Renal anatomy:

The tables below show the anatomical relations of the kidneys:

Right kidney
Direct contact Layer of peritoneum in-between
Right suprarenal gland Liver
Duodenum Distal part of small intestine
Colon

Left kidney
Direct contact Layer of peritoneum in-between
Left suprarenal gland Stomach
Pancreas Spleen
Colon Distal part of small intestine

Renal physiology
 Renal blood flow is 20-25% of cardiac output
 Renal cortical blood flow > medullary blood flow (i.e. tubular cells more prone to ischaemia

Acute kidney injury: acute tubular necrosis vs. prerenal uraemia

Prerenal uraemia - kidneys hold on to sodium to preserve volume
Pre-renal uraemia Acute tubular necrosis

Urine sodium < 20 mmol/L > 30 mmol/L

Fractional sodium excretion* < 1% > 1%

Fractional urea excretion** < 35% >35%

Urine:plasma osmolality > 1.5 < 1.1

Urine:plasma urea > 10:1 < 8:1

Specific gravity > 1020 < 1010

Urine 'bland' sediment brown granular casts

Response to fluid challenge Yes No

*fractional sodium excretion = (urine sodium/plasma sodium) / (urine creatinine/plasma
creatinine) x 100

**fractional urea excretion = (urine urea /blood urea ) / (urine creatinine/plasma creatinine) x 100

1
Papillary necrosis
Causes

 chronic analgesia use

 sickle cell disease
 TB
 acute pyelonephritis
 diabetes mellitus

Features

 fever, loin pain, haematuria

 IVU - papillary necrosis with renal scarring - 'cup & spill'

Nephrotoxicity due to contrast media

Contrast media nephrotoxicity may be defined as a 25% increase in creatinine occurring within
3 days of the intravascular administration of contrast media.

Risk factors include

 known renal impairment (especially diabetic nephropathy)

 age > 70 years
 dehydration
 cardiac failure
 the use of nephrotoxic drugs such as NSAIDs

Prevention

 the evidence base currently supports the use of intravenous 0.9% sodium chloride at a
rate of 1 mL/kg/hour for 12 hours pre- and post- procedure. There is also evidence to
support the use of isotonic sodium bicarbonate
 N-acetylcysteine (usually given orally) has been shown to reduce the incidence of
contrast-nephropathy in some studies but the evidence base is not as strong as for fluid
therapy

2
SLE: renal complications
WHO classification
 class I: normal kidney
 class II: mesangial glomerulonephritis
 class III: focal (and segmental) proliferative glomerulonephritis
 class IV: diffuse proliferative glomerulonephritis
 class V: diffuse membranous glomerulonephritis
 class VI: sclerosing glomerulonephritis

Class IV (diffuse proliferative glomerulonephritis) is the most common and severe form. Renal
biopsy characteristically shows the following findings:

 glomeruli shows endothelial and mesangial proliferation, 'wire-loop' appearance

 if severe, the capillary wall may be thickened secondary to immune complex deposition
 electron microscopy shows subendothelial immune complex deposits
 granular appearance on immunofluorescence

Diffuse proliferative SLE. Proliferation of endothelial and mesangial cells. The thickening of the capillary wall
results in a 'wire-loop' appearance. Some crescents are present.

Management

 treat hypertension
 corticosteroids if clinical evidence of disease
 immunosuppressants e.g. azathiopine/cyclophosphamide

3
Rhabdomyolysis
Rhabdomyolysis will typically feature in the exam as a patient who has had a fall or prolonged
epileptic seizure and is found to have acute renal failure on admission

Features

 acute renal failure with disproportionately raised creatinine

 elevated CK
 myoglobinuria
 hypocalcaemia (myoglobin binds calcium)
 elevated phosphate (released from myocytes)

Causes

 seizure
 collapse/coma (e.g. elderly patients collapses at home, found 8 hours later)
 ecstasy
 crush injury
 McArdle's syndrome
 drugs: statins

Management

 IV fluids to maintain good urine output

 urinary alkalinization is sometimes used

4
Acute vs. chronic renal failure
Best way to differentiate is renal ultrasound - most patients with CRF have bilateral small
kidneys

Exceptions

 autosomal dominant polycystic kidney disease

 diabetic nephropathy
 amyloidosis
 HIV-associated nephropathy

Other features suggesting CRF rather than ARF

 hypocalcaemia (due to lack of vitamin D)

Chronic kidney disease: causes

Common causes of chronic kidney disease

 diabetic nephropathy
 chronic glomerulonephritis
 chronic pyelonephritis
 hypertension
 adult polycystic kidney disease

Chronic kidney disease: eGFR and classification

Serum creatinine may not provide an accurate estimate of renal function due to differences in
muscle. For this reason formulas were develop to help estimate the glomerular filtration rate
(estimated GFR or eGFR). The most commonly used formula is the Modification of Diet in Renal
Disease (MDRD) equation, which uses the following variables:

 serum creatinine
 age
 gender
 ethnicity

Factors which may affect the result

 pregnancy
 muscle mass (e.g. amputees, body-builders)
 eating red meat 12 hours prior to the sample being taken

5
CKD may be classified according to GFR:
CKD stage GFR range

1 Greater than 90 ml/min, with some sign of kidney damage on other tests (if all the kidney
tests* are normal, there is no CKD)

2 60-90 ml/min with some sign of kidney damage (if kidney tests* are normal, there is no
CKD)

3a 45-59 ml/min, a moderate reduction in kidney function

3b 30-44 ml/min, a moderate reduction in kidney function

4 15-29 ml/min, a severe reduction in kidney function

5 Less than 15 ml/min, established kidney failure - dialysis or a kidney transplant may be
needed

*i.e. normal U&Es and no proteinuria

Chronic kidney disease: anaemia
Patients with chronic kidney disease (CKD) may develop anaemia due to a variety of factors,
the most significant of which is reduced erythropoietin levels. This is usually a normochromic
normocytic anaemia and becomes apparent when the GFR is less than 35 ml/min (other causes
of anaemia should be considered if the GFR is > 60 ml/min). Anaemia in CKD predisposes to
the development of left ventricular hypertrophy - associated with a three fold increase in
mortality in renal patients

Causes of anaemia in renal failure:

 reduced erythropoietin levels - the most significant factor
 reduced erythropoiesis due to toxic effects of uraemia on bone marrow
 reduced absorption of iron
 anorexia/nausea due to uraemia
 reduced red cell survival (especially in haemodialysis)
 blood loss due to capillary fragility and poor platelet function
 stress ulceration leading to chronic blood loss

Management:
 the 2011 NICE guidelines suggest a target haemoglobin of 10 - 12 g/dl
 determination and optimisation of iron status should be carried out prior to the
administration of erythropoiesis-stimulating agents (ESA). Many patients, especially those
on haemodialysis, will require IV iron
6
  ESAs such as erythropoietin and darbepoetin should be used in those 'who are likely to
benefit in terms of quality of life and physical function'
Erythropoietin
Erythropoietin is a haematopoietic growth factor that stimulates the production of erythrocytes.
The main uses of erythropoietin are to treat the anaemia associated with chronic kidney disease
and that associated with cytotoxic therapy.

Side-effects of erythropoietin

 accelerated hypertension potentially leading to encephalopathy and seizures (blood

pressure increases in 25% of patients)
 bone aches
 flu-like symptoms
 skin rashes, urticaria
 pure red cell aplasia* (due to antibodies against erythropoietin)
 raised PCV increases risk of thrombosis (e.g. Fistula)
 iron deficiency 2nd to increased erythropoiesis
*the risk is greatly reduced with darbepoetin (Aranesp)

There are a number of reasons why patients may fail to respond to erythropoietin therapy:

 iron deficiency
 inadequate dose
 concurrent infection/inflammation
 hyperparathyroid bone disease
 aluminium toxicity

Chronic kidney disease: hypertension

The majority of patients with chronic kidney disease (CKD) will require more than two drugs to
treat hypertension. ACE inhibitors are first line and are particularly helpful in proteinuric renal
disease (e.g. diabetic nephropathy). As these drugs tend to reduce filtration pressure a small fall
in glomerular filtration pressure (GFR) and rise in creatinine can be expected. NICE suggest
that a decrease in eGFR of up to 25% or a rise in creatinine of up to 30% is acceptable,
although any rise should prompt careful monitoring and exclusion of other causes (e.g.
NSAIDs). A rise greater than this may indicate underlying renovascular disease.

Furosemide is useful as a anti-hypertensive in patients with CKD, particularly when the GFR
falls to below 45 ml/min*. It has the added benefit of lowering serum potassium. High doses are
usually required. If the patient becomes at risk of dehydration (e.g. Gastroenteritis) then
consideration should be given to temporarily stopping the drug

*the NKF K/DOQI guidelines suggest a lower cut-off of less than 30 ml/min
7
Chronic kidney disease: proteinuria
 Proteinuria is an important marker of chronic kidney disease, especially for diabetic
nephropathy.
 NICE recommend using the albumin:creatinine ratio (ACR) in preference to the
protein:creatinine ratio (PCR) when identifying patients with proteinuria as it has greater
sensitivity.
 For quantification and monitoring of proteinuria, PCR can be used as an alternative, although
ACR is recommended in diabetics. Urine reagent strips are not recommended unless they
express the result as an ACR

Approximate equivalent values

ACR (mg/mmol) PCR (mg/mmol) Urinary protein excretion (g/24 h)

30 50 0.5

70 100 1

Collecting an ACR sample

 by collecting a 'spot' sample it avoids the need to collect urine over a 24 hour period in
order to detect or quantify proteinuria
 should be a first-pass morning urine specimen
 if the initial ACR is greater than 30 mg/mmol and less than 70 mg/mmol, confirm by a
subsequent early morning sample. If the initial ACR is greater than 70 mg/mmol a repeat
sample need not be tested

Interpreting the ACR results

 in non-diabetics an ACR greater than 30 mg/mmol is considered clinically significant

proteinuria
 in diabetics microalbuminuria (ACR greater than 2.5 mg/mmol in men and ACR greater
than 3.5 mg/mmol in women) is considered clinically significant

8
Hyperkalaemia: management
Untreated hyperkalaemia may cause life-threatening arrhythmias. Precipitating factors should
be addressed (e.g. acute renal failure) and aggravating drugs stopped (e.g. ACE inhibitors).
Management may be categorized by the aims of treatment

Stabilization of the cardiac membrane

 intravenous calcium gluconate

Short-term shift in potassium from extracellular to intracellular fluid compartment

 combined insulin/dextrose infusion

 nebulised salbutamol

Removal of potassium from the body

 calcium resonium (orally or enema)

 loop diuretics
 dialysis

9
Diabetic nephropathy
Basics

 commonest cause of end-stage renal disease (ESRD) in the western world

 33% of patients with type 1 diabetes mellitus have diabetic nephropathy by the age of 40
years
 approximately 5-10% of patients with type 1 diabetes mellitus develop (ESRD)

The pathophysiology is poorly understood, however:

 changes to the haemodynamics of the glomerulus is thought to be key, which leads to an

increased glomerular capillary pressure
 histological changes include: basement membrane thickening, capillary obliteration,
mesangial widening. Nodulular hyaline areas develop in the glomuli - Kimmelstiel-Wilson
nodules

© Image used on license from PathoPic

Thickening of the basement membrane is seen alongside multiple Kimmelstiel-Wilson nodules

© Image used on license from PathoPic

Severe arteriolosclerosis is seen in the afferent arteriole on the left of the slide. Multiple, smaller acellular
nodules are seen in the glomerulus - Kimmelstiel-Wilson nodules. The tubular basement membrane is also
thickened

Risk factors for developing diabetic nephropathy

Modifiable Non-modifiable

Hypertension Male sex

Hyperlipidaemia Duration of diabetes
Smoking Genetic predisposition (e.g. ACE gene polymorphisms)

10
 Modifiable Non-modifiable

Poor glycaemic control

Raised dietary protein

Diabetic nephropathy: stages

Diabetic nephropathy may be classified as occurring in five stages*:
Stage 1
 hyperfiltration: increase in GFR
 may be reversible

Stage 2 (silent or latent phase)

 most patients do not develop microalbuminuria for 10 years
 GFR remains elevated

Stage 3 (incipient nephropathy)

 microalbuminuria (albumin excretion of 30 - 300 mg/day, dipstick negative)(ACR >2.5)

Stage 4 (overt nephropathy)

 persistent proteinuria (albumin excretion > 300 mg/day, dipstick positive)
 hypertension is present in most patients
 histology shows diffuse glomerulosclerosis and focal glomerulosclerosis (Kimmelstiel-
Wilson nodules)

Stage 5
 end-stage renal disease, GFR typically < 10ml/min
 renal replacement therapy needed

The timeline given here is for type 1 diabetics. Patients with type 2 diabetes mellitus (T2DM)
progress through similar stages but in a different timescale - some T2DM patients may progress
quickly to the later stages

11
ARPKD
 Autosomal recessive polycystic kidney disease (ARPKD) is much less common than
autosomal dominant disease (ADPKD).
 It is due to a defect in a gene located on chromosome 6

 Diagnosis may be made on prenatal ultrasound or in early infancy with abdominal masses
and renal failure.
 Newborns may also have features consistent with Potter's syndrome secondary to
oligohydramnios.
 End-stage renal failure develops in childhood.
 Patients also typically have liver involvement, for example portal and interlobular fibrosis.
 Renal biopsy typically shows multiple cylindrical lesions at right angles to the cortical
surface.

ADPKD
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited cause of
kidney disease, affecting 1 in 1,000 Caucasians. Two disease loci have been identified, PKD1
and PKD2, which code for polycystin-1 and polycystin-2 respectively

ADPKD type 1 ADPKD type 2

85% of cases 15% of cases

Chromosome 16 Chromosome 4

Presents with renal failure earlier

The screening investigation for relatives is abdominal ultrasound:

Ultrasound diagnostic criteria (in patients with positive family history)

 two cysts, unilateral or bilateral, if aged < 30 years

 two cysts in both kidneys if aged 30-59 years
 four cysts in both kidneys if aged > 60 years

12
 © Image used on license from PathoPic
Extensive cysts are seen in an enlarged kidney

ADPKD: features
Features

 hypertension
 recurrent UTIs
 abdominal pain
 renal stones
 haematuria
 chronic kidney disease

Extra-renal manifestations

 liver cysts (70%)

 berry aneurysms (8%)
 cardiovascular system: mitral valve prolapse, mitral/tricuspid incompetence, aortic root
dilation, aortic dissection
 cysts in other organs: pancreas, spleen; very rarely: thyroid, oesophagus, ovary

13
 © Image used on license from PathoPic
Extensive cysts are seen in an enlarged kidney

14
 © Image used on license from Radiopaedia
CT showing multiple cysts of varying sizes in the liver, and bilateral kidneys with little remaining normal renal
parenchyma.

15
Haematuria
The management of patients with haematuria is often difficult due to the absence of widely
followed guidelines. It is sometimes unclear whether patients are best managed in primary care,
by urologists or by nephrologists.

The terminology surrounding haematuria is changing. Microscopic or dipstick positive

haematuria is increasingly termed non-visible haematuria whilst macroscopic haematuria is
termed visible haematuria. Non-visible haematuria is found in around 2.5% of the population.

Causes of transient or spurious non-visible haematuria

 urinary tract infection

 menstruation
 vigorous exercise (this normally settles after around 3 days)
 sexual intercourse

Causes of persistent non-visible haematuria

 cancer (bladder, renal, prostate)

 stones
 benign prostatic hyperplasia
 prostatitis
 urethritis e.g. Chlamydia
 renal causes: IgA nephropathy, thin basement membrane disease

Spurious causes - red/orange urine, where blood is not present on dipstick

 foods: beetroot, rhubarb

 drugs: rifampicin, doxorubicin

Management

Current evidence does not support screening for haematuria. The incidence of non-visible
haematuria is similar in patients taking aspirin/warfarin to the general population hence these
patients should also be investigated.

Testing
 urine dipstick is the test of choice for detecting haematuria
 persistent non-visible haematuria is often defined as blood being present in 2 out of 3
samples tested 2-3 weeks apart
 renal function, albumin:creatinine (ACR) or protein:creatinine ratio (PCR) and blood
pressure should also be checked
 urine microscopy may be used but time to analysis significantly affects the number of red
blood cells detected
16
NICE urgent cancer referral guidelines

 of any age with painless macroscopic haematuria

 patients under the age of 40 years with normal renal function, no proteinuria and who are
normotensive do not need to be referred and may be managed in primary care
 aged 40 years and older who present with recurrent or persistent urinary tract infection
associated with haematuria
 aged 50 years and older who are found to have unexplained microscopic haematuria

Alport's syndrome
 Alport's syndrome is usually inherited in an X-linked dominant pattern*.
 It is due to a defect in the gene which codes for type IV collagen resulting in an abnormal
glomerular-basement membrane (GBM).
 The disease is more severe in males with females rarely developing renal failure
 A favourite question is an Alport's patient with a failing renal transplant. This may be caused
by the presence of anti-GBM antibodies leading to a Goodpasture's syndrome like picture
 Alport's syndrome usually presents in childhood.
 The following features may be seen:
 microscopic haematuria
 progressive renal failure
 bilateral sensorineural deafness
 lenticonus: protrusion of the lens surface into the anterior chamber
 retinitis pigmentosa
 renal biopsy: splitting of lamina densa seen on electron microscopy

*in around 85% of cases - 10-15% of cases are inherited in an autosomal recessive fashion with
rare autosomal dominant variants existing

17
Glomerulonephritides
Knowing a few key facts is the best way to approach the difficult subject of glomerulonephritis:

Minimal change disease

 typically a child with nephrotic syndrome (accounts for 80%)
 causes: Hodgkin's, NSAIDs
 good response to steroids

Membranous glomerulonephritis
 presentation: proteinuria / nephrotic syndrome / chronic kidney disease
 cause: infections, rheumatoid drugs, malignancy
 1/3 resolve, 1/3 respond to cytotoxics, 1/3 develop chronic kidney disease

Focal segmental glomerulosclerosis

 may be idiopathic or secondary to HIV, heroin
 presentation: proteinuria / nephrotic syndrome / chronic kidney disease

IgA nephropathy - aka Berger's disease, mesangioproliferative GN

 typically young adult with haematuria following an URTI

Diffuse proliferative glomerulonephritis

 classical post-streptococcal glomerulonephritis in child
 presents as nephritic syndrome / acute kidney injury
 most common form of renal disease in SLE

Rapidly progressive glomerulonephritis - aka crescentic glomerulonephritis

 rapid onset, often presenting as acute kidney injury
 causes include Goodpasture's, ANCA positive vasculitis

Mesangiocapillary glomerulonephritis (membranoproliferative)

 type 1: cryoglobulinaemia, hepatitis C
 type 2: partial lipodystrophy

Glomerulonephritis and low complement

Disorders associated with glomerulonephritis and low serum complement levels
 post-streptococcal glomerulonephritis
 subacute bacterial endocarditis
 systemic lupus erythematosus
 mesangiocapillary glomerulonephritis

18
Nephrotic syndrome
Triad of:
 1. Proteinuria (> 3g/24hr) causing
 2. Hypoalbuminaemia (< 30g/L) and
 3. Oedema
Loss of antithrombin-III, proteins C and S and an associated rise in fibrinogen levels predispose
to thrombosis. Loss of thyroxine-binding globulin lowers the total, but not free, thyroxine levels.

Nephrotic syndrome: complications

Complications
 increased risk of infection due to urinary immunoglobulin loss
 increased risk of thromboembolism related to loss of antithrombin III and plasminogen in
the urine
 hyperlipidaemia
 hypocalcaemia (vitamin D and binding protein lost in urine)
 acute renal failure

Minimal change disease

Minimal change disease nearly always presents as nephrotic syndrome, accounting for 75% of
cases in children and 25% in adults.
The majority of cases are idiopathic, but in around 10-20% a cause is found:
 drugs: NSAIDs, rifampicin
 Hodgkin's lymphoma, thymoma
 infectious mononucleosis
Pathophysiology
 T-cell and cytokine mediated damage to the glomerular basement membrane →
polyanion loss
 the resultant reduction of electrostatic charge → increased glomerular permeability to
serum albumin
Features
 nephrotic syndrome
 normotension - hypertension is rare
 highly selective proteinuria: only intermediate-sized proteins such as albumin and
transferrin leak through the glomerulus
 renal biopsy: electron microscopy shows fusion of podocytes
Management
 majority of cases (80%) are steroid responsive
 cyclophosphamide is the next step for steroid resistant cases
Prognosis is overall good, although relapse is common. Roughly:
 1/3 have just one episode
 1/3 have infrequent relapses
 1/3 have frequent relapses which stop before adulthood

19
Membranous glomerulonephritis
Membranous glomerulonephritis is the commonest type of glomerulonephritis in adults and is
the third most common cause of end-stage renal failure (ESRF). It usually presents with
nephrotic syndrome or proteinuria.

Renal biopsy demonstrates:

 electron microscopy: the basement membrane is thickened with subepithelial electron
dense deposits. This creates a 'spike and dome' appearance

Causes
 idiopathic
 infections: hepatitis B, malaria, syphilis
 malignancy: lung cancer, lymphoma, leukaemia
 drugs: gold, penicillamine, NSAIDs
 autoimmune diseases: systemic lupus erythematosus (class V disease), thyroiditis,
rheumatoid

Prognosis - rule of thirds

 one-third: spontaneous remission
 one-third: remain proteinuric
 one-third: develop ESRF

Good prognostic features include female sex, young age at presentation and asymptomatic
proteinuria of a modest degree at the time of presentation.

Management
 Immunosuppression: corticosteroids alone have not been shown to be effective. A
combination of corticosteroid + another agent such as chlorambucil is often used
 blood pressure control: ACE inhibitors have been shown to reduce proteinuria
 consider anticoagulation

© Image used on license from PathoPic

Silver-stained section showing thickened basement membrane, subepithelial spikes

20
Focal segmental glomerulosclerosis
Focal segmental glomerulosclerosis is cause of nephrotic syndrome and chronic kidney
disease. It generally presents in young adults.

Causes
 idiopathic
 secondary to other renal pathology e.g. IgA nephropathy, reflux nephropathy
 HIV
 heroin
 Alport's syndrome
 sickle-cell

Focal segmental glomerulosclerosis is noted for having a high recurrence rate in renal
transplants.

© Image used on license from PathoPic

Sclerosis of the glomerulus is seen next to Bowman's capsule

© Image used on license from PathoPic

Sclerosis is seen in the perihilar region of the glomerulus

21
IgA nephropathy
Basics
 also called Berger's disease or mesangioproliferative glomerulonephritis
 commonest cause of glomerulonephritis worldwide
 thought to be caused by mesangial deposition of IgA immune complexes
 there is considerable pathological overlap with Henoch-Schonlein purpura (HSP)
 histology: mesangial hypercellularity, positive immunofluorescence for IgA & C3

© Image used on license from PathoPic

Proliferation and hypercellularity of the mesangium is seen in the glomerulus

Differentiating between IgA nephropathy and post-streptococcal glomerulonephritis

 post-streptococcal glomerulonephritis is associated with low complement levels

 main symptom in post-streptococcal glomerulonephritis is proteinuria (although
haematuria can occur)
 there is typically an interval between URTI and the onset of renal problems in post-
streptococcal glomerulonephritis

Presentations
 young male, recurrent episodes of macroscopic haematuria
 typically associated with mucosal infections e.g., URTI
 nephrotic range proteinuria is rare
 renal failure

Associated conditions
 alcoholic cirrhosis
 coeliac disease/dermatitis herpetiformis
 Henoch-Schonlein purpura

Management
 steroids/immunosuppressants not be shown to be useful
22
Prognosis
 25% of patients develop ESRF
 markers of good prognosis: frank haematuria
 markers of poor prognosis: male gender, proteinuria (especially > 2 g/day), hypertension,
smoking, hyperlipidaemia, ACE genotype DD

© Image used on license from PathoPic

Immunostaining for IgA in a patient with HSP

Henoch-Schonlein purpura
Henoch-Schonlein purpura (HSP) is an IgA mediated small vessel vasculitis. There is a degree
of overlap with IgA