte if RLS
associated with sleep disturbance
Nausea and 27% Metabolic Treat constipation Ondansetron 4–8 mg per 8 h PRN
vomiting disturbance Small frequent Metoclopramide 10 mg up to three times
GI disturbance eg meals per day before meals.
delayed gastric Haloperidol 0.5 mg every 8 h
emptying (can be increased to max 5 mg per 24 h
Review medications in severe refractory cases)
(opioids and
anti-depressants)
Increase dose gradually, with long interval to minimize toxicity due to accumulation
*
Table 26.5 End of life symptom management in CKD stage 5

Mild pain, or fevers Paracetamol/acetaminophen, 650–1000 mg QDS (max 4 g/24 h)
Pain Opioids: fentanyl and oxycodone generally better tolerated, with
Pain is not a common feature of ESKD, but fewer side effects, than morphine and codeine
may be caused by other comorbidities. Starting doses:
The starting doses shown are for opioid-naïve Oxycodone po/sc 2.5–5 mg 2–4 hourly, titrate up as required
patients—if a patient is already taking opioid or
painkillers, the dose should be converted to Fentanyl sc 25 mcg 2–4 hourly prn, titrated as required
take account of this (see BNF, or local
palliative care conversion tables)
Nausea Cyclizine 50 mg tds (max 150 mg/24 h)
or
Ondansetron 4–8 mg 2–3 times daily
or
Metaclopramide 10 mg tds
or
Haloperidol 0.5–1 mg bd
or (intractable nausea)
Levomepromazine 6mg nocte orally, or 2.5–5 mg by subcutaneous
injection
(continued)

Mild pain, or fevers Paracetamol/acetaminophen, 650–1000 mg QDS (max 4 g/24 h)
Shortness of breath Furosemide—very high doses (250–500 mg per day) may be
required in end stage renal disease
Fluid restriction <750 mLs/day (and salt restriction to manage
thirst)
Opioids, such as fentanyl or oxycodone
Secretions Glycopyrronium 400–600 mcg (max 2.4 mg in 24 h)
or
Hyoscine hydrobromide 400 mcg qds
Agitation Midazolam 0.5–1.0 mg every 4–6 h
or
Haloperidol 0.5–1.0 mg bd
Itch, dry skin Emollients and other measures such as soap substitutes and
This is a common symptom, often at higher avoiding triggers such as hot baths, or dry air (use a humidifier)
eGFRs (<15 mL/min). Antihistamines
Often blamed on high serum phosphate levels, Menthol 0.25%/camphor 0.25% in emollient cream
there is no evidence that use of phosphate Capsaicin 0.025% cream
binders reduces uraemic itch, and tight dietary Gabapentin 100 mg nocte, or pregabalin 25 mg nocte
restrictions may not be appropriate at end of life. Consider referral to dermatology for UVB phototherapy
Lifestyle modification to avoid triggers, and use
of emollients/topical creams is often sufficient
to manage symptoms.
difficulties, however, may relate to the wider The CGA assessment process has been shown
health needs of the aging, frail patient; these are to improve outcomes in older clinically frail
addressed in a later section. patients when assessed during hospital admissions,
as measured by an improved chance of living in
their own home one year after hospitalisation. It
Drug Chart Review identifies medical, social and functional needs and
uses an MDT approach to create a coordinated
Many CC patients have acquired long burden- care plan. Key domains of assessment may include
some drug lists. Some have little prognostic value depression/anxiety, falls risk, cognition, polyphar-
for later life, others have significant side effects macy, continence, skin integrity, nutrition, ADLs
(e.g. anti-cholinergic drugs). Some are no longer and social issues, with relevant referrals and sign-
indicated but have remained on charts, whilst posting to services such as memory and falls
others previously carried a clear indication but clinic, or occupational and physiotherapy service.
have been ineffective. Such wider needs e nquiries may also help patients
Regular reviews using tools such as STOPP- and families to understand that correcting renal
START can minimise both tablet burden and side function alone is unlikely to improve quality of
effects. life, and time may be better spent on other inter-
ventions including advance care planning (ACP).
Wider Needs Assessments

Creating a Network of Care
When kidney disease is advanced and drug man-
agement more specialised, a kidney clinic is often Nephrology services can offer excellent symp-
the principal source of support for CC patients. tom management and psychological support for
However, many suffer with geriatric syndromes, patients and their families, but true 24 h holistic
so ideally teams should build networks of care end of life care requires involvement of the
including access to comprehensive geriatric wider multidisciplinary community team,
assessment (CGA) [6]. including inter-agency working (Fig. 26.2).
Family
Social Supportive
workers care nurses
Health aides /
carer Nephrologist
assistants
Patient
Physiotherapy
Palliative care
/ Occupational
team
therapy
Primary care
Priest / Imam / physician / GP
Pastor / Family
doctor
Heart Failure
team /
District
Geriatricians /
Nurses
Other medical
teams
Fig. 26.2 Elements of a Network of Care
Palliative Care Teams

An existing network of care will ease the tran-
sition from secondary care to community end of
The palliative care team may provide community
life care, and reduce the chances of poor com-
symptom management, help with creating
munication. Local health service arrangements
Advance Care Planning documents (ACP), and
will dictate precisely which other agencies need
support for families.
to be involved, but consider creating links with
the following teams:
rimary Care/General Practitioners/

P ers and next-of-kin, are involved in these discus-
Family Medicine sions and are aware of the contents of an ACP.
Topics that may be covered include:
Involvement of the primary care team is vital,
both for community prescribing, and for a holis- –– preferred place of death,
tic overview of the patient’s other medical prob- –– spiritual beliefs
lems. They may carry out home visits, and be –– treatments that they would and would not
involved in the drawing up of community DNAR wish to undergo (including resuscitation),
(Do Not Attempt Resuscitation) orders and –– next-of-kin
ACPs. –– a list of relevant legal documents such as
Advance Directives, or medical Lasting
Powers of Attorney, so that the medical team
Social Work are aware they exist.
Social workers, from nephrology or palliative A recent meta-analysis found that creation of an
care, can provide advice on accessing benefits ACP was associated with greater achievement of
entitlements, arranging homecare, and obtaining preferred place of care at death (PPC), and
equipment such as commodes and hospital beds. increased hospital-free days in the last year of life.
The proportion of patients completing an ACP is
widely seen as a surrogate marker for good pallia-
istrict Nursing/Community Nursing
D tive care provision, and is used as a performance
Teams indicator (the only performance outcome measure
for renal palliative care services agreed by both
These teams may administer Erythropoetin, admin- patients and staff in a recent Delphi exercise).
ister end of life medications, provide wound care,
and provide pressure area monitoring.
Family Support After Bereavement
Social Care/Home Health Aides Patients and families often know the nephrology
team well, after years of renal care. Seamless
These provide personal care to patients, allowing transition is important so that patients and their
them to stay in their own homes, while relieving families do not feel “abandoned” by the move to
some of the burden on family members. Good community end of life care.
home care is essential to prevent unnecessary As well as formal grief counselling and sup-
hospital admissions. port, which may be available via the primary
care and/or community palliative care teams,
some centres send a condolence card, or organ-
Advance Care Planning ise an annual departmental Service of
Remembrance for patients who have died in the
Creating an Advance Care Plan allows patients to last twelve months (often appreciated by
express their wishes about the end of life. nephrology staff).
In many countries, ACPs are not legally bind- This is also important from the perspective of
ing, but are a useful way to structure a patient’s other patients within the department. If they feel
thoughts and discussions about priorities, and how that deceased patients are “brushed away” and
they envisage the end of their life. It is important forgotten, they may worry that the same will hap-
that families, particularly surrogate decision-mak- pen to them when they die.
Conclusions ficulties which might impact on her ability to

travel to a dialysis facility. Patient are not
For the 85 year old gentleman referred for con- always aware of or willing to disclose mem-
sideration of kidney replacement therapy, his sur- ory difficulties; the fact that she no longer
vival advantage with dialysis is very limited [e.g does her banking may hint at some loss of
using Cohen’s tool, his chance of surviving the cognitive function which may impact on her
first six months on dialysis is just 50%]. A better ability to understand complex treatment
option for his further management may be for choices. Her own priorities are vital as recog-
personalised conservative care to delay progres- nition that regular trips to see a beloved sister
sion of his CKD, symptom control and advanced in India several times a year are a top priority
care planning. may make a relatively constraining treatment
Despite huge advances in renal care, evidence such as dialysis less attractive. Her rate of
suggests that not all kidney patients genuinely GFR decline will directly impact her esti-
benefit from kidney replacement therapy. The mated survival if she chooses conservative
alternative conservative care pathway offers a kidney management so is a vital part of early
high-quality holistic pathway for those in whom assessment.
there will be no benefit, or for those who choose 2. She chooses conservative care. You meet her
not to undergo the complexities of kidney later when she has developed more symptoms
replacement therapy in their frailer years. particularly neuropathic pain, poor sleep and
Focusing on symptom control and addressing low mood. How do you approach this
their wider needs (often related to co-morbidity), problem.
as well as building an excellent network of care A. Tell her this is not related to her kidneys,
and planning for the last days of life are all vital and she should see her GP
elements. It is always the duty of a professional B. Explain it is a normal part of ageing, and
to enable a patient to live well, but it is equally she shouldn’t expect to feel as healthy as
important to ensure patients approaching end of she did when she was a girl.
life are also able to die well (Table 26.6). C. Carry out a comprehensive assessment of
her symptoms, and institute a manage-
ment plan which may involve both phar-
Questions macological and non-pharmacological
interventions.
1. An 81 year old comes to AKCC with her D. Start gabapentin 300 mg nocte for her
grandson. She has an eGFR of 12 mL/ neuropathic pain, diazepam 10 mg nocte
min/1.73 m2 and is of Indian heritage. She for her poor sleep, and mirtazapine 15 mg
manages well, living with a supportive family nocte for her low mood.
and has no professional carers. She has not E. Start a buprenorphine patch for her pain
noticed any memory difficulties but no longer C. The causes of her pain, poor sleep and low
does her own banking. Which aspects of mood may be multifactorial, and may also be
assessment may help you guide her through inter-related. For example, if she is anxious
her treatment choices ? about her renal prognosis, this may be caus-
A. Clinical frailty score alone ing her low mood and poor sleep, and this
B. MoCA alone may increase the intrusiveness of her pain.
C. Assessment of patient’s current priorities Careful and thorough history-taking is impor-
D. Consideration of rate of GFR decline tant to unpick the many aspects of her
E. All of the above symptoms.
E. Despite the patient managing well without Renal patients experience high levels of
professional carers, a high level of family sup- medication side-effects, due to both poly-
port may mask mobility or other practical dif- pharmacy, and accumulation of renally-
534
Table 26.6 Tools available to support conservative care (CC) programmes

Tool /programme Focus Link
Staff training
Vital talk Teaching resource for staff communication training https://www.vitaltalk.org/
CKM Care Resources of conservative kidney management HYPERLINK "http://www.ckmcare.com
programme developed by Alberta Health Service, " www.ckmcare.com
Canada.
Kidney Supportive Care: CPD covering all aspect of Conservative Care See Gelfand et al. [4]
Core Curriculum 2020
ACP toolkit NHS/British Geriatric Society resources to help staff https://ihub.scot/project-toolkits/anticipatory-care-planning-toolkit/anticipatory-
start the ACP process care-planning-toolkit/guidance-for-health-and-social-care-professionals/
https://www.bgs.org.uk/sites/default/files/content/attachment/2018-04-18/
Advance%20Care%20Planning%20Guideline.pdf
https://www.goldstandardsframework.org.uk/advance-care-planning
Patient assessment tools
Clinical Frailty Score Simple visual scale that can be used by all members of https://www.nice.org.uk/guidance/ng159/resources/
MDT to assess level of frailty clinical-frailty-scale-pdf-8712262765
Charlson Comorbidity Index Scoring system for comorbidity, higher scores https://www.mdcalc.com/charlson-comorbidity-index-cci
associated with worse mortality
Edmonton Frail Scale Detailed assessment of frailty—includes physical and https://www.cgakit.com/fr-1-edmonton-frail-scale
cognitive assessment
WHO performance Scored from 0 (asymptomatic) to 5 (dead) https://www.nice.org.uk/guidance/ta121/chapter/
status appendix-c-who-performance-status-classification
Karnofsky Performance Scored from 100 (well) to 0 (dead) https://www.mdcalc.com/karnofsky-performance-status-scale
Scale (KPS)
BGS Clinical Frailty toolkit Toolkit containing practical resources for assessing https://www.england.nhs.uk/rightcare/wp-content/uploads/sites/40/2019/07/
frailer patients frailty-toolkit-june-2019-v1.pdf
Decision support tools
Alberta Health Services Tool to help patients decide whether CC or RRT is right www.ckmcare.com
for them
YoDDA (Yorkshire Dialysis Accurate and balanced information about RRT/non-RRT http://www.yodda.leeds.ac.uk/Survey/Information
Decision Aid) options
Symptom assessment tools
POS-S Renal Palliative care symptom assessment tool adapted to https://www.ncbi.nlm.nih.gov/portal/utils/pageresolver.fcgi?recordid=5ff1be23bdb3
include common symptoms of CKD 052f32e0c7cf
Treatment guidance tools
STOPP START tool Toolkit to help clinicians reduce polypharmacy https://www.cgakit.com/m-2-stopp-start
H. Alston and K. Vinen
excreted metabolites. Many prefer to “put up decision before making any hard-to-
with” symptoms in order to reduce pill bur- reverse changes to her management plan.
den. Non-pharmacological treatments such as E. It is important to establish why she has
sleep hygiene, gentle exercise and counsel- changed her mind—have her symptoms wors-
ling for low mood and lethargy, distraction ened, or do her family believe that she will
techniques and medicated emollients for pru- live longer if she chooses to have dialysis?
ritis and neuropathic pain, and simply She has attended with her grandson in the
addressing her health-related concerns past, but he may not be the family’s main
directly in a gentle and reassuring way, may decision-maker. Ensure her whole family
reduce many of her symptoms to a more man- have a clear understanding of what dialysis
ageable intensity. can and cannot achieve, and understand that
GPs often shy away from prescribing in her life expectancy is limited either with or
CKD stage 5, and it is the responsibility of the without dialysis.
nephrology team to provide guidance on med- Manage any new symptoms, and reassure
ications which are and are not safe to use in her that she will not be in any pain or discom-
these patients, with appropriate dose reduc- fort (fluid overload is particularly difficult for
tions where necessary. patients to tolerate, and is a frequent trigger
It is true that “she should not expect to feel for decisions to change modality, but can
as healthy as she did when she was a girl”, but often be managed well without dialysis).
it is also unhelpful and does nothing to address Alternatively, she may have chosen CC in
her very treatable symptoms. Neither does it the past, to avoid dialysis “unless I really need
foster a good doctor-patient relationship. it”—many patients, particularly those who are
Gabapentin certainly has an important older, are extremely keen to avoid upheaval
place in the management of neuropathic pain, and change in their lives, and may choose to
but 300 mg nocte is too high a starting dose delay dialysis discussions for the time being
and is likely to lead to over-sedation, which by choosing conservative management.
will also increase her falls risk. Prescribing Others, with executive function impairment,
gabapentin in combination with diazepam and may have been unable to make a decision
mirtazapine, in a naïve patient with CKD about modality until a crisis point has been
stage 5, would be extremely dangerous. reached. Families will often report “she didn’t
Buprenorphine is not indicated for first- really understand what she was agreeing to”.
line management of neuropathic pain. A trial of dialysis may seem a good option but
3. Her symptoms improve but 12 months later can often extend for several months. Such lon-
with an eGFR of 7 mL/min/1.73 m2, her fam- ger trials can lead to loss of native function so
ily ask for her to be seen urgently as she has that if she subsequently decides to stop, she
“changed her mind and wishes to have dialy- may have a shorter life expectancy than if she
sis”. How do you approach this request? had not commenced dialysis.
A. Arrange an urgent dialysis start 4. Three months later, she and her family are
B. Suggest a trial of dialysis happy with Conservative Care, but she and
C. Decline the request as she has previously her family still want her to be resuscitated.
made a choice for to follow a conservative How do you approach this?
management pathway A. Accept that it is her right to request CPR,
D. Meet the patient with her family, confirm even if it would be futile.
that she does wish to change her treatment B. Seek advice from the hospital legal team
pathway and organise line insertion to about lack of concordance of views in
start dialysis. CPR status
E. Meet the patient with her family, and find C. Agree to CPR for her and her family’s
out what has prompted this change of peace of mind.
D. Explain that CPR is a medical decision, of life. She has now developed symptoms
and complete a DNAR order for her. (agitation and restlessness), which are not
E. Talk to her about her understanding of CPR, controlled by her current medications, and
and her ideas about end of life in general. which are causing her and her family some
E. Many people, particularly older patients, worry distress.
that agreeing not to be resuscitated means that Ideally, the community palliative care team
they will not receive any medical care at all. (or local equivalent) would already be
Reassure her that this is not the case. Explain involved in her care. If not (perhaps because
what is involved in resuscitation, and what CPR this deterioration was unanticipated), an
can and cannot do. Explore her plans for end of urgent referral should be done.
life (preferred place of death, degree of medi- An emergency home visit needs to be
calisation, etc), and whether CPR would align made, this evening, by either the renal
with those goals. Help her to complete an ACP team, palliative care team, or family doctor
document which sets out her wishes. Whilst it is (the most appropriate person will depend
important to be up to date with the legal posi- on the structure of local services), and a
tion in your own health care system, these full assessment of her symptoms and care
situations generally reflect communication dif- needs should be made. It is not reasonable
ficulties, which should be addressed first. to leave her in distress until the following
5. She confirms that she does not want to be day.
resuscitated, and wishes to die at home with It is also not reasonable ask a family to
her family. Six months later, you are called by bring a dying woman to the ED, as there is a
her daughter. She has been in bed for the past high chance of her either dying during the
two weeks, and has been sleeping for most of journey, or in a distressing environment such
the day. Tonight, she has woken and is very as the busy ED treatment area, instead of at
restless and agitated. Her daughter is distressed, home as she wished.
and asks for help. What do you suggest? For symptoms such as terminal agitation, a
A. Bring her in to the Emergency Department combination of either midazolam or haloperi-
for an assessment. dol, plus fentanyl, may be added to a syringe
B. Tell her daughter it sounds like she needs driver to manage her symptoms overnight. A
to start dialysis full assessment of her care needs (physical,
C. She has chosen supportive care, so is no emotional, spiritual, and family support
longer a renal patient—they should call needs) can be made once the immediate crisis
her GP in the morning has passed.
D. This sounds like terminal agitation, and
they need urgent palliative care input to Test your learning and check your under-
manage her symptoms standing of this book’s contents: use the
E. Explain that you will write a referral to the “Springer Nature Flashcards” app to access
local hospice team. questions using https://sn.pub/cz9Cok. To use
D. The history of increasing sleepiness and leth- the app, please follow the instructions in Chap.
argy suggest that this lady is approaching end 1.
References part of kidney services across a range of income

settings around the world. Kidney Int Suppl.
2020;10(1):e86–94.
1. Davison SN, Levin A, Moss AH, et al. Executive sum- 4. Gelfand SL, Scherer JS, Koncicki HM. Kidney sup-
mary of the KDIGO Controversies Conference on portive care: core curriculum 2020. Am J Kidney Dis.
Supportive Care in Chronic Kidney Disease: develop- 2020;75(5):793–806.
ing a roadmap to improving quality care. Kidney Int. 5. Raghavan D, Holley JL. Conservative care of the
2015;88(3):447–59. elderly CKD patient: a practical guide. Adv Chronic
2. Brown EA, Brown E, Chambers EJ, Eggeling C. End Kidney Dis. 2016;23(1):51–6.
of life care in nephrology: from advanced disease to 6. Nixon AC, Brown J, Brotherton A, et al.
bereavement. OUP Oxford; 2007. Implementation of a frailty screening programme and
3. Hole B, Hemmelgarn B, Brown E, et al. Supportive Geriatric Assessment Service in a nephrology centre: a
care for end-stage kidney disease: an integral quality improvement project. J Nephrol. 2020;
Electrolytes & Acid Base Disorders
27
Gates B. Colbert, Ajay Kher, Kareem Genena,
and Edgar V. Lerma

A 48-year-old man with a past medical history of
Heart Failure with Reduced Ejection Fraction Volume management is a difficult clinical prob-
(HFrEF) 25% and Chronic Kidney Disease Stage lem for patients with HFrEF and CKD. Patients
III (CKD) is referred to the emergency room frequently retain sodium and water, due to
from CKD Clinic. He has been struggling with decreased kidney perfusion and increase renin-
volume overload and his diuretic Torsemide has angiotensin activation from both disease states.
been increased from 20 mg per day to 100 mg per Electrolyte balance can be difficult with both
day. He reports weight loss of about 10 kg and Hyper- and Hypo- electrolyte conditions due to
improvement in his edema. The patient has been diet, medications, and treatments of HFrEF and
urinating large volumes for several weeks and CKD. This chapter will address the electrolyte
reports increased fatigue. His vital signs were imbalances above, as well as the opposing high
within normal ranges, but outpatient labs returned or low electrolyte clinical scenarios.
abnormal with Na 121 mEq/L, K 2.9 mEq/L, Cl
95 mEq/L, HCO3 38 mEq/L, BUN 44 mEq/L,
and Cr 1.5 mg/dL. Hyponatremia
Hyponatremia is defined as a serum sodium con-

centration, Na <135 mEq/L, and is encountered
in up to 30% of hospitalized patients (Table 27.1)
[1, 2]. A few key concepts should be reviewed to
G. B. Colbert facilitate the management of this disorder
Texas A&M College of Medicine at Dallas,
Dallas, TX, USA (Table 27.2).
e-mail: Gates.Colbert@BSWHealth.org
A. Kher 1. Serum Na is determined by the sum of total
Vishwasth Clinic, Noida, Uttar Pradesh, India body exchangeable sodium and potassium
e-mail: ajay@vishwasth.com divided by total body water [3]. In fact, most
K. Genena disorders of Na are secondary to changes in
Baylor University Medical Center, Dallas, TX, USA total body water rather than changes in total
E. V. Lerma (*) body sodium.
Section of Nephrology, University of Illinois at 2. Serum Na is the major determinant of serum
Chicago College of Medicine/Advocate Christ osmolality and is tightly regulated by an inter-
Medical Center, Oak Lawn, IL, USA
https://doi.org/10.1007/978-3-031-09131-5_27
540 G. B. Colbert.
Table 27.1 Causes of hypotonic hyponatremia
Category Examples Notes

Impaired kidney function Acute kidney injury Look for urine output and GFR
Chronic kidney disease
Thiazide diuretics Impaired urine dilution
Overwhelmed diluting Tea and toast syndrome uOsm < 100 mosm/kg
capacity Beer potomania
Psychogenic polydipsia
Unsuppressed ADH, Cancer: lung, blood,
“inappropriately” lymphoma, gastrointestinal
Lung: infection, respiratory
failure
CNS: bleeding, infection
Medications: NSAIDs, SSRIs,
cyclophosphamide
Nausea, pain Nausea is a potent stimulus of
ADH
HIV
Hypothyroidism Only in severe cases
Adrenal insufficiency Cortisol normally suppresses
ADH
Nephrogenic SIAD Increased action of ADH
Others Reset osmostat
Cerebral salt wasting CNS pathology, labs like SIAD
but hypovolemic
NSAID: non-steroidal anitinflamatory drugs, SSRI: selective serotonin reuptake inhibitors, HIV: human immunodefi-
ciency virus, CNS: central nervous system
Table 27.2 Diagnostic Approach to Hypotonic Hyponatremia
Hypovolemia Euvolemia Hypervolemia
U osm > 100 Mineralocorticoid SIAD Heart Failure on U Na > 30

deficiency diuretics
Cirrhosis on
diuretics
Renal Failure
Volume depletion, Heart Failure U Na < 10

extrarenal losses Cirrhosis
U osm < 100 Overwhelmed

diluting capacity
27 Electrolytes & Acid Base Disorders 541
play between the pituitary gland and the kid- occurs within 48 hours. When the exact onset is
ney, primarily by adjusting the stimulation for unknown, the case in most patients, hyponatre-
free water intake and excretion. Changes in mia is treated as chronic. Rapid correction of
blood volume regulate antidiuretic hormone hyponatremia causes osmotic shifts across the
(ADH) secretion from the posterior pituitary blood brain barrier and can lead to the devastat-
as well. ing ODS (paraplegia, dysarthria, and dysphagia).
3. Urine is theoretically divided into two vol- Risk factors for ODS include severe hyponatre-
umes: solute clearance (urea and electrolytes) mia (<120 mEq/L), hypokalemia, malnutrition,
and free water clearance. Solute clearance is alcoholism and liver disease.
the volume of urine needed to excrete the Sodium > 130 mEq/L is usually managed in
ingested solute load. In the face of hypoosmo- the outpatient setting. Chronic asymptomatic
lality, the normal renal response is to increase moderate hyponatremia (Na 120–130 mEq/L)
electrolyte-free water excretion. In the can be treated in the outpatient setting as well.
pathologic syndrome of inappropriate antidi- For acute symptomatic hyponatremia, such as a
uresis (SIAD), the kidneys produce concen- patient presenting with seizures and a Na of
trated urine in the face of a hypo-osmolal 110 mEq/L or less, raising the serum Na concen-
serum. A simplified way to look at electrolyte tration by 4–6 mEq/L in the first hours is usually
free water clearance is through the equation: sufficient to abate the symptoms. A limit correc-
urine [Na] + urine [K]/serum [Na] [4]. A ratio tion of 10–12 mEq/L per day for patients at regu-
nearing or exceeding 1 indicates low electro- lar risk for ODS, and 8 mmol/L per day for
lyte free water excretion. A ratio much below patients at higher risk of ODS is suggested by US
1 indicates the opposite. guidelines. However, correction should not
4. Serum [Na] is measured in the whole serum exceed 18 mEq/l per day in any 48-hour period.
(water and solid phases). Only the sodium European guidelines recommend a limit of
concentration in the water phase is physiolog- 10 mEq/L in the first 24 h and 8 mEq/L in the
ically important. Conditions which increase following days. The higher the risk of ODS, the
the solid phase such as hyperlipidemia or slower the correction should be. For a malnour-
paraproteinemia cause the serum [Na] mea- ished cirrhotic presenting with a Na of 105 mEq/L
sured by most blood chemistry analyzers to be and a potassium of 2 mEq/L, a Na rise of 6 mEq/L
low. Measured blood osmolality makes the in the first day is a reasonable goal.
distinction between true hypotonic hyponatre- A 3% saline infusion is used to achieve a
mia and pseudo- or isotonic hyponatremia. prompt rise in serum sodium concentration.
Blood gas and point-of-care chemistry ana- Intermittent boluses of 100–150 mL over
lyzers provide accurate [Na] in these 10–20 min, or slow continuous infusions can be
circumstances. used. The expected correction of [Na] with each
liter of infused fluid can be calculated using the
Androgue-Madias equation: ([Na]
Treatment of hyponatraemia infusate − [Na] serum)/(total body water + 1).
This equation does not consider oral fluid intake,
Rate of sodium correction depends on severity, urine production nor other infused intravenous
acuity, symptoms, and risk fluids. Repeated measurement of Na is therefore
of osmotic demyelination syndrome (ODS). necessary when managing hyponatremia.
Symptoms of severe hyponatremia include nau- Attention to urine output is important. A brisk
sea, vomiting, headache, altered mental status, diuresis could mean excretion of large amounts
and seizures. Patients with underlying intracranial of dilute urine and rapid correction. Urine chem-
pathology are at a higher risk of developing istries can be repeated along the course of treat-
severe symptoms of hyponatremia such as coma ment. Overcorrection can be treated with
from brain herniation. Acute hyponatremia hypotonic fluids +/− desmopressin. Concomitant
542 G. B. Colbert.
use of desmopressin with 3% saline is advocated restricted. Rarely, a hypothalamic disorder impair-
for by some and has been shown to reduce the ing thirst is the culprit in hypernatremia. The pre-
incidence of overcorrection. dominant symptom of hyponatremia is thirst.
Altered mental status has been associated in severe
cases.
Hypernatremia
Etiology Diagnosis
Hypernatremia is defined as a serum Two primary diagnostic questions can help solve
Na > 145 mEq/L, and could be secondary to water a case of hypernatremia:
deficit (most common), solute excess, or water
shift into cells (Tables 27.3 and 27.4). 1. Is there a loss of water?
Hypernatremia results in hypertonicity and nor- 2. Why is the patient not drinking appropriately?
mally stimulates the thirst mechanism with ADH
release and subsequent production of a concen- Non-kidney water loss is evident from the
trated urine. Restricted or insufficient water intake patient’s history. Kidney water loss is manifested
is necessary for hyponatremia to develop. Even as polyuria and is divided into 2 main categories:
individuals with complete diabetes insipidus (DI) diabetes insipidus and osmotic diuresis. The kid-
maintain near-normal [Na] if access to water is not ney’s ability to concentrate urine in cases of non-
Table 27.3 Causes of Hypernatraemia
A. Water Deficit Non-Kidney water loss Vomiting
Diarrhea
Sweat
Insensible losses
Kidney water loss Central diabetes insipidus
Nephrogenic diabetes insipidus
Osmotic diuresis
Adipsia
B. Solute Excess Ingestion of salt
Infusion of hypertonic solution
Mineralocorticoid excess
C. Shift of Water into Cells Seizures
Excessive exercise
Table 27.4 Causes of Kidney water loss
Central Diabetes Insipidus Mutations in vasopressin
Pituitary tumors and infiltrative disease
CNS infections
Neurosurgery and trauma
Anoxic encephalopathy
Idiopathic
Nephrogenic Diabetes Insipidus Mutations in V2 receptor or aquaporin 2
Drugs (e.g., lithium, amphotericin B,

demeclocycline)
Kidney interstitial disease
Obstructive uropathy
Hypokalemia
Hypercalcemia
Osmotic Diuresis Glucose
Urea
Mannitol
kidney water loss is usually preserved and the x urine volume) typically exceeds 1000 mosm/
urine osmolality is typically >600–800 mosm/kg. day. In states of solute excess, the extracellular
The urine osmolality in central and complete space is usually expanded and urine Na is typi-
nephrogenic DI is usually <300 mosm/kg but cally >100 mmol/L (Fig. 27.1).
could be higher in partial nephrogenic Limited access to water is often due to altered
DI. Response of the urine osmolarity and volume mental status or physical debility. A hypothalamic
to exogenous desmopressin differentiates central lesion impairing the thirst mechanism should be
from nephrogenic DI. In cases of osmotic diure- suspected in alert patients with free access to
sis, the daily osmole excretion (urine osmolality water.
544 G. B. Colbert.
Posm > 295 mosm/kg
Na > 145 at baseline Water Restriction Test
Uosm
> 500 < 500

NOT renal wate loss Diabetes Insipidus
DDAVP
Uosm Inc > 50% Uosm Inc > 50%

Central DI Nephrogenic DI
Fig. 27.1 Algorithm for determining central vs nephrogenic diabetes insipidus
Treatment of Hypernatraemia water loss since the urine osmolality is fixed at a

low value. Thiazide diuretics impair the distal
The water deficit can be estimated from the equa- tubule’s diluting capacity. Amiloride can be used
tion: {(serum [Na] − 140)/140} × total body in lithium-induced DI.
water. The rate of correction should be limited to Adipsia: Forced water intake with monitoring
12 mEq/L per day. One liter of dextrose 5% water of weight, urine output and point of care [Na]
provides 1 L of free water, while 1 L of 0.45% when available.
saline provides 500 mL of free water. Concomitant Solute excess: Loop diuretics together with
volume depletion should be treated with isotonic free water.
fluids before the water deficit is replaced with
hypotonic fluids.
Non-kidney water loss: The source of water Hypokalemia
loss should be addressed if possible.
Osmotic diuresis: Hyperglycemia should be The majority of potassium is intracellular and
treated. High protein feeding should be modified. initial buffering (intracellular shifts) of potas-
Central DI: Treated with desmopressin ace- sium absorbed from diet is critical to ensure that
tate. Usual maintenance dose is 10–20 mcg intra- extracellular potassium does not have large shifts
nasally once or twice daily. post meals (Fig. 27.2). Any alterations in these
Nephrogenic DI: Electrolytes abnormalities mechanisms can lead to hypokalemia or hyperka-
should be corrected, and offending medications lemia (Table 27.5).
should be discontinued if possible. A low-salt Kidney elimination of potassium is critical for
and low-protein diet reduces the obligate kidney maintaining potassium homeostasis. Kidney
Acid Base Urinary K Excretion
Metabolicacidosis Metabolicacidosis Metabolicalkalosis Metabolicalkalosis

with Low Urinary K with high Urinary K with low Urinary K with high Urinary K
Lower GI losses
(eg: diarrhea, Renal Loss (DKA, Surreptutious
Laxative abuse, Type 1 or Type 2 Vomiting or diuretic Renal Loss
villous adenoma) RTA) with effect worn off
Normal or low BP High BP

Gitelman, Bartter, Mineralocorticoid,
Diuretic (urine CI) diuretic in HTN
Fig. 27.2 Diagnostic algorithm for hypokalemia
elimination is determined by the following fac- Signs and symptoms of hypokalemia are listed
tors: adequate distal tubular delivery, serum in Table 27.6. The three most common causes of
potassium, and the presence of aldosterone. Due hypokalemia are vomiting, diarrhea, and diuret-
to the huge adaptability of the kidney excretion ics and these are usually self evident on history
of potassium (20 meq–400 meq), diet alone is and examination (Table 27.5). However, if etiol-
seldom a cause for hypokalemia or hyperkale- ogy is not clear a systematic evaluation requires a
mia, though it can be a contributing factor. combination of acid- base status (metabolic aci-
Changes in distal delivery, Aldosterone, or kid- dosis/metabolic alkalosis) with kidney potassium
ney function can lead to hypokalemia or excretion (low or high potassium excretion) to
hyperkalemia. provide the answer (Fig. 27.2).
546 G. B. Colbert.
Table 27.5 Causes of Hypokalemia
Low potassium dietary intake (not usually sole cause)

Transcellular shift of potassium Increased pH (metabolic alkalosis)
Increased insulin
Increased Beta adrenergic activity
(stress or medications)
Periodic paralysis
Cell Turnover (treatment of
megaloblastic anemia/ GM-CSF)
Pseudohypokalemia (eg: AML, post blood
collection)
Others Barium intoxication
Chloroquine intoxication
Renal Loss of potassium Loop and thiazide diuretics
Gitelman and Bartter Syndrome
Increased mineralocorticoid Primary Mineralocorticoid excess Primary
activity Hyperaldosteronism
(adenoma, hyperplasia,
carcinoma)
Cushings disease
Exogenous
Mineralocorticoid
(fludrocortisone)
Hyperreninism (Renal
artery stenosis, Renin
producing tumor)
Glucocorticoid
remediable
hyperaldosteronism
Hypersecretion of
Deoxycorticosterone or
other mineralocorticoid
Licorice or other
mineralocorticoids
Liddle’s Syndrome
Amphotericin B
Hypomagnesemia
Increased distal delivery/flow Polyuria
Salt wasting nephropathies
Non kidney causes Vomiting (urinary K loss
contributes)
Diarrhoea
Dialysis
Table 27.6 Signs and symptoms of hypokalemia
Muscle weakness Starts with lower extremity and can progress to

trunk and upper extremity
Respiratory failure– respiratory muscle weakness
Intestinal Ileus (Pseudo-obstruction)
Rhabdomyolysis
Cardiac Arrhythmias ECG changes: Delayed Ventricular repolarization,
Depression of ST segment, decrease in amplitude
of T waves and increase in amplitude of U waves
(esp V4-V6)
Premature atrial or ventricular beats, sinus
bradycardia, atrioventricular blocks, Ventricular
tachycardia or ventricular fibrillation.
Treatment of Hypokalaemia steady state (Bartter, Gitelman, hyperaldosteron-

ism, stable diuretic doses with need for continued
The goals of treatment in hypokalemia are to pre- use) where supplementation is unlikely to correct
vent or treat life threatening complications the hypokalemia and hence potassium sparing
(arrhythmias, paralysis and rhabdomyolysis), diuretics (amiloride/triamterene) or mineralocor-
replace potassium loss (if actual deficit and not ticoid antagonists (spironolactone/ eplerenone)
due to transcellular shifts) and diagnose and treat are more appropriate. Another important aspect is
underlying cause. It is important to recognise the amount of potassium deficit (if not due to
whether the hypokalemia is due to transient transcellular shift) required to cause a serum
potassium loss (kidney or gastrointestinal) for potassium of 3 meq/L is 200–400 meq and
which potassium replenishment and resolution of 2 meq/L is 400–800 meq (Table 27.7).
underlying cause is appropriate or whether this a
548 G. B. Colbert.
Table 27.7 Treatment of hypokalemia
Principle Degree or cause Treatment

1. Prevent or treat Severe Hypokalemia Intravenous Potassium Chloride (20-40 meq/L of
life threatening saline solution or dextrose). Usually at rate not
complications more than 10 meq/hour (central vein).
Avoid dextrose if possible as this will increase

endogenous insulin and lead to transcellular shift of
potassium and worsen hypokalemia.
Additional oral potassium should be provided as

larger quantities can be provided through this
route. Likely deficit fora K of 3 meq/L is 200-400
meq and for a K of 2 meq/L is 400-800 meq.
Frequent monitoring is needed as ongoing losses
are not accounted in deficit estimate.
Mild - moderate Usually, oral potassium chloride of 60-80 meq/day.
Hypokalemia (3-3.5 However, larger amounts may be needed if
meq/L) potassium loss is expected to continue.
2. Diagnose and Low dietary intake Augment diet
correct underlying Transcellular shift Correct shift, supplement potassium only if severe
cause symptoms (eg: paralysis) as likely overshoot later.
Kidney Elimination
Diuretics Stop if possible, if ongoing need then add potassium
sparing diuretics
(amiloride/triamterene/spironolactone/eplerenone)
Mineralocorticoid Remove mineralocorticoid if possible (eg: adenoma,
licorice) or add Mineralocorticoid antagonist or
potassium sparing diuretic (amiloride/triamterene)
Supplementing with oral or IV potassium is unlikely
to significantly alter potassium as these patients are
at “steady state”
Hyperkalemia The signs and symptoms of hyperkalemia are

listed in Table 27.9.
Hyperkalemia results from increased potassium Treatment of hyperkalemia is focused on 3
out of the intracellular space and into the plasma steps: (Tables 27.10, 27.11)
space (Table 27.8). The vast majority of total
body potassium is intracellular. When potassium 1. If membrane instability (ECG changes as in
remains outside of the cell, hyperkalemia results Figure B) then stabilize the membrane (IV
without prompt ability of the body to eliminate calcium gluconate/calcium chloride)
the excess potassium. 2. Shift potassium intracellularly, if membrane
Potassium buffering: It is important to recog- instability and need time to implement/derive
nize the vital role played by buffering in daily benefit from step 3.
potassium management of the body (Figs. 27.3, 3. Remove potassium from body
27.4, 27.5).
Table 27.8 Causes of Hyperkalaemia
High potassium dietary (not usually sole cause)

intake
Transcellular shift of Decreased pH (Metabolic acidosis)
potassium Insulin deficiency
Beta- adrenergic blockade
Periodic paralysis
Cell lysis/Tissue catabolism
Severe exercise
Pseudohyperkalemia (during collection –
repeated clenching with tourniquet, hemolysis or
post collection – cell lysis)
Others:
Succinylcholine
Digitalis overdose
Decreased renal Impaired kidney excretion (acute or chronic)
excretion of potassium
Decreased Decreased RAAS: Hyporeninemic hypoaldosteronism
mineralocorticoid NSAIDS
activity ACE-inhibitors/ARBs
Calcineurin inhibitors
Decreased Adrenal Low cortisol (primary adrenal insufficiency,
synthesis : congenital adrenal hyperplasia)
Normal cortisol (heparin, isolated
hypoaldosteronism, post adrenal adenoma
removal)
Aldosterone Potassium sparing diuretics

resistance: Pseudohypoaldosteronism
Selective potassium secretion defects
Type 4 Renal Tubular Acidosis
Decreased distal delivery Volume depletion (true or effective)
NSAID: non-steroidal anti-inflammatory drugs, ACE: angiotensin converting enzyme, ARB: angiotensin receptor blocker
a Potassium Buffering
40 meq K–
3 orange juice
ICF ECF glasses
K+ K+
4-5 meq/L
140 meq/L
Na-K
ATPase
25 L 17 L
Fig. 27.3 Potassium Buffering 1. Figure represents the

potassium distribution of the body and the person is about
to drink 3 glasses of orange juice (net K load 40 meq)
550 G. B. Colbert.
Fig. 27.4 Potassium b Potassium Buffering

buffering II. Diagram
illustrates what would 40 meq K–
happen if there was no 3 orange juice glasses
buffering of the ICF ECF
potassium to the No Buffering:
intracellular K+ K+
compartment, significant 6.4-7.4
increase in potassium 140 meq/L
meq/L ECG:
and lead to bradycardia
as shown in the ECG
Na-K
ATPase
25 L 17 L
Fig. 27.5 Potassium c Potassium Buffering

Buffering III. Diagram
illustrates that buffering
due to the serum 40 meq K–
potassium level, Insulin 3 orange juice glasses
and catecholamines, ICF ECF
leads to a limited
increase in serum Buffering:
potassium K+ K+
4-5 meq/L
142 meq/L 1. Catecholamines
2. Insulin
3. Plasma K Concentration
Na-K
ATPase
25 L 17 L
Table 27.9 Signs and symptoms of hyperkalemia
Muscle Weakness Begins with lower extremity and ascends to trunk

and upper extremity
Paralysis
Cardiac Arrhythmia ECG Changes (Figure 3)
Sine-wave or cardiac standstill
Ventricular fibrillation
Asymptomatic
Table 27.10 Treatment of hyperkalemia
Step 1. Stabilize the IV calcium gluconate or Give if there are ECG changes as
membrane. Calcium Chloride demonstrated in Figure B. Continue to
(If no ECG changes and monitor ECG and continue to repeat calcium
hyperkalemia is not Usual dose 10ml of 10% every 5 minutes till ecg changes reversed.
severe, can skip step 1) calcium gluconate Calcium chloride has 3 times the calcium of
calcium gluconate but requires a central line
for administration
Step 2. Shift Potassium Glucose and insulin IV Impact starts in minutes, peaks at 1 hours
into the cell (to buy time and lasts 4-6 hours with a lowering of 0.5-
till step 3 can work) Usual Dose: 10 units of 1.5meq/L
regular insulin with 30-
If hyperkalemia is not 50gm of glucose (if hyperglycemia is present, can give insulin
severe and there is alone)
enough time for step 3 to Sodium Bicarbonate IV Impact starts in 1 hour and lasts 4-6 hours,
work, then can skip step with lowering of 0.5meq/L
2 Usual dose: 50meq given
over 5 mins Impact is low in patients with kidney failure
and those who don’t have metabolic acidosis
Beta 2 adrenergic Impact starts in 60-90 minutes and lasts 4-6
agonists (inhaled) hours with a lowering of 0.5-1.5 meq/L
Usual dose: anti- Tachycardia and angina can be precipitated

hyperkalemic dose is 10- and so avoid in active coronary disease
20mg of albuterol over 10
mins
Step 3. Removal from the Diuretics Loop or thiazide diuretics or their
body combination, if there is enough kidney
function
If not volume overloaded then may combine

with IVF (normal saline or bicarbonate) to
increase distal delivery
Cation exchange resins Sodium polystyrene, Patiromer, Sodium
zirconium cyclosilicate
Take time to act and need active gut

motility, risk of intestinal necrosis, hence
avoid in conditions listed in Table 7
Dialysis Treatment May be needed for those with limited or no
renal function
552 G. B. Colbert.
Table 27.11 Exchange resins for hyperkalemia
Potassium Binding Usual Dosing Exchanges Concerns

Agent
Sodium Polystyrene 15g given 1-4 times a Exchanges potassium Intestinal necrosis.
Sulfonate day for sodium. Electrolyte
abnormalities
Also binds magnesium (hypokalemia). Fluid
and calcium overload if sensitive to
sodium.
GI symptoms
Patiromer 8.4g daily and increase Exchanges potassium Hypomagnesemia,
dose in 8.4g for calcium. hypokalemia.
increments Also binds magnesium GI symptoms
Sodium Zirconium 10g thrice a day for Exchanges potassium Edema
Cyclosilicate first 48 hours, for hydrogen and Hypokalemia
maintenance doses sodium.
from 5g alternate day
to 15g daily (adjust in
5g increments)
Treatment of metabolic alkalosis should be

Metabolic Alkalosis targeted at two main causes, the source of bicar-
bonate generation and reversal of diminished kid-
Getting back to our patient with metabolic alka- ney excretion. Treating the underlying cause or
losis and a serum HCO3 38. Metabolic alkalosis condition is paramount if it is reversible. Limiting
is defined as a rise in serum bicarbonate concen- conditions of vomiting, excess gastric secretion
tration above 30 mEq/L, and usually accompa- removal, halting loop or thiazide diuretics can
nied by an increase in the serum pH. This state is make a quick impact. Gastric loss of acid can be
usually prevalent when two conditions occur: a treated with medications that reduce gastric acid
process leading to the increase in bicarbonate (HCl) secretion such as H2 blockers or proton
concentration, and a situation that prevents pump inhibitors that may improve serum alkalo-
excess bicarbonate excretion through the kid- sis. Exogenous sources and ingestions of alkali
neys [5]. Normal kidney function allows for should be stopped. Bicarbonate salts such as
complete excretion of excess bicarbonate that sodium bicarbonate or potassium bicarbonate
the body does not require to maintain pH around should be held, as well as any anions that are
the normal 7.40 range. Several processes metabolized to bicarbonate such as citrate or
increase serum bicarbonate concentration and lactate.
can be seen in Table 27.12. Some common situ- Kidney excretion of excess bicarbonate
ations are hydrogen loss from gastric secretions, should be optimized to return serum bicarbonate
excess urinary acid loss from diuretics in the kid- to normal levels. Restoring EABV will promote
ney, a shift of hydrogen ions into the cell, and bicarbonaturia, as well as correcting chloride
exogenous sodium bicarbonate or equivalent depletion, hypochloremia, and hypokalemia.
ingestion. Improvement in raising EABV is most effec-
Measurement of urine chloride levels can be tively achieved with chloride containing solu-
helpful to determine the etiology of metabolic tions such as isotonic saline 0.9% which not only
alkalosis (Table 27.13). restores volume but provides adequate chloride
Table 27.12 Common causes of metabolic alkalosis
Gastrointestinal acid Kidney acid loss Hypokalemia Alkali administration with Contraction
loss reduced kidney function alkalosis
Vomiting Primary Villous adenoma Calcium-alkali
mineralocorticoid syndrome
excess conditions
Gastric suction Licorice ingestion Malnutrition Bicarbonate infusion
Congenital chloride Liddle syndrome Laxative abuse Bicarbonate salt ingestions
diarrhea Apparent
mineralocorticoid
excess state
Loop or thiazide
diuretics
Bartter or Gitelman
syndrome
Post chronic
hypercarbia state
Table 27.13 Causes of metabolic alkalosis utilizing a urine chloride level
Low urine Chloride (<20 mEq/L) Normal Urine Chloride (>20 mEq/L)
Vomiting or nasogastric suction Primary hyperaldosteronism
Diuretic-induced alkalosis Liddle’s syndrome
Laxative abuse Excess licorice ingestion (glycyrrhizic acid)
Cystic fibrosis with sweat loss Apparent mineralocorticoid excess syndrome
Congenital chloride diarrhea Bartter syndrome
Gitelman syndrome
Hypokalemia
to the serum [6]. Improvement in heart failure, bicarbonate levels, dialysis may be needed to
nephrotic syndrome, and cirrhosis exacerbations remove the excess bicarbonate. Low bicarbonate
can improve effective blood volume out of the so baths are usually used but have a high floor usu-
called “third space”. Improving the EABV will ally much higher than a normal HCO3 of
restore the kidney’s ability to reduce reabsorp- 24 mEq/L. Continuous renal replacement therapy
tion of sodium and chloride and allow bicarbon- (CRRT) may be used as more tailored dialysate
ate losses in the urine. The increased filtrate baths are available that could contain lower
delivery to the distal tubule will allow acid amounts of sodium bicarbonate, and some prepa-
secretion through the type B intercalated cells as rations are made with sodium lactate. Severe and
well. Once this is achieved, bicarbonaturia can rare cases of metabolic alkalosis of bicarbonate
be measured with a urinary pH above 7 levels greater than 50 mEq/l and/or pH greater
(Table 27.14). than 7.55 may need acid infusion [7]. Intravenous
Patients with impaired kidney function have HCl or precursors such as ammonium chloride
great difficulty with bicarbonaturia generation. In can be infused as a 0.1 N(100 mEq/L) solution of
some patients with markedly elevated serum HCl in normal saline.
554 G. B. Colbert.
Table 27.14 Management of metabolic alkalosis
Source of HCO3 excess Treatments MOA Limitations

Vomiting Anti-emetic Limits gastric HCl loss Does not restore
medications and HCO3 generation volume lost
Gastric suction Stop suction Limits gastric HCl loss Does not restore
and HCo3 generation volume lost
H2 blocker or proton Limits gastric HCl loss Must tolerate oral
pump inhibitors and HCO3 generation therapy
Exogenous sources Stop bicarbonate salts Halts exogenous HCO3 May have stomach
(bicarbonate, citrate, excess upset if known
lactate) ulceration or GI disease
True volume depletion Restore volume with Halts HCO3 Need to avoid volume
intravenous and oral reclamation in overload
fluid proximal tubule,
- Recommend promotes
isotonic saline 0.9% bicarbonaturia
Inadequate EABV Correct disease Pulls volume into Disease severity is
exacerbations such as vascular space and variable and may not
heart failure, nephrotic improves oncotic be correctable
syndrome, cirrhosis pressure
Potassium chloride Offsets Cl losses May cause
hyperkalemia or
metabolic acidosis
Acetazolamide Carbonic anhydrase Sulfa based
inhibitor in proximal medication,
tubule of nephron hypokalemia, cannot
be used in cirrhosis,
chronic lung disease or
late stage CKD
Post hypercapnic Acetazolamide Carbonic anhydrase Sulfa based
metabolic state inhibitor in proximal medication,
tubule of nephron hypokalemia, cannot
be used in cirrhosis,
chronic lung disease or
late stage CKD
Life threatening Dialysis therapy Removes excess Need for dialysis
metabolic alkalosis bicarbonate catheter, machine, and
staffing resources, High
cost
Intravenous HCl or Offsets HCO3 by giving Necrosis of tissues,
ammonium chloride exogenous acid toxicity, metabolic
acidosis
Metabolic Acidosis ance, the lungs and kidneys work together to excrete
both these elements. The kidney must excrete acid
Metabolic acidosis is a frequent problem with as a combination of hydrogen ions with titratable
patients experiencing both acute kidney injury acids, particularly phosphate and ammonia.
(AKI) and chronic kidney disease (CKD). While Ammonia (NH3) conversion to ammonium NH4+
regional and cultural diets are highly variable, those is an adaptive response from metabolism of gluta-
consuming a typical Western Hemisphere diet con- mine and the process can be increased as needed
sume 15,000 mmol of carbon dioxide and during episodes of acid loading [8].
50–100 mEq of nonvolatile acid are produced each Metabolic acidosis is defined as a process that
day. To maintain appropriate serum acid-base bal- increases the concentration of hydrogen ions in
the body, thus lowering the bicarbonate concen- mon mnemonic used to list the causes of an anion
tration. Acidemia is defined as a lower arterial gap metabolic acidosis is GOLDMARK [10].
serum pH <7.35, which can result from patho- Treatment recommendations vary depending
logic processes of metabolic acidosis, respiratory on the disease state or condition leading to the
acidosis, or both. Metabolic acidosis can be mea- acidosis. Underlying conditions of diabetic keto-
sured with a low serum bicarbonate usually acidosis, lactic acidosis, acute kidney injury, or
<23 mEq/L [9]. Interestingly not every patient diarrheal illness should be corrected as they may
with a metabolic acidosis will have a lower arte- be the primary causes of the acidosis. Ingestions
rial pH. Both the pH and hydrogen ion concentra- such as aspirin, methanol and ethylene glycol
tion depend upon the coexistence of other should be stopped once recognized. Acute meta-
acid-base disorders. Therefore, the pH in each bolic acidosis and chronic metabolic acidosis are
individual patient will vary depending on the level generally treated as separate entities. Acute met-
of metabolic acidosis and other clinical factors. abolic acidosis should be treated with bicarbon-
While the pathophysiology of each is beyond ate therapy with severe acidemia indicated by a
the scope of this chapter, treatment depends on pH <7.1. It is also suggested to treat with bicar-
determining which category is leading to the aci- bonate if pH <7.2 in patients who have severe
dotic state. Causes of metabolic acidosis, sepa- AKI, as there may be survival and kidney func-
rated as those causing an anion gap and those tion improvement. Clinical impact of treating
without a gap, are listed in Table 27.15. A com- severe acute metabolic acidosis remains contro-
Table 27.15 Causes of metabolic acidosis both anion gap and normal gap
Mechanism of acidosis Increased Anion Gap Normal Anion Gap

Increased acid production Lactic acidosis
Ketoacidosis
Diabetes Mellitus
Starvation
Alcohol
D-Lactic acidosis Potential co-existence due to
urinary D-lactate as Na and K
salts
Ingestions Ethylene glycol
Aspirin
Methanol
Toluene Toluene
Diethylene glycol
Propylene glycol
Pyroglutamic acid (5-
oxoproline)
Loss of bicarbonate Diarrhea or GI losses
Type II RTA (proximal)
Post Treatment of ketoacidosis
Carbonic anhydrase inhibitors
Ureteral diversion
Decreased renal acid excretion Chronic kidney disease Nephron damage (but
preserved eGFR)
Type I RTA (distal)
Type IV RTA
(hypoaldosteronism)
556 G. B. Colbert.
versial due to conflicting data. Most studies of accommodate acid loading, but when kidney
sick patients with acute MA have been from ani- function is impaired, or gastrointestinal bicar-
mal or tissue experiments, while human studies bonate losses are high, the serum pH and HCO3
of cardiovascular benefits have not been repli- balance can quickly become out of homeosta-
cated. Still many clinicians agree that starting sis. Treatment of existing underlying conditions
bicarbonate therapy when measured serum combined with the appropriate therapy of alka-
HCO3 is <5 meq/L with pH below 7.1 is line solution can improve serum HCO3, raise
prudent. pH to normal levels, and improve long term
Bicarbonate therapy is administered in the clinical status of patients.
form of oral sodium bicarbonate tablets, baking
soda powder, or intravenous sodium bicarbonate
diluted in a hypotonic solution. NaHCO3 is the Conclusions
most commonly used alkalinizing agent, as com-
pared with giving lactate, citrate, potassium Returning to the patient at the beginning of the
bicarbonate, or ketoacid anions (Table 27.16). chapter—the 48-year-old man with a past medi-
Intravenous sodium bicarbonate is usually deliv- cal history of Heart Failure with Reduced
ered as 8.4 percent (50 mEq/50 mL) 50 mL vials Ejection Fraction (HFrEF) 25%, and Chronic
or ampules. It is expected that if normal body Kidney Disease Stage G3, who has been strug-
water weight is present, one 50 mEq/L vial will gling with volume overload, and had recently
raise the HCO3 concentration between 1.3 and been prescribed an increased dose of his loop
1.5 mEq/L in a patient weighing 70 kg. If more diuretic. Whilst his 10 kg weight loss is reflected
than 1 vial is to be administered, hypotonic water in the improvement in his edema, he has noted
solution should be used to avoid hypernatremia large volumes of urination, and concomitant
as the bicarbonate will deliver a large quantity of increased fatigue. The case, and his blood test
sodium. results highlight the importance of understanding
Treating chronic metabolic acidosis is less that the likely cause of his hyponatremia is a
controversial as there are known consequences in result of an inability to excrete free water, and
patients with CKD including decreased muscle may be exacerbated by his diuretics. This is fre-
mass, bone health, and worsening eGFR. For quently seen amongst CKD patients with heart
long term maintenance treatment, potassium salts failure. His hypokalemia and metabolic alkalosis
with bicarbonate can be effective for patients are also frequent complications of loop diuretic
with hypokalemia. use.
Metabolic acidosis exists as both an acute Broadly, understanding electrolyte and acid
and chronic problem. Patients usually can base disorders requires a thorough assessment of
Table 27.16 Oral alkali preparations for treating metabolic acidosis
Product Concentration Base Concentration

Potassium Citrate (Polycitra) 500 mg per 5 mL 2 mEq per 1 mL
Sodium Bicarbonate 325 or 650 mg tablets 4 mEq per 325 mg tablet
Citric Acid 140 g per 1000 mL 1 mEq per 1 mL
(Shohl’s Solution)
Sodium Citrate (Bicitra) 500 mg/334 mg per 5 mL 1 mEq per 1 mL
Baking Soda (sodium 1 tsp, 5000 mg powder 60 mEq per tsp
bicarbonate)
Enteric coated Sodium 650 or 1300 mg tablets 8 mEq per 650 mg tablet
Bicarbonate (Bicarbi)
the likely cause, which in turn will direct the best E. “Ecstasy” intoxication—Correct. Ecstasy
approach to treatment. causes a SAIDH picture with ADH
release leading to inappropriately con-
centrated urine osmolality. Additionally,
Questions frequently at parties young people are
encouraged to drink fluids such as alco-
hol, water, and flavored drinks leading to
1. A 21-year-old woman is brought to the further hypotonic ingestion.
Emergency Department (ED) after she suf- 2. A 32-year-old man is referred for evaluation
fered a tonic-clonic seizure outside of a party. of hypertension. He believes that his hyper-
She has no significant medical history and tension was first diagnosed at age 15 but he
takes no medications. Friends who also was never told what the etiology may be. Of
attended the party reported that “recre- note, his father died at age 43 with a stroke,
ational” drugs were at the party. On arrival to and he has a brother age 25 with hyperten-
the ED, her vital signs were notable for a sion. On physical examination, he is normal
temperature of 38.6 °C, pulse of 89 beats/ appearing with a blood pressure of
min, and blood pressure of 141/76 mmHg. 182/90 mmHg, and his fundoscopic exami-
Her examination was notable for some nation reveals mild arteriolar narrowing.
confusion and lethargy. Otherwise, her phys- There are no abdominal bruits. Laboratory
ical examination was within normal limits. studies revealed: Serum sodium: 145 mEq/L
Laboratory studies revealed: Serum Serum potassium: 3.0 mEq/L Serum chlo-
sodium: 121 mEq/L Serum potassium: ride: 108 mEq/L Serum bicarbonate:
4.3 mEq/L Serum bicarbonate: 21 mEq/L 30 mEq/L Serum creatinine: 1.1 mg/dL
Serum chloride: 92 mEq/L Urine osmolality: Urine potassium: 90 mEq/24 h Plasma aldo-
466 mOsm/kg sterone: 7 ng/dL Plasma renin activity: 0.6
Which of the following is the MOST Which of the following would be the
likely etiology of this patient’s presenting MOST likely cause of his hypertension and
symptoms and laboratory findings? associated laboratory findings?
A. Primary polydipsia A. Gordon’s syndrome
B. Synthetic marijuana B. Liddle’s syndrome
C. “Bath Salt” intoxication C. Bartter’s syndrome
D. Cocaine intoxication D. Gitelman’s syndrome
E. “Ecstasy” intoxication E. Primary hyperaldosteronism
Answer: E. “Ecstasy” intoxication Answer: B Liddle’s Syndrome
A. Primary polydipsia—Incorrect. A patient A. Gordon’s syndrome—Incorrect. This
with primary polydipsia should have a syndrome is associated with hyperkale-
very dilute urine in the acute setting of mia, hypertension and metabolic
water intoxication with urine osmolality acidosis
less than 100 mOsn/kg B. Liddle’s syndrome—Correct. This syn-
B. Synthetic marijuana—Incorrect. This is drome is associated with normal or sup-
not associated with hyponatremia with pressed plasma aldosterone and renin as
elevated urine osmolality there is inappropriate uptake of urine
C. “Bath Salt” intoxication—Incorrect. This sodium at the distal tubule. Patients fre-
is not associated with hyponatremia with quently have hypertension, hypokalemia,
elevated urine osmolality and normal or suppressed plasma and
D. Cocaine intoxication Incorrect. This is renin levels
not associated with hyponatremia with C. Bartter’s syndrome—Incorrect. This syn-
elevated urine osmolality drome is associated with hypokalemia,
558 G. B. Colbert.
hypotension, and increased serum renin 4. A 67-year-old man with bipolar disorder man-
and aldosterone levels aged for 25 years with lithium carbonate is
D. Gitelman’s syndrome—Incorrect. This admitted for acute appendicitis. Post
syndrome is associated with hypokale- operatively, his urine output is replaced milli-
mia, hypotension, increased serum renin liter for milliliter with 0.9% saline. The next
and aldosterone levels, and day, he is lethargic, and his serum sodium
hypercalcemia concentration is found to be 162 mEq/L.
E. Primary hyperaldosteronism—Incorrect. Which of the following about his condi-
This syndrome is associated with a high tion is TRUE?
aldosterone level and suppressed renin A. Lithium is not associated with
leading to an elevated aldosterone renin hypernatremia
ratio (ARR). B. A patient on lithium only has electrolyte
3. A 60-year-old man undergoes neurosurgery changes in early stages
for a craniopharyngioma. Postoperatively, C. The patient will likely have a very con-
his urine output is noted to be high for 2 days, centrated urine
and he is given two doses of intravenous des- D. The patient should have hypotonic fluid
mopressin. Replacement doses of hydrocor- given now such as 0.45% saline
tisone are prescribed, and he is discharged E. 0.9% normal saline is an appropriate
from the hospital. Two days later, he is read- fluid to give a patient with
mitted with lethargy and a serum sodium of hypernatremia
118 mEq/L. Answer D: The patient should have hypotonic
Which of the following is the MOST fluid given now such as 0.45% saline
likely cause of the hyponatremia? A. Lithium is not associated with hyperna-
A. Mineralocorticoid deficiency tremia- Incorrect. Lithium frequently is
B. A persistent effect of desmopressin associated with hypernatremia as it
C. Adrenocorticotropic hormone (ACTH) causes a nephrogenic diabetes insipidus
deficiency B. A patient on lithium only has electrolyte
D. Degenerating hypothalamic neurons changes in early stages—Incorrect.
Answer: D. Degenerating hypothalamic Lithium is most associated with electrolyte
neurons changes in the chronic setting of exposure
A. Mineralocorticoid deficiency—Incorrect. The patient will likely have a very
No evidence related to deficiency with concentrated urine—Incorrect. The
clinic picture patient is likely to have a dilute urine as
B. A persistent effect of desmopressin— lithium leads to an insufficient concen-
Incorrect. Desmopressin last for less than trating defect and nephrogenic diabetes
12 hours whether endogenous or insipidus
exogenous. C. The patient should have hypotonic fluid
C. Adrenocorticotropic hormone (ACTH) given now such as 0.45% saline—
deficiency—Incorrect. ACTH deficiency Correct. The patient cannot concentrate
would not cause hyponatremia this urine correctly and is needing a hypo-
quickly in a patient who can tolerate a tonic fluid replacement to return serum
diet and consume appropriate fluids. sodium back to normal range
D. Degenerating hypothalamic neurons— D. 0.9% normal saline is an appropriate
Correct. Desmopressin hormone is stored fluid to give a patient with hypernatre-
in the posterior pituitary. During surgery mia—Incorrect. 0.9% sodium has a Na
causing injury, the pituitary necroses and of 154 mEq/L and therefore does not
slowly releases the desmopressin stored have the best capacity to bring serum
likely causing the hyponatremia. sodium into normal range. A hypotonic
fluid is more appropriate and effect per Which oral potassium binder or treatment
mL of volume. does not expose the patient to further sodium
5. A 32-year-old pregnant woman is being loading?
treated for pre-eclampsia and is noted to A. Patiromer
have a serum calcium of 7.5 mg/dL and a B. Sodium zirconium cyclosilicate
serum phosphate of 5.3 mg/dL, with a nor- C. Polystyrene sulfonate (Kayexalate)
mal serum albumin. She has a BUN of 21 D. Normal saline IV push with furosemide
and a creatinine of 1.9 mg/dL. treatment
Which of the following is the likely cause E. Sodium bicarbonate
of the hypocalcemia? Answer: Patiromer
A. Chronic kidney disease A. Patiromer—Correct. The only oral potas-
B. Hyperphosphatemia sium binder not bound to sodium.
C. Hypermagnesemia Patiromer is bound with calcium.
D. Hyperkalemia B. Sodium zirconium cyclosilicate—
E. Hypernatremia Incorrect. This potassium binder is bound
Answer: C Hypermagnesemia with sodium.
A. Chronic kidney disease—Incorrect. This C. Polystyrene sulfonate—Incorrect. This
is not the best answer as Cr is not suffi- potassium binder is bound with sodium.
ciently high to be associated with a late D. Normal saline IV push with furosemide
stage CKD which is associated with treatment- Incorrect—Normal saline has
hypocalcemia 9 g of sodium per 1 L bag.
B. Hyperphosphatemia—Incorrect. The E. Sodium bicarbonate—Incorrect. Sodium
phosphate level in this patient is within bicarbonate is bound with sodium
the upper limits of normal. 7. A 24 year old woman presents to the emer-
C. Hypermagnesemia—Correct. Patients gency room with altered mental status. Her
with preeclampsia are frequently placed initial labs are drawn and she is found to have
on a magnesium infusion as prevent of an anion gap of 22. Which medical condition
moving into eclampsia. This patient or ingestion is not associated with a high
likely has an undiagnosed elevated serum anion gap acidosis?
magnesium leading to hypocalcemia. A. Ethylene glycol
D. Hyperkalemia—Incorrect. Hyperkalemia B. Diabetic ketoacidosis
does not directly cause hypocalcemia C. Isopropyl alcohol
and would not correlate with the clinical D. Metformin overdose
scenario E. Acetaminophen overdose
E. Hypernatremia—Incorrect. Hyper Answer: Isopropyl alcohol
natremia does not directly cause hypo- A. Ethylene glycol—Incorrect. This inges-
calcemia and would not correlate with tion causes a high AG and is frequently
the clinical scenario ingested accidentally or during a suicide
6. A 38 year man with heart failure with reduced attempt.
ejection fraction, CKD stage IV presents to B. Diabetic ketoacidosis—Incorrect.
clinic for follow up. He has lower extremity Ketoacidosis leads to a high anion gap
edema on exam and mild rales at the bases of and is part of the GOLDMARK acronym
his lungs on auscultation. You advise the for AG diagnoses.
patient based on guidelines to maintain a C. Isopropyl alcohol—Correct. Isopropyl
2400 mg/day sodium restriction. He is on alcohol is not associated with a high
Lisinopril 50 mg, Furosemide 20 mg twice a anion gap but causes an elevated osmolar
day, carvedilol at 12.5 mg twice a day. Labs gap.
show Na 136 mEq/L, K 5.7 mEq/L, HCO3 D. Metformin overdose—Incorrect. Metfor
21 mEq/L and Cr 2.8 mg/dL. min overdose leads to lactic acidosis type
560 G. B. Colbert.
B. Lactic acidosis causes a high anion A. Amlodipine—Incorrect. Calcium chan-

gap. nel blockers are not commonly associ-
E. Acetaminophen overdose—Incorrect. ated with hyponatremia.
Acetaminophen is associated with a high B. S p i r o n o l a c t o n e — I n c o r r e c t .
anion gap due to propylene glycol. Spironolactone is not commonly associ-
8. A 32 year old man presents to CKD clinic for ated with hyponatremia.
follow up. He has CKD Stage V and suffer- C. Hydrochlorothiazide—Correct. Thiazide
ing with chronic metabolic acidosis. His and thiazide like diuretics are associated
serum HCO3 is 17 mEq/L on recent lab. He is with hyponatremia. Usually this is
started on Sodium bicarbonate therapy twice reversible once the medication is stopped.
a day and on follow up 3 months later his D. Losartan—Incorrect. Angiotensin recep-
serum bicarbonate level has improved to tor blockers are not commonly associ-
22 mEq/L. Which therapeutic advantages ated with hyponatremia.
with his improving acidotic state will the E. Carvedilol—Incorrect. Beta blockers are
patient experience? not commonly associated with
A. Lower Mortality hyponatremia.
B. Improved bone strength 10. A 29 year old woman presents to the emer-
C. Slower eGFR loss gency room with altered mental status. Her
D. Hyperkalemia prevention Na is 109 mEq/L, K 2.9 mEq/L and Cr
E. All of the above 0.7 mg/dL. You determine that you would
Answer: E. All of the Above like to give her a 3% saline bolus to improve
A. Lower mortality—Incorrect. Lower mor- her serum sodium level and improve mental
tality is associated with improving acido- status. During the initial phase of hyponatre-
sis but is not the only correct answer. mia treatment, what is the recommended rate
B. Improved bone strength. Incorrect. of rise in the first 24 h to prevent osmotic
Improved bone strength is associated demyleniation syndrome (ODS)?
with improving acidosis but is not the A. 2–4 mEq/L rise in serum Na
only correct answer. B. 4–6 mEq/L rise in serum Na
C. Slower eGFR loss—Incorrect. This C. 8–10 mEq/L rise in serum Na
answer is associated with improving D. 10–12 mEq/L rise in serum Na
acidosis but is not the only correct E. No limitation is recommended
answer. Answer: B. 4-6 mEq/L rise in serum Na
D. Hyperkalemia prevention—Incorrect. A. 2–4 mEq/L rise in serum Na—Incorrect.
Hyperkalemia prevention is associated A rise of 6 mEq/L is usually considered
with improving acidosis but is not the safe to prevent ODS symptoms while
only correct answer. still allowing mental status symptoms to
E. All of the above—Correct. All answer improve. This is too low.
choices are correct. B. 4–6 mEq/L rise in serum Na—Correct. A
9. Which anti-hypertensive treatment is associ- rise of 6 mEq/L is usually considered
ated with hyponatremia in some patients? safe to prevent ODS symptoms while
A. Amlodipine still allowing mental status symptoms to
B. Spironolactone improve.
C. Hydrochlorothiazide C. 8–10 mEq/L rise in serum Na—Incorrect.
D. Losartan A rise of this magnitude in the first 24 h
E. Carvedilol of treatment has been shown to be associ-
Answer: C. Hydrochlorothiazide ated with ODS symptoms.
D. 10–12 mEq/L rise in serum Na— guideline on diagnosis and treatment of hyponatrae-
mia. Eur J Endocrinol. 2014;170(3):G1–47. https://
Incorrect. A rise of this magnitude in the doi.org/10.1530/EJE-13-1020. Erratum in: Eur J
first 24 h of treatment has been shown to Endocrinol. 2014 Jul;171(1):X1.
be associated with ODS symptoms. 3. Edelman IS, Leibman J, O’Meara MP, Birkenfeld
E. No limitation is recommended— LW. Interrelations between serum sodium concen-
tration, serum osmolarity and total exchangeable
Incorrect. Uncontrolled rise of sodium in sodium, total exchangeable potassium and total body
hyponatremia is directly related to ODS water. J Clin Invest. 1958;37(9):1236–56. https://doi.
symptoms. org/10.1172/JCI103712.
4. Kraut JA, Madias NE. Re-evaluation of the normal
range of serum total CO2 concentration. Clin J Am
Test your learning and check your understand- Soc Nephrol. 2018;13(2):343–7.
ing of this book’s contents: use the “Springer 5. Furst H, Hallows KR, Post J, Chen S, Kotzker W,
Nature Flashcards” app to access questions using Goldfarb S, Ziyadeh FN, Neilson EG. The urine/
https://sn.pub/cz9Cok. To use the app, please fol- plasma electrolyte ratio: a predictive guide to water
restriction. Am J Med Sci. 2000;319(4):240–4.
low the instructions in Chap. 1. https://doi.org/10.1097/00000441-200004000-00007.
6. Schwartz WB, Ypersele V, de Strihou KJP. Role of
anions in metabolic alkalosis and potassium defi-
ciency. N Engl J Med. 1968;279(12):630–9.
7. Mehta AN, Emmett JB, Emmett M. GOLD MARK:
References an anion gap mnemonic for the 21st century. Lancet.
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1. Verbalis JG, Goldsmith SR, Greenberg A, Korzelius 8. Luke RG, Galla JH. It is chloride depletion alkalo-
C, Schrier RW, Sterns RH, Thompson CJ. Diagnosis, sis, not contraction alkalosis. J Am Soc Nephrol.
evaluation, and treatment of hyponatremia: expert 2012;23(2):204–7.
panel recommendations. Am J Med. 2013;126(10 9. Frick PG, Senning A. The treatment of severe meta-
Suppl 1):S1–42. https://doi.org/10.1016/j. bolic alkalosis with intravenous N /10 or N /5 hydro-
amjmed.2013.07.006. chloric acid. Germ Med Monthly. 1964;9:242.
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S, Bichet D, Decaux G, Fenske W, Hoorn EJ, Ichai Verzola D, Vettore M, Russo R, Procopio V, Deferrari
C, Joannidis M, Soupart A, Zietse R, Haller M, van G, Tessari P. Kidney protein dynamics and ammonia-
der Veer S, Van Biesen W, Nagler E, Hyponatraemia genesis in humans with chronic metabolic acidosis. J
Guideline Development Group. Clinical practice Am Soc Nephrol. 2004;15(6):1606–15.
The Role of Renal Registries
28
Mogamat Razeen Davids , Fergus J. Caskey ,
and John B. Eastwood
Clinical Scenario ure (end stage kidney disease/ESKD), which is

A 54-year-old male haemodialysis patient, with being treated with kidney replacement therapy
end stage kidney disease secondary to diabetes (KRT) [1].
mellitus, has recently learned that data from all National kidney disease registries provide valu-
kidney patients in the unit are being sent to a able information, that can inform the planning of
national database. At his next clinic appointment, services for kidney care and enhance the argu-
he asks what is happening to his data. ments for better resource allocation. They also
What will you say? allow audit of the delivery and quality of care, and
the monitoring of the impact of interventions.
Most registries focus on patients with kidney fail-
Introduction ure who are treated with KRT, especially dialysis,
and there are few countries with registries for
The combined burdens of non-communicable chronic kidney disease (CKD) or AKI.
diseases, infectious diseases, exposure to envi- In this chapter, we give a brief overview of
ronmental toxins and acute kidney injury (AKI) renal registries in different parts of the world,
related to trauma and childbirth are driving a describe the elements involved in establishing a
global epidemic of kidney disease. It is estimated renal registry, consider the research questions
that there are over 850 million people worldwide which could be addressed by renal registries and
who have kidney disease, and approximately describe examples of the impact of registry data
3.9 million of these individuals have kidney fail- on clinical practice and access to kidney care.
M. R. Davids (*)
Division of Nephrology, Stellenbosch University and Renal Registries Around the World
Tygerberg Hospital, Cape Town, South Africa
e-mail: mrd@sun.ac.za
Most developed countries have national renal
F. J. Caskey registries, that provide critical information to
Population Health Sciences, University of Bristol,
Bristol, UK support the planning, delivery and evaluation of
e-mail: fergus.caskey@bristol.ac.uk dialysis and transplantation services. The
J. B. Eastwood European Renal Association (ERA) Registry is
Department of Renal Medicine, Institute of Medical the world’s oldest renal registry and was started
and Biomedical Education, St. George’s, University in 1964 [2, 3]. The ERA Registry publishes an
of London, London, UK annual report and several scientific papers each
e-mail: jbeastwo@sgul.ac.uk
https://doi.org/10.1007/978-3-031-09131-5_28
564 M. R. Davids et al.
year. It also offers courses in epidemiology and been published mainly by North African coun-
training in data analysis. tries, starting with Egypt and Tunisia in 1975,
Many other registries have followed, includ- followed by South Africa in 1977, and thereaf-
ing the Australia and New Zealand Dialysis and ter by Libya, Algeria and Morocco. Most of
Transplant Registry (ANZDATA, established in these registries failed due to resource con-
1977), the Canadian Organ Replacement Register straints, and in recent years only the re-estab-
(CORR, 1981), the Japanese registry (1983) [4], lished South African Renal Registry [6, 7] has
the United States Renal Data System (USRDS, published regular reports, starting with its anal-
1988), the Scottish Renal Registry (1991), the ysis of 2012 data. In 2015, the African
Malaysian Renal Registry (1992) and the UK Association of Nephrology (AFRAN) estab-
Renal Registry (1995). lished the African Renal Registry [8] and to
The international comparisons chapter of the date, six countries have joined this initiative
US Renal Data System annual report is an excel- and are using its online data capture platform.
lent resource, which collates information on the The International Society of Nephrology
treatment of kidney failure worldwide [5]. The (ISN) has a project under its advocacy theme
highest annual incidences of treated kidney fail- called SHARing Expertise to support the set-up
ure in 2018 were reported from Jalisco, Mexico of Renal Registries (SharE-RR) [9]. SharE-RR
(594 per million population (pmp)), Taiwan supports countries without registries and pro-
(523 pmp), Hungary (508 pmp) and the US (395 motes shared learning among countries with
pmp). The lowest rates were reported from established surveillance systems. One of its first
South Africa (16 pmp), Ukraine (40 pmp) and activities was to conduct a survey of kidney
Bangladesh (61 pmp). The highest prevalence health surveillance systems. Of the 85 respond-
rates in 2018 were from Taiwan (3587 pmp), ing organisations (Fig. 28.1), 99% collected
Japan (2653 pmp), the US (2354 pmp) and adult haemodialysis data, 92% collected perito-
Singapore (2255 pmp). The lowest rates were neal dialysis data and 74% collected transplant
reported from Bangladesh (119 pmp), South data. Paediatric haemodialysis, peritoneal dialy-
Africa (186 pmp) and Ukraine (227 pmp). sis and transplant data were collected by 75%,
The lack of renal registries in many low- and 66% and 60%, respectively. Data on CKD were
middle-income countries means that there are collected by 22% and data on AKI by 9%,
few reliable statistics on kidney failure and respectively [9].
KRT. For example, in Africa, registry data have
28 The Role of Renal Registries 565
Fig. 28.1 Countries reporting renal registries in the Latinoamericana de Nefrología e Hipertensión, SLANH;
SHARing Expertise to support the set-up of Renal yellow), Europe (European Renal Association, ERA;
Registries (SharE-RR) survey. Dark blue indicates blue) and Africa (African Association of Nephrology,
countries with registries. The inset shows coverage of the AFRAN; green). From Hole et al. [9].
regional registries in South America (Sociedad
will not be the same as the incidence of kidney

hich Questions Can Be Answered
W failure, because of the variable access to dialysis
by Renal Registries? and transplantation services. The prevalence of
KRT is determined by the burden of the disease,
Renal registries collect a well-defined set of access to treatment and survival on KRT. The
health and demographic data with the aim of gen- extremely wide variation in reported prevalence
erating information on the main causes and the is mainly a reflection of differing access to dialy-
incidence of kidney failure, and information on sis and transplantation [11]. This is particularly
the prevalence, treatment and outcomes of relevant in LMICs, where transplantation ser-
patients on KRT. Table 28.1 summarises the vices are limited, and where dialysis may have to
questions that might be readily answered using paid for out of pocket by patients and their fami-
data collected by renal registries. lies [11]. Most patients in such a situation are
In most countries, especially low- and middle- unable to afford dialysis treatments beyond the
income countries (LMICs), the incidence of KRT first few months [12].
Table 28.1 Some questions that can be addressed by renal registries. Focused on patients with kidney failure (stage
5 CKD/ESKD). Adapted from Davids et al. [10]
Epidemiology of kidney failure
– incidence of CKD stage 5
– incidence of patients accessing KRT
– aetiology
– prevalence of KRT
– KRT modalities
Patient characteristics and disparities in access to KRT
– age, sex, ethnicity
– comorbid diseases—diabetes, infections with HIV, hepatitis B or hepatitis C
– geography—urban/rural, regional/provincial disparities
– socio-economic status, medical insurance, access to private vs. public sector services
– access to medications such as erythropoietin, intravenous iron, immunosuppressive agents
Primary outcomes
– patient survival
– modality/technique survival
Other outcomes
– causes of death or reasons for cessation of treatment
– hospitalisations
– dialysis adequacy
– vascular access in HD patients
– laboratory data such as those related to anaemia management, bone-mineral disease, etc.
– rejection episodes in transplant patients
Patient-reported outcomes
– quality of life
– employment
– travelling and distances to treatment centres
Outcomes in sub-populations of interest
– children
– the elderly
– people with HIV
– people treated with supportive/palliative care, without KRT
Abbreviations: HD, haemodialysis; HIV, human immunodeficiency virus; KRT, kidney replacement therapy; PD, peri-
toneal dialysis
to be clear. Registry teams usually include

Establishing Renal Registries
nephrologists, data managers and data capturers,
epidemiologists or statisticians, administrators
Information for nephrologists or nephrology
and software developers/database managers.
societies wanting to establish a renal registry is
Some registries also employ nurses or unpaid
available via the SharE-RR pages on the ISN
volunteers [9]. Advisory committees may include
website (https://www.theisn.org/initiatives/data-
patient representatives, and representatives from
collection/#SharE-RR). Some of the important
industry and funding organisations.
elements to consider when starting a new registry
are briefly mentioned below [8, 9].
larifying the Purpose, Scope

C
Identifying Stakeholders and Minimum Outputs
and Building the Registry Team
The purpose is usually to generate information on
Renal registries are often established by national the prevalence, incidence and causes of kidney
nephrology societies, with the support of govern- failure in patients on KRT and, to a variable extent,
ment. The governance and oversight plans need additional information on the treatment and out-
comes. A small set of epidemiologic data is col- Definitions should conform to those used by
lected over many years. Unnecessary complexity well-established registries to facilitate compari-
should be avoided, as this will drive up costs and sons and to allow the aggregation of data. For
decrease compliance with data submission. example, the coding of the primary kidney dis-
ease should use an established system such as the
ERA Registry coding scheme [13].
Defining and Finding Cases
All patients who receive KRT for kidney failure ollecting Data and Ensuring Data
C
should be included, including those who do not Quality
survive to 90 days. It is important to report on those
patients who discontinue dialysis for financial rea- This is the most resource-intensive aspect of run-
sons and those “crash landers” who present very ning a registry. Well-documented processes
late and die soon after commencing KRT. The use should guide data collection and ensure data
of multiple sources of information increases com- quality. Where possible, data should be collected
pleteness and may include the patient’s doctor, directly from health information systems. Quality
treatment centres, laboratories, funders, and suppli- control must focus on data completeness, the pre-
ers of medications or consumables. vention of duplicates, validity and accuracy,
timeliness, usefulness of items and the accuracy
of data interpretation and reporting [14].
Minimum Dataset and the Data
A
Dictionary
ata Ownership and Access,
D
Many registries focus their annual follow-up data and Dissemination of Findings
collection on 31 December. A typical minimum
dataset would include the following: The question of who owns the data should be
clarified at the start. Making anonymised
• Country, region and centre information widely available is a principle com-
• Patient unique identification number and mon to many registries and requires data access
name and publication policies for responding to
• Date of birth and sex requests for data while safeguarding patient con-
• Primary kidney disease fidentiality. Routine outputs might include annual
• Date and modality of first treatment reports, presentations at academic meetings, pub-
• Changes of doctor, centre lications in medical journals and the release of
• Current treatment modality datasets.
• Changes of treatment modality since last cen-
sus, including cessation of treatment or loss to
follow-up Ethical Considerations
• Death details
Consideration of ethical aspects and privacy and
Optional data might include more aspects of the data protection legislation is extremely important
treatment, indicators of treatment quality and for registries. Many registries have obtained
additional outcomes such as hospitalisations and waivers of individual informed consent to facili-
quality of life. tate including all patients in the registry while
The data dictionary describes the elements to taking the necessary precautions to protect
be collected and specifies the data type (categori- patients’ personal information. Examples include
cal, numerical), precision (number of decimal the UK, Scottish, French and South African
points), range of acceptable values, etc. registries.
Impact of Registries geographically, culturally and economically sim-

ilar neighbours, challenging treatment modality
Improving Access to Care preferences and highlighting the importance of
primary and secondary prevention in CKD [19].
Renal registries can aid efforts to prevent, detect In South Africa, the first report of the re-
and treat the earlier stages of CKD by identifying established South African Renal Registry [6]
the most important causes of kidney failure in revealed a markedly uneven distribution of KRT
each country. Where access to treatment is across provinces and large differences in preva-
restricted on economic grounds, registry data can lence rates between the resource-constrained
highlight disparities in the provision of KRT ser- public healthcare sector and the well-resourced
vices within and between countries. This may private sector (73 vs. 620 pmp). This generated
encourage governments and other funders to prominent media coverage and led to the national
increase their support. Registries can identify health minister convening a summit on “An
sub-groups with reduced access to treatment or effective approach to chronic kidney disease in
poor outcomes and monitor the adoption and South Africa”, in 2015. It is hoped that a compre-
impact of evidence-based interventions. A few hensive approach and more resources will even-
examples of the impact of renal registries are pro- tually flow from this initiative. More recently,
vided below. Jardine et al. [20] have used registry data to dem-
The Tunisian dialysis registry has had a major onstrate that the 1-year survival of incident
impact on the country's development of KRT South African patients on KRT (90.4%) is com-
[15]. Registry data influenced decisions to parable with that of better-resourced countries.
increase the number of nephrologists, develop a There was no difference in survival between
new transplant programme, start new dialysis patients treated in the public and private sectors
units and develop a kidney disease prevention and the authors argue that these findings should
programme. The rate of new patients starting encourage government to increase access to
KRT in Tunisia increased from 82 pmp in 1992–3 KRT in the public sector.
to 159 pmp in 2000–1.
The Thailand Renal Replacement Therapy
Registry was instrumental in building the case for mbedding Interventional Studies
E
their “PD First” programme [16], which saw a in Renal Registries
marked increase in access to peritoneal dialysis
as the initial modality of treatment. The registry Traditional clinical trials have become increasingly
provided essential quality assurance data on peri- expensive and may have limited generalisability
tonitis rates and peritoneal dialysis technique sur- among the populations of patients on KRT. A more
vival [17]. pragmatic approach is now being adopted that
The National Renal Registry of the Malaysian makes better use of routine data, such as that col-
Society of Nephrology reports on treatment lected by renal registries [21]. Registries may be
rates and modality, quality standards, patient used to identify potentially eligible participants,
reported outcomes and kidney biopsy data. They provide the baseline data and provide much or all
also serve as an excellent example of how regis- of the follow-up data, including some of the safety
try data was used to argue for increased funding monitoring data. This “efficient study design”
of KRT as their country’s national wealth greatly reduces the burden and cost of trials. Two
increased [18]. examples of registry trials are presented below.
In South America, the Latin American Dialysis In the UK, the Campath, Calcineurin inhibitor
and Transplant Registry [19] has contributed to reduction, and Chronic allograft nephropathy
the development of national registries and (3C) study randomised kidney transplant recipi-
allowed participating countries to report their ents to tacrolimus or sirolimus maintenance ther-
treatment rates and outcomes in the context of apy [22]. Researchers were able to obtain
follow-up data on graft function, patient survival, tant and common ethical concern over owner-
cancer and cause-specific mortality for one of the ship and sharing of personal data. It may be
randomisation arms by linking to routine data- useful for him to understand how the data col-
bases including Hospital Episode Statistics, the lated from all units across the country helps to
Office for National Statistics, UK Transplant and drive and maintain improvements in dialysis
the UK Renal Registry. care at his unit. He can be reassured that collat-
In Australia and New Zealand, the Better ing anonymised data from all patients receiving
Evidence for Selecting Transplant Fluids (BEST- kidney care in the country, whilst ensuring the
Fluids) trial is evaluating the effect of intravenous safety of all identifiable personal data, is central
therapy with Plasmalyte® versus 0.9% saline on to the role of the national renal registry. He may
delayed graft function following deceased donor also be interested to learn about how certain
kidney transplantation. Participants will be research studies have been delivered more effec-
enrolled, randomised and followed up using tively with the support of national renal regis-
ANZDATA, the Australia and New Zealand tries. Finally, he may like to see an example of
Dialysis and Transplant Registry [23]. the data report—which is made freely available
to clinicians and patients alike.
Practice Points
• Involving your patient in a national Questions
renal registry is central to improving
kidney care for all patients 1. What is the estimated global prevalence of
• Where there is no current national renal kidney disease?
registry—particularly in LMICs, there is A. 200 million
international support available to B. 350 million
develop one C. 500 million
D. 850 million
E. 1000 million
Answer D. The “single number” paper of Jager
Conclusions et al. estimated that the total number of peo-
ple with acute or chronic kidney disease
The importance of kidney health surveillance exceeds 850 million (Kidney Int. 2019;
systems has been recognised in the ISN’s inte- 96:1048–1050).
grated end-stage kidney disease (ESKD) strat- 2. Which is the world’s oldest renal registry?
egy [24]. Most high-income countries have a A. Australia and New Zealand Dialysis and
renal registry, but this is not yet the case for Transplant Registry (ANZDATA)
LMICs, where the impacts of kidney failure can B. European Renal Association (ERA)
be catastrophic at the human and societal level. Registry
Registry data is critical to inform the planning C. Malaysian Renal Registry
of nephrology services and to argue for more D. US Renal Data System (USRDS)
resources for comprehensive kidney care. More E. The South African Renal Registry
recently, registries are increasingly being used Answer B. The ERA Registry was the first,
in pragmatic clinical trials to reduce the costs established in 1964.
and improve the generalisability of the research 3. Which are the most important benefits of a
findings. renal registry?
Returning to the clinic, and our 54-year-old A. Informs the planning, delivery and evalu-
gentleman on haemodialysis, who wishes to ation of nephrology services
know what is happening to his data at the national B. Helps to direct the care of individual
renal registry. His question highlights an impor- patients
C. Collects comprehensive information for C. Developing a database and an online data

research projects capture system
D. Tracks expenditure related to kidney D. Drafting policies for data access and
replacement therapy publications
E. Compares the performance of nephrolo- E. Securing funding for the registry
gists and treatment centres Answer: A. All the above are impor-
Answer A: Providing critical information for tant, but identifying stakeholders, assem-
the planning, delivery and evaluation of bling the team and clarifying the purpose,
nephrology services is the main purpose. A scope and outputs are the priorities at the
registry will not typically help to direct an start.
individual patient’s care, although including 6. Should registries strive to access multiple
an individual patient’s data may help inform data sources?
the care of future patients with a similar A. Only data submitted by the patient’s doc-
condition. Some well-established registries tor should be used
do report centre-based data, but this is not B. Only data submitted by the patient’s
common and could lead to reduced partici- treatment centre should be used
pation by nephrologists and treatment cen- C. Only data submitted by the patient’s doc-
tres when establishing a new registry. tor or treatment centre should be used
4. What is the likely reason for the low preva- D. Yes, using multiple sources would
lence of patients on kidney replacement ther- improve data completeness and quality
apy in South Africa (186 pmp in 2018)? E. Patients should be consulted and data
A. The burden of kidney disease is low collection adapted accordingly
B. Data capture is incomplete and there is Answer D. The strength of a registry lies in cap-
substantial under-reporting turing accurate data on all (or almost all)
C. The South African registry does not patients. Accessing multiple data sources
include patients with a kidney transplant would improve data completeness and
D. The South African registry does not quality.
include patients treated in private treat- 7. What should be included in the dataset col-
ment centres lected by new registries?
E. Access to kidney replacement therapy is A. A minimum dataset: demographics, pri-
low because of limited resources mary disease, treatment start/end and
Answer E: Access to KRT in the poorly modality
resourced public healthcare sector is the B. Basic data plus data on treatment aspects
main reason; this sector provides care for such as dialysis adequacy, vascular
85% of the population and, unfortunately, access, etc.
there has been no real increase in access to C. Basic data plus data on treatment aspects,
KRT over the past two decades. The South laboratory tests and hospitalisations
African Renal Registry has country-wide D. Data as above, plus data patient reported
coverage, in both public and private health- outcomes, such as quality of life
care sectors, and includes all modalities of E. Comprehensive data to facilitate research
KRT. projects
5. Which are the important initial steps when Answer A. New registries are advised to keep
setting up a renal registry? the dataset to the minimum to reduce the
A. Identifying stakeholders, assembling the administrative burden and increase compli-
team and clarifying the purpose, scope ance with data submission, especially where
and outputs this is not mandatory. Once regular data sub-
B. Finding cases, collecting data and ensur- mission has been established, additional
ing data quality information can be requested.
8. Please indicate whether each of the follow- gramme, which saw a marked increase in
ing statements about renal registries are true access to peritoneal dialysis as the initial
or false. modality of treatment.
A. Renal registries can aid efforts to pre- C. Data from the Malaysian Renal Registry
vent, detect and treat the earlier stages was used to successfully argue for
of CKD by identifying the most impor- increased funding of KRT as their coun-
tant causes of kidney failure in each try’s national wealth increased
country D. The 3C study randomised kidney trans-
B. Renal registry data allows the nephrolo- plant recipients to tacrolimus or siroli-
gist to predict the exact cause of death in mus maintenance therapy, with follow-up
a patient who has been on kidney replace- data on graft function, patient survival,
ment therapy for four years and mortality obtained by linking to rou-
C. Registry data can highlight disparities in tine databases including the UK Renal
the provision of KRT services within and Registry
between countries E. In South Africa, the first report of the re-
D. A patient can request to have his/her established South African Renal Registry
identifiable data deleted from the revealed a markedly uneven distribution
registry of KRT across provinces and large differ-
E. Renal registries can identify sub-groups ences in prevalence rates between the
with reduced access to treatment or poor resource-constrained public healthcare
outcomes and monitor the adoption and sector and the well-resourced private sec-
impact of evidence-based interventions tor (73 vs. 620 pmp).
A. True Answers: A–E are all True.
B. False - Registry data reports on groups of 10. Which aspects of a registry facilitate com-
patients and can generate the probabili- parisons of aggregate data?
ties of outcomes of interest, but these A. Careful capturing of data from the notes
cannot be expected to always apply in of the treating doctor
individual patients B. Avoiding methods other than online data
C. True capture
D. True – If possible, suggest that your C. Obtaining ethical approval for data
patient considers the option of having sharing
only the identifiable information deleted, D. Ensuring that duplicate entries are avoided
or replaced by a code, so that all the infor- E. A data dictionary which uses well-
mation is not lost. Explain the importance established definitions and coding
of including everyone’s information and systems
the measures being taken to keep it safe. Answers: E. The data dictionary describes the
E. True elements to be collected and specifies the
9. Please indicate (True/False) whether each of data type (categorical, ordinal, numerical),
the following are real-life examples of ques- precision (number of decimal points), range
tions answered by a renal registry. of acceptable values, etc. Definitions should
A. Establishing the Tunisian dialysis regis- conform to those used by well-established
try led to an increase in the number of registries to facilitate comparisons and to
nephrologists, development of a new allow the aggregation of data. For example,
transplantation programme, new dialysis the coding of the primary kidney disease
units, and a kidney disease prevention should use an established system such as the
programme ERA Registry coding scheme.
B. The Thailand Renal Replacement 11. The majority of existing renal registries
Therapy Registry was instrumental in report on which group of patients
building the case for the “PD First” pro- predominantly?
A. Patients with a genetic kidney disease B. Variations in the data collection

B. Patients with ESKD treated with dialysis C. Different patterns of disease prevalence
or transplantation D. Many registries do not collect data on
C. All patients with CKD of any cause transplants
D. Patients with AKI E. The exclusion of adults on peritoneal
E. Only those patients with an unknown dialysis from most registries
aetiology of their kidney disease Answer: A. Differing access to dialysis and
Answer: B. Patients with ESKD treated with transplantation
dialysis or transplantation A. Differing access to dialysis and trans-
A. Patients with a genetic kidney disease— plantation—correct—in LMICs in par-
incorrect—all causes of kidney disease ticular, access to dialysis and
are considered, not solely those with a transplantation may be limited, thus giv-
genetic kidney disease ing an artificially low reported
B. Patients with ESKD treated with dialysis prevalence.
or transplantation—correct—Most reg- B. Variations in the data collection pro-
istries report on patients with kidney cess—incorrect—The extremely wide
failure who are treated with dialysis or variation in reported prevalence is mainly
transplantation—there are few coun- a reflection of differing access to dialysis
tries with registries for CKD or AKI and transplantation
C. All patients with CKD of any cause— C. Different patterns of disease preva-
incorrect—Most registries report on lence—incorrect—while the burden of
patients with kidney failure who are kidney disease will indeed vary globally,
treated with dialysis or transplantation— the access to dialysis and transplantation
there are few countries with registries for amongst patients with ESKD makes a
CKD or AKI more significant contribution.
D. Patients with AKI—incorrect—Most D. The majority of registries do not collect
registries report on patients with kidney data on transplants—incorrect—
failure who are treated with dialysis or According to SharE-RR, 74% of regis-
transplantation—there are few countries tries do collect transplant data.
with registries for CKD or AKI E. The exclusion of adults on peritoneal
E. Only those patients with an unknown dialysis from most registries—incor-
aetiology of their kidney disease—incorrect—According to SharE-RR, 92% of
rect, the registry will include patients registries collect data on peritoneal
with both known and unknown aetiolo- dialysis.
gies of their kidney disease.
12. It is recognised that the reported prevalence Test your learning and check your under-
of kidney replacement therapy varies widely standing of this book’s contents: use the
between countries. Which of these factors is “Springer Nature Flashcards” app to access
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A. Differing access to dialysis and 1.
transplantation
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2. Alberts C, Drukker W. Report on regular dialysis in
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4. Teraoka S, Toma H, Nihei H, Ota K, Babazono T, 17. Dhanakijcharoen P, Sirivongs D, Aruyapitipan S,
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therapy in Japan. Am J Kidney Dis. 1995;25:151–64. icy in Thailand: three-years experiences (2008-2011).
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kidney disease in the United States. Bethesda, MD: 18. Lim TO, Goh A, Lim YN, Morad Z. Use of renal
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7. Davids MR, Jardine T, Marais N, Jacobs JC, Sebastian 20. Jardine T, Wong E, Steenkamp R, Caskey FJ, Davids
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Index
A pre-renal, renal, and post-renal causes, 53

Acidosis, 527 Acute rejection, 446, 487
Active surveillance, 336–337 Acute respiratory distress syndrome (ARDS), 479
Acute coronary syndrome (ACS) Acute symptoms, 439
CI-AKI, 176 Adolescent, 507–509, 515
clinical presentation, 174 Adrenalectomy, 336
investigation and diagnosis, 174, 175 Adult polycystic kidney disease (APKD), 490, 491
NSTEMI, 174 Advance care planning (ACP), 532
overview, 173 Advanced glycation end-products (AGEs), 388
STEMI, 174 Advocacy, 564
Acute interstitial nephritis, 30 Adynamic bone disease, 144
Acute intradialysis haemolysis, 373 Alemtuzumab, 452
Acute kidney injury (AKI), 3, 9, 70–72, 229, 230 Alport syndrome, 270, 435, 453
clinical presentation, 55 Amino acid solution, 391
diagnostic criteria, 51–53, 68, 69 Amyloidosis secondary to lepromatous leprosy, 263
differential diagnosis, 59 Anaemia, 363
follow-up, 67 causes, 95
incidence, 53 definition, 94
intercurrent/acute illness, 53, 55 diabetes mellitus, 95
investigations, 57, 58 haemoglobin-based regime, 98, 99
KRT HIF, 107, 108
discontinuation of, 66 intravenous (IV) iron
indications, 64, 65 adverse effects, 101
modality for, 65, 66 blood transfusions, 106, 107
palliative care, 66, 67 ESA therapy, 103–106
management strategies, 59 infection risk, 102
acidosis, 62 oxidative stress, 102
hyperkalaemia, 62, 63 preparation, 100
hypervolaemia, 62, 64 TREAT study, 102–104
hypovolaemia, 60 management, 108–112
parenchymal causes, 62 pathophysiology, 95
sepsis, 60 patient history, 93
symptomatic uraemia, 64 prevalence, 94, 95
toxins, 60, 61 prognosis, 98
urinary tract obstruction, 61, 62 symptoms, 97
medications, 69 tests of, 98
outcomes, 67 treatment effects, 97
patient history, 51 treatment options, 98, 99
pregnancy, 496–498 weight-based single dose infusion/weight, 98, 99
© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature 575
Switzerland AG 2023
https://doi.org/10.1007/978-3-031-09131-5
576 Index
ANCA associated vasculitis (AAV) PSGN, 243

clinical presentation, 214 reflux nephropathy, 238
defects, 214 sepsis, 243
differential diagnosis, 215 tuberculosis (see Tuberculosis (TB))
incidence, 213 UTIs (see Urinary tract infections (UTIs))
investigations, 214, 215 Bacterial infection-related glomerulonephritis (B-IRGN),
management, 215, 216 243, 244
patient history, 213 Bacterial infections
Anemia, 527 leprosy, 241
Angiomyolipomas (AMLs), 320, 329 reflux nephropathy, 239
Angiotensin-converting enzyme inhibitors (ACEi), 122, Bardet-Biedl syndrome, 278
123 Basiliximab, 452
Anorexia, 529 Bence Jones proteins, 40
Antenatal care, 492 Bilateral leg oedema, 194
Antibody mediated rejection (AMR), 446 Bioimpedance techniques, 379
Anti-cholinergic drugs, 530 BK virus, 260, 445, 475, 476
Anti-phospholipase A2 receptor, 30 Blood pressure, 87, 126–128, 527
Antiphospholipid (APL) antibody syndrome (APS), 219 in dialysis patients, 124, 125
Aortic stenosis, 186–188 exercise, 121
Appropriate Blood Pressure Control in Diabetes (ABCD) healthier diet, barriers, 121
trial, 118 lifestyle measurement, 119–121
Arrythmias measurements, 115, 116
atrial fibrillation mineralocorticoid receptor antagonist, 123, 124
anticoagulation, 179, 181 patient history, 115
bleeding complications, 179 in peritoneal dialysis patients, 125
calculation of, 180 pharmacological treatment
rate control, 180, 182 diabetes, 122, 123
rhythm control, 181, 182 non-diabetics, 122
risk factors, 181 patient monitoring, 122, 123
valvular heart disease in transplant patients, 126
assessment, 185 treatment
MDT approach, 184 cardiovascular mortality, 118, 119
pathophysiology, 185 intensive treatment target, 119
prevalence, 184 outcomes, 116
prevention, 185, 186 progression, 117, 118
ventricular arrhythmias, 181, 183, 184 Breastfeeding, 493
Arterial pressure, 351 Breathlessness, 529
ASO titre, 262 Button-hole cannulation strategy, 362
Atrial fibrillation (AF), 193
anticoagulation, 179, 181
bleeding complications, 179 C
calculation of, 180 Calcimimetics, 139, 140
rate control, 180, 182 Calcineurin inhibitor (CNI), 455
rhythm control, 181, 182 Calcium and phosphate, 527
risk factors, 181 Canadian guidelines, 427
Atypical haemolytic uremic syndrome (aHUS), 292, 501 Cancer, 44
Automated peritoneal dialysis (APD), 386, 406 Cardiac arrhythmias, 367
Autosomal dominant polycystic kidney disease Cardiovascular disease, 422–424
(ADPKD), 270, 281, 424 Caregivers, 513
Autosomal dominant tubulointerstitial kidney disease Catheter-related bloodstream infection (CRBSI), 375
(ADTKD), 285 Catheter-related infection, 407, 408
Autosomal recessive polycystic kidney disease Cerebellar and spinal haemangioblastomas, 321
(ARPKD), 283 Cerebrovascular disease, 423–424
Cervical cerclage, 503
Cholesterol, 527
B Chromosomal microarray (CMA), 271
Bacterial infection Chronic allograft failure, 483, 484
B-IRGN, 243, 244 Chronic inflammatory bowel disease, 30, 31
DIN, 243–245 Chronic intradialysis haemolysis, 373
leprosy, 241, 242 Chronic kidney disease (CKD), 3, 269, 383, 490, 509,
leptospirosis, 242 534–536
Index 577
ACS (see Acute coronary syndrome (ACS)) Congenital abnormalities of Kidney and Urinary Tract
aortic stenosis, 186–188 (CAKUT), 311, 318
arrythmias (see Arrythmias) Conservative care, 521
blood pressure (see Blood pressure) advance care planning, 533
CAD (see Coronary artery disease (CAD)) chronic kidney disease, 527
causes, 86 end-stage kidney disease, 522
classification, 77, 78 excellent symptom control, 528
definition, 75 key elements, 522, 523
diabetes (see Diabetes) network of Care, 532
diagnosis, 75, 82–84 palliative care team, 533
diagnostic criteria, 52, 53 shared decision making, 523, 526, 527
epidemiology, 76, 85 social work, 533
investigations, 86, 87 variations, 522
management, 89–91 wider needs assessments, 532
complications, 88 Continuous ambulatory peritoneal dialysis (CAPD), 386
drug dosing and adjustments, 88 Contrast induced AKI (CI-AKI), 176
KRT, 88, 89 Control of Hypertension in Pregnancy Study (CHIPS),
of anaemia (see Anaemia) 493
progression, 87, 88 Coronary artery bypass grafting (CABG), 172, 173
reversible causes, 87 Coronary artery disease (CAD), 194, 436
SGLT2 inhibitors, 88 clinical presentation, 168
mineral and bone disorder in (see Chronic kidney factors, 168
disease-mineral bone disorder (CKD-MBD)) investigations, 168–171
mitral valve regurgitation (see Mitral valve management
regurgitation) clinical trials, 171, 172
pathophysiology, 76, 77 lipid modification, 171–173
patient history, 75, 85 OMT, 171
prevention, 82 revascularisation, 172, 173
progression and complications, 78–81 patient history, 167
Chronic kidney disease-mineral bone disorder (CKD- COVID-19, 260
MBD), 131, 142–144 Cryoablation, 337
clinical presentation, 134 Cryoglobulinaemia, 219, 220
epidemiology, 132 Cryotherapy, 337
investigations, 134, 135 Cystic kidney disease, 279
management Cystinosis, 304
active vitamin D, 137, 139 Cystinuria, 309
calcimimetics, 139, 140 Cytomegalovirus (CMV), 247, 248, 260, 445, 473, 474
calcium, 141 Cytoreductive nephrectomy (CN), 336
magnesium, 141
native vitamin D, 137
overview, 135 D
parathyroidectomy, 140 Delayed graft function (DGF), 483
phosphate binders, 136–139 Dengue fever, 262
phosphate restriction, 136 Dengue haemorrhagic fever (DHF), 245
mechanisms of action, 141 Dengue shock syndrome (DSS), 245
pathogenesis of Dengue virus (DV) infection, 245
mineral metabolism abnormalities, 132, 133 Depression, 503
vascular calcification, 133, 134, 141 Diabetes, 75, 76, 79, 82, 118, 121, 150, 163–165
patient history, 131 clinical presentation, 149
Chronic pyelonephritis, 238, 239 differential diagnosis, 151
Chronic tubulo-interstitial nephritis (TIN), 238 investigations for, 149, 150
Cirrhosis, 403 management
CKD of unknown aetiology (CKDu), 76 augmenting therapy, 155
CKD-Epidemiology Collaboration (CKD-EPI) formulae, DPP-4 inhibitors, 157, 158
15 first-line therapy, 153–155
CKD-modified diet in renal disease (CKD-MDRD), 15 GLP-1 RAs, 155, 157
COL4A3 mutation, 319 glycaemic control, 151
Colonic villous adenoma, 31 hypertension, 159–161
Complement-dependent cytotoxicity (CDC), 437 lifestyle changes, 152, 153
Complement-mediated MPGN, 206, 207 meglitinides, 158, 159
Comprehensive geriatric assessment (CGA), 532 post-transplant diabetes mellitus, 159
578 Index
Diabetes (Cont.) pathology, 202

sulfonylurea, 158 patient history, 201
thiazolidinediones, 158 treatment, 201–203
patient history, 147 Full blood count (FBC), 497
prevalence, 148 Fungal infection, 259, 403
Diabetes mellitus, 436 Fungal peritonitis, 418
Diabetic control, 527
Diabetic kidney disease (DKD), see Diabetes
Diabetic nephropathy, 46, 48 G
See also Diabetes Genetic kidney diseases
Dialyser membranes, 353–354 CAKUT, 311, 318
Dialyser reuse, 357 classification of
Dialysis, 102, 105, 349, 563 ARPKD, 283
Dialysis access ischemic steal syndrome (DAISS), 368 cystic kidney disease, 279
Dialysis adequacy, 394 glomerular diseases, 290, 292, 316
Dialysis dementia, 371 interstitial kidney disease, 284
Dialysis pericarditis, 368 monogenic kidney diseases, 278
Dialysis-associated pruritus, 375 tumourous kidney diseases, 288, 316
Dialysis-related headache (DRH), 370 cystinosis, 304
Dialysis-related muscle cramps, 371–372 cystinuria, 309
Dialyzer clearance, 350 genetic testing
Diazepam, 370 benefits & risks of, 273
Dietary Approaches to Stop Hypertension (DASH) diet, genetic counselling, 274
120 hereditary nephropathy, 275
Dipeptidyl peptidase-4 (DPP-4) inhibitors, 157, 158 types of, 275
Dobutamine stress echocardiogram, 190 Gitelman syndrome, 302–303
Donor specific antibodies (DSA), 456 hereditary systemic amyloidosis, 318
DPP4 inhibitors (DPP4i), 155 kidney tubulopathies, 296, 317
Drug-induced nephrotoxicity (DIN), 243–245 monogenic (single-gene) disorders, 271–273
nephrolithiasis, 305, 307
primary hyperoxaluria type 1, 310
E Genetic testing, 319
Ebola infection, 245, 247 Gerota’s fascia, 335
Electrolyte abnormalities, 544 Gestational diabetes mellitus (GDM), 495, 504
Encapsulating peritoneal sclerosis (EPS), 400, 416, 417, Gitelman syndrome (GS), 302–303
419 Glomerular disease, 44, 290, 292, 316
End stage kidney disease (ESKD), 229, 230, 241, 386, AAV (see ANCA associated vasculitis)
405, 436, 455, 522, 523, 563 APS, 219
End-stage renal disease (ESRD), 421 cryoglobulinaemia, 219, 220
Epithelial-to-mesenchymal transition (EMT), 390 lupus nephritis (see Lupus nephritis (LN))
Epstein–Barr Virus (EBV), 474 protein deposition disease, 220–222
Erythropoietin (EPO), 108 TMAs, 222–224
Erythropoietin stimulating agents (ESA) therapy, Glomerular filtration rate (eGFR), 15, 489
103–106, 495 Glomerular proteinuria, 36, 39
Estimated albumin excretion rate (eAER), 38 Glomerulonephritis, 209–211
Estimating the protein excretion rate (ePER), 38 clinical syndromes, 199
Exercise, 121 focal segmental glomerulosclerosis
Exit site scoring system, 407 aetiopathogenesis, 201
Extracorporeal blood circuit (ECC), 350–352 clinical presentation, 201
epidemiology, 201
laboratory findings, 201
F pathology, 202
Fabry disease (FD), 276, 295 patient history, 201
Fibrous crescent, 31 treatment, 201–203
Flank pain, 331 IgAN, 205, 206
Fluid management, 500 minimal change disease
Focal segmental glomerulosclerosis (FSGS), 261, 448 aetiopathogenesis, 200
aetiopathogenesis, 201 clinical presentation, 200
clinical presentation, 201 epidemiology, 200
epidemiology, 201 laboratory findings, 200
laboratory findings, 201 pathology, 201
Index 579
patient history, 199 haematologic complications, 374

treatment, 200, 201 haemorrhage, 373
MPGN, 206, 207 intra-dialytic haemolysis, 372–373
PMN, 203–205 thrombocytopaenia, 374
PSGN, 207, 208 hearing loss, 376–377
GLP-1 receptor agonists (GLP-1 RAs), 155, 157 high flux hemodialysis, 349
Glucose-based solutions, 388–389 home hemodialysis, 358
Glycaemic control, 151 infections in patients, 375
Gram negative peritonitis, 418 Iso UF mode, 356
membranes, 353–354
nurological complications
H dialysis dementia, 371
Haematuria, 3, 6, 7, 331 dialysis-related muscle cramps, 371–372
cancer, 44 DRH, 370
causes of, 43, 44 seizures, 369
cystoscopy, 43, 44 optimizing dialysis prescription, 356
decision algorithm, 41, 42 personalized dialysis, 360
dipstick testing of urine, 41 post-dialysis fatigue, 375
glomerular disease, 44 preparation & monitoring, 352
history, 41 priapism, 375–376
imaging investigations, 43 reuse, 357
macroscopic, 44, 46, 48 single HD treatment, 356
microscopic, 44 SNHD, 357
schistosoma haematobium infection, 44, 45 standard prescription, 355
sickle cell disease, 45 techniques, 354
urinary sediment, 43 treatment, 351
Haemodiafiltration, 362 UF and RRF, 356
Haemodialysis, 431 ultrafiltration, 350
Haemodialysis-associated seizures, 370 ultrafiltration control systems, 352
Haemoglobinuria, 40 water treatment systems, 352–353
Haemorrhage, 373 Hemodialysis associated heparin-induced
Hantavirus (HV) infection, 245 thrombocytopaenia (HIT), 374
Hearing loss, 376–377 Hemodialysis techniques, 354
Heart failure, 193, 194 Heparin-induced thrombocytopenia (HIT), 377
classification, 176 Hepatitis A virus (HAV), 248
diagnosis, 176 Hepatitis B virus (HBV), 248, 249, 426
diuretic therapy, 179 Hepatitis C virus (HCV), 249, 250, 375, 426
long term outcomes, 176–178 Hepatitis E virus (HEV), 248
management, 176 Hepcidin, 95, 108
HELLP syndrome, 500 Hereditary kidney tumours, 328
Hematologic disorders, 426–427 Hereditary systemic amyloidosis, 318
Hematuria, 430 Hernias, 414, 415
Hemodialysis High potassium, 527
acute heparin free, 355–356 Home hemodialysis, 358
anticoagulation, 355–356 Human immunodeficiency virus (HIV), 252, 425–426
bypass and recirculation mode, 357 Hydrochlorothiazide, 560
cardiovascular complications Hydrothorax, 416
cardiac arrhythmias, 367 Hypercalcaemia, 503
DAISS, 368 Hyperkalaemia, 62, 63, 195
dialysis pericarditis, 368 Hyperkalemia, 548, 552
intradialytic hypertension, 366–367 Hypermagnesemia, 559
intradialytic hypotension, 364, 365 Hypernatremia
carpal tunnel syndrome, 349 causes, 542
clearance, 350 diagnosis, 542
convection, 350 treatment, 544
defined, 349 Hyperphosphatemia, 135
dialysis-associated pruritus, 375 Hypertension, 436
diffusion, 350 diabetes, 159–161
ECC, 351 See also Blood pressure
governance and quality assurance, 358–360 Hypertension optimal treatment (HOT), 118
580 Index
Hypervolaemia, 62, 64 causes, 329–330

Hypokalemia, 393, 544, 547, 548 clinical presentation, 331
Hyponatremia, 539, 541 coronal contrast-enhanced CT scans, 327
Hypovolaemia, 60 cryoablation, 337
Hypoxia-inducible factors (HIFs), 107, 108, 330 epidemiology, 329–330
Hypoxia-inducible-factor prolyl hydroxylase (HIF-PH) follow up, 340–341
inhibitors, 141 genetic mutations, 330
management of, 337
metastatic kidney cancer, 338
I non-RCC renal tumour subtypes, 328–329
Icodextrin, 389–390 pathophysiological mechanisms, 330
IgA nephropathy (IgAN), 46, 48, 205, 206 prognosis, 340
Immune-complex-mediated MPGN (IC-MPGN), 206 proposed surveillance schedule, 340
Immunosuppression, 455 RCC, 328
Implantable loop recorder (ILR) devices, 183 renal tumour biopsy, 333
Infection, 435 RFA, 337
International Society for Peritoneal Dialysis (ISPD), 406 risk factors, 329
Interstitial kidney disease, 284 stage grouping, 335
Intra-dialytic haemolysis, 372–373 staging of, 335
Intradialytic hypertension, 366–367 surgery, 335, 336
Intradialytic hypotension (IDH), 124, 364, 365 systemic therapies, 339, 340
Investigations, 32, 33 TNM classification, 335
features, 29 upper pole lesion, 327
haematology tests, 12, 14 WHO grading, 335
histopathology Kidney disease
electron microscopes, 25, 27 causes, 4
immunohistochemical techniques, 25, 27 clinical features, 3
kidney biopsy, 24, 25, 29, 30 definition, 3
light microscope, 25, 26 diagnosis, 9
tissue examination and interpretation, 25, 28 haematuria, 6, 7
immunological and virological tests, 12, 14–15 kidney replacement therapy, 7, 8
patient history, 11, 31 management, 9
radiological imaging patient approach, 5–6
abdominal x-ray, 20 patient history, 1
chest radiograph, 19, 20 patient presentation, 3
computed tomography, 21, 22 symptoms and signs, 1–3
magnetic resonance imaging, 22 syndromes, 3
nephrogenic systemic fibrosis, 23 Kidney failure, 563, 564
renal doppler ultrasound scans, 21 Kidney health surveillance systems, 564, 569
renal scintigraphy, 23 Kidney replacement therapy (KRT), 88, 89, 270, 363,
ultrasound, 20, 21 405, 495, 521
serum biochemistry, 12–13, 31 discontinuation of, 66
GFR, 15 indications, 64, 65
urea and creatinine, 13 modality for, 65, 66
urea and electrolytes, 13 palliative care, 66, 67
urine tests Kidney stones, 3
appearance, 16 Kidney transplantation, 435, 495
dipstick analysis, 17, 19 acute and chronic rejection, 480, 481
urine-based investigations, 18–19 anti rejection therapies, 447
Iron deficiency anaemia (IDA), 99 antihypertensive agents, 443
Ischaemic heart disease, 191, 192 antimicrobial prophylaxis, 443
Isolated ultrafiltration (Iso UF), 356–357 antimicrobials, 444
Isopropyl alcohol, 559 BK virus, 475
blood chemistry, 441
calcineurin inhibitor nephrotoxicity, 483
K calcineurin inhibitors, 444
Karnofsky Performance Status Score, 342 cancer, 484
Kidney allograft, 450 cancer screening, 422, 450
Kidney biopsy, 498 cardiovascular risk reduction, 449
Kidney cancer complementary optional testing, 423
active surveillance, 336, 337 complete blood count, 441
Bosniak classification, 332, 333 contraindications, 422
Index 581
COVID-19, 479 Leprosy, 241, 242

delayed graft function, 483 Leptospirosis, 242
diabetes mellitus, 443 Liddle’s syndrome, 557
difficult-to-care-for, 451 Liver function test, 497
discharge and education, 438 Lupus nephritis (LN), 490
ESRD, 421 clinical presentation, 217
fungal infections, 478, 479 defects, 217
graft survival, 455 differential diagnosis, 218
high drain output post kidney transplant, 465–467 incidence, 217
hydronephrosis, 467, 468 investigations, 217, 218
imaging abnormalities, 442 management, 218, 219
laboratory abnormalities, 440 patient history, 217
latent mycobacterium tuberculosis, 477 Lymph node dissection (LND), 336
living donor Lymphocele, 487
contraindications for, 429
donation evaluation, 427
follow-up, 428 M
hematuria, 430 Magnesium sulphate, 499
older donors, 431 Malaria, 253–256, 261
optional testing, 429 Malignancy, 424, 425, 435
required evaluations, 428 MDT approach, 184
risk of donation, 429–430 Membranoproliferative glomerulonephritis (MPGN),
risk of gout, 430 206, 207
testing, 428 Memorial Sloan Kettering Cancer Center (MSKCC)
localized infections, 445 Prognostic Model, 338
long term continuum, 451 Metabolic acidosis, 554–556
medical complications, 473 Metabolic alkalosis, 552, 553
mycobacterium tuberculosis, 476, 478 Metastatic Renal Cell Carcinoma Database Consortium
oliguria post kidney transplant, 471 (IMDC) Criteria, 338
Pneumocystis jiroveccii, 476 Microalbuminuria, 38
pneumonia, 444 Middle molecule toxicity, 361
post-discharge care, 438, 439 Minimal change disease (MCD)
post-transplant diabetes, 480 aetiopathogenesis, 200
pre-transplant evaluation, 423 clinical presentation, 200
recipient evaluation team, 421–422 epidemiology, 200
referred for, 421 laboratory findings, 200
renal transplant recipient pathology, 201
ages, 425 patient history, 199
cardiovascular disease, 422–424 treatment, 200, 201
cerebrovascular disease, 423–424 Minimal-change disease, 46, 48
hepatitis B, 426 Mitral valve regurgitation
hepatitis C, 426 classification, 187
HIV, 425–426 investigation, 187
malignancy, 424, 425 management, 187–189
obesity, 425 mechanical valve prostheses, 189
peripheral vascular disease, 424 pre-transplant patient, 189, 190
pulmonary disorder, 426 Modes of inheritance (MOI), 272
tuberculosis, 426 Monogenic (single-gene) disorders, 271–273
surgical complications, 437, 457–465 Monogenic kidney diseases, 278
systemic infections, 445 Monogenic X-linked nephropathy, 276
transplant recipient testing, 422 Mycobacterium tuberculosis (MTB), 476
urinary tract infections, 444 Mycophenolate mofetil (MMF), 495
urologic complications, 465 Myoglobin (Mb), 39
vaccinations, 422
vascular complications, 469, 470
Kidney tubule defects, 3 N
National Organisations of Rare Disorders (NORD), 271
Nephritic syndrome, 3
L Nephrolithiasis, 305, 307
Lactate dehydrogenase (LDH), 497 Nephron sparing, 335
Latent mycobacterium tuberculosis (LMTB), 477 Nephrotic syndrome, 3, 9, 29
582 Index
Neuropathic pain, 528 nutrition status, 393

Next-generation sequencing (NGS), 271 patient reported outcome measures, 392
No known kidney disease (NKD), 52, 53 peritoneal equilibration test, 397
Nociceptive pain, 528 peritoneal infections or inflammation, 383
Non-ST elevation myocardial infarction (NSTEMI), 174 PEW, 393
Normalized protein nitrogen appearance (nPNA), prescription, 391
395–396 prevention of infection, 406
prognosis, 411
RCTs, 396
O RKF, 393–395
Obstructive sleep apnoea, 181 treatment of infections
Oliguria post kidney transplant, 470, 472 catheter-related infection, 408
Optimal medical therapy (OMT), 171 peritonitis, 409, 410
Optional testing, 429 UFF, 400, 401
Orthostatic proteinuria, 36, 47, 49 ultrafiltration, 398
Overflow proteinuria, 36, 39, 40 urgent start, 385
Oxalosis, 436 volume status, 393
Oxidative stress, 102 Peritoneal equilibration test (PET), 396, 415
Peritoneal membrane failure (PMF), 389
Peritoneal solute transport (PSTR), 389
P Peritonitis, 407, 409, 410
Palpable abdominal mass, 331 Peritubular capillaries (PTC), 481
Papillary adenoma, 328 Persistent isolated proteinuria, 38
Paraneoplastic syndromes, 331 Personalized dialysis, 360
Paraproteinemia, 436 PKD1 mutation, 320
Parathyroidectomy, 140 Placental growth factor (PlGF), 494
Parvovirus B (PVB) infection, 247 Pneumocystis jiroveccii (carinii), 476
Patiromer, 559 Polyoma virus nephropathy (PVN), 247
PD modality, 384 Post-dialysis fatigue, 375
Percutaneous coronary intervention (PCI), 172, 173 Post infectious glomerulonephritis, 262
Peripheral vascular disease, 424 Postpartum haemorrhage (PPH), 501, 502
Peritoneal dialysis (PD), 125 Post-renal proteinuria, 36
adjusting PD prescription, 398 Post streptococcal glomerulonephritis (PSGN), 207, 208,
amino acid solution, 391 243
care delivery, 391–393 Post‐transplant lymphoproliferative disease
catheter placement, 385 (PTLD), 474
clinical outcomes of, 391 Potassium buffering, 548
diagnosis of infection Pre-eclampsia, 489, 498, 499
catheter-related infections, 407 Pregnancy, 493, 495
exit site scoring system, 407 Preimplantation genetic diagnosis (PGD), 274
peritonitis, 407 Priapism, 375–376
presentations of, 407 Primary hyperoxaluria type 1, 310
end-stage kidney disease, 386 Primary kidney tubulopathies, 296, 317
fluid overload, 399 Primary membranous nephropathy (PMN), 203–205
glucose-based Solutions, 388–389 Primary percutaneous coronary intervention (PPCI), 174
high transporters, 398–399 Programmed cell death protein 1 (PD-1) receptor, 330
icodextrin, 389–390 Propoxyphene, 378
infective complications, 406 Protein deposition disease, 220–222
kidney failure patients, 384 Protein-energy wasting (PEW), 393
low transporters, 399 Proteinuria, 47, 49
modalities, 386–387 definition, 36, 37
modality, 384 glomerular barrier, 35, 36
neutral pH low-GDP solutions, 390 management, 40, 41
non-infective complications patient history, 35
catheter obstruction, 413, 414 prognosis, 41
EPS, 416, 417 protein excretion
hernias, 414, 415 glomerular proteinuria, 39
hydrothorax, 416 guidelines, 37
laparoscopic techniques, 412–413 isolated, asymptomatic proteinuria, 38
leaks, 415, 416 microalbuminuria, 38
nPNA, 395 overflow proteinuria, 39, 40
Index 583
spot urine measurements, 38 Thrombotic microangiopathy, 448, 452

timed urine collections, 37, 38 Thrombotic thrombocytopenic purpura (TTP), 497, 501
tubular proteinuria, 39 Thymoglobulin, 452
urine dipstick test, 37 Transcatheter aortic valve replacement (TAVI), 186–187
variable chromogenicity, 37 Transient proteinuria, 38
tubular reabsorption and secretion, 36 Transitional care, 507, 508
Protozoal and parasitic infection Transmembrane pressure (TMP), 350
malaria, 253–256 Transplantation, 563, 565
schistosomiasis, 256–259 Travelers, 450
Pulmonary disorder, 426 Tuberculosis (TB), 426
end-stage kidney disease, 241
incidence, 235–236, 239, 240
R interstitial nephritis, 241
Radiofrequency ablation (RFA), 337–338 UGTB, 240, 241
Randomized controlled trial (RCT), 135 Tuberculous interstitial nephritis, 241
Reflux nephropathy, 238, 239 Tubular proteinuria, 36, 39
Registries, 563, 564, 566, 568, 569 Tumourous kidney diseases, 288, 316
Rejection, 435 Type 1 diabetes (T1DM), 159–161
Renal artery stenosis, 30 Type 2 diabetes (T2DM), 161, 192, 193
Renal cell carcinoma (RCC), 328
Renal cysts, 333
Renal medullary carcinoma, 328 U
Renal oncocytoma, 329 UK Prospective diabetes study (UK-PDS), 118
Renal transplant, 193, 194 Ultrafiltration (UF), 356, 361
Renal tumour biopsy, 333 Ultrafiltration failure (UFF), 400–402, 416
Renin-angiotension-aldosterone system (RAAS), 492 Uraemic pruritis, 528
Residual glomerular filtration rate (GFR), 394 Ureteric stricture, 488
Residual kidney function (RKF), 393–394 Urinary tract abnormalities, 436
Residual renal function (RRF), 356 Urinary tract infections (UTIs), 3, 36
Resistive index (RI), 21 asymptomatic bacteriuria, 236
Restless-leg syndrome, 529 chronic tubulo-interstitial nephritis, 238
complicated UTIs, 233–234, 236
epidemiology, 231
S recurrent UTIs, 237, 238
Schistosoma haematobium infection, 44, 45 uncomplicated UTIs, 231–232, 236, 237
Schistosomiasis, 256–259, 261 urosepsis, 237
Schober test, 503 Urinary tract obstruction, 3
Secondary hyperparathyroidism, 133–135, 137 Urine albumin-to-creatinine ratio (UACR), 38
Sepsis, 60, 243 Urine protein-to-creatinine ratio (UPCR), 38
Serum amyloid P (SAP) scan, 47, 48 Uro-genital tuberculosis (UGTB), 240, 241
Severe acute respiratory syndrome coronavirus-2 Urosepsis, 237
(SARS-CoV-2), 252, 253
Sickle cell disease, 45
Single needle hemodialysis (SNHD), 357 V
Staph aureus, 378 Vaccination, 450
Statin in combination with ezetimibe, 191 Valvular heart disease (VHD)
ST elevation myocardial infarction (STEMI), 174 assessment, 185
Steroid-resistant nephrotic syndrome (SRNS), 276 MDT approach, 184
Streptococcal infection, 410 pathophysiology, 185
Stroke, 179–181, 189 prevalence, 184
Sulfonylurea, 158 prevention, 185, 186
Surgical valve replacement (SAVR), 186, 187 Varicella zoster virus (VZV) infection, 248
Synpharyngitic haematuria, 205 Vascular endothelial growth factor
Systemic lupus erythematosus (SLE), 46, 48 (VEGF), 330, 400
Venous pressures (VP), 351
Venous thrombo-embolic disease, 47, 49
T Ventricular arrhythmias, 181, 183, 184
Tamm Horsfall proteins, 47, 49 Vesico-ureteric reflux
Thrombocytopaenia, 374 (VUR), 238, 239
Thrombotic microangiopathies (TMAs), 222–224 VHL tumour suppressor gene, 330
584 Index
Viral infection W
CMV, 247, 248 Water treatment systems, 352–353
DV infection, 245
ebola infection, 245, 247
hantavirus, 245 X
hepatitis A virus, 248 X-linked Alport syndrome, 276
hepatitis B virus, 248, 249 X-linked hypophosphataemia (XLH), 301
hepatitis C virus, 249, 250
hepatitis E virus, 248
HIV, 252 Y
mechanism of injury, 245, 246 Young adult worker, 511, 515
PVB, 247 Young kidney patient, 510
PVN, 247 Young person, 507, 511
SARS-CoV-2, 252, 253
VZV, 248

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Management

Your personal SN Flashcards link is provided in one of the first chapters.

ISBN 978-3-031-09130-8 ISBN 978-3-031-09131-5 (eBook)

Oakham, UK John Feehally

Worldwide, practicing nephrologists often need rapid and easily accessible

London, UK Debasish Banerjee

1  he Approach to the Patient with Kidney Disease������������������������ 1

14 I nfections and the Kidney �������������������������������������������������������������� 229

Clinical Scenario ing 14.5 million people are estimated to require

Kidney patients present may with symptoms,

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 1

Pallor/greyish hue to Facial / periorbital

Facial malar rash (SLE)

Renal angle tenderness,

SLE – systemic lupus erythematosus; CYA – cyclosporin; Ca2+ channel blockers –

 ommon Kidney Syndromes

Aetiology of Kidney Syndromes aetiologies may present with acute or chronic

Table 1.3 Common causes of kidney syndromes

 pproach to a Patient with Kidney

Table 1.4 Approach to common kidney syndromes

Table 1.4 (continued)

Conclusions tacrolimus and mycophenolate mofetil. Her most

References analysis for the global burden of disease study 2017.

Clinical Scenario Introduction

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 11

Table 2.1 Serum biochemistry tests in kidney disease

Table 2.1 (continued)

Table 2.3 (continued) demographics has allowed the widespread

eGFR (estimated glomerular filtration rate) = mL/min/1.73 m2

Urine Tests globin, myoglobin, proteins and crystals. For

Table 2.5 Common appearances of urine

Urine appearance Significance

Orange Medications such as rifampicin,

Red Blood, rifampicin, food

Fig. 2.1 Image of urine dipstick analysis

Table 2.6 The ‘urine dipstick’/urinalysis

Urine dipstick component Significance

pH Normal urine pH is acidic. The pH can be used to investigate

Specific gravity The measure of the amount of solute dissolved in urine.

Ketones Ketonuria is associated with starvation, low carbohydrate

Table 2.7 Summary of urine-based investigations when investigating kidney disease

Table 2.7 (continued)

TTKG transtubular potassium gradient = urine potassium / urine osmolality

Radiological Imaging –– Air space opacification:

malignancy, particularly in the context of I ntravascular Contrast Studies

Fig. 2.3 Ultrasound imaging of the kidneys. A normal

Cross-sectional urinary tract imaging using com-

prevent contrast nephrotoxicity (due to lack of

Magnetic Resonance Imaging (MRI)

Magnetic resonance imaging (MRI) can be an

 uclear Medicine Imaging: Renal

Table 2.9 Comparison of different renal nuclear medicine imaging modalities

Table 2.10 Indications for renal biopsy

Indications forrenal biopsy

Table 2.11 Contraindications to renal biopsy

The kidney tissue samples are typically collected Stain Significance

Oakham, UK John Feehally

London, UK Debasish Banerjee

1 he Approach to the Patient with Kidney Disease�� 1

14 I nfections and the Kidney �� 229

ommon Kidney Syndromes

Aetiology of Kidney Syndromes aetiologies may present with acute or chronic

pproach to a Patient with Kidney

Conclusions tacrolimus and mycophenolate mofetil. Her most

Clinical Scenario Introduction

Urine Tests globin, myoglobin, proteins and crystals. For

Radiological Imaging –– Air space opacification:

malignancy, particularly in the context of I ntravascular Contrast Studies

Magnetic Resonance Imaging (MRI)

uclear Medicine Imaging: Renal

Light Microscopy (LM)

Glomerular Diseases 15.12. The diagnosis and management of atypi-

Nephrolithiasis ment of nephrolithiasis in Table 15.20; and the

ongenital Abnormalities of Kidney

Conclusions our understanding of these pathways [1].

Introduction noma (RCC) is the most common solid lesion in

Genetic Basis of Kidney Cancer development of RCC. Other genetic mutations

Clinical Presentation mass. Less than 10% of patients present with

Renal Tumour Biopsy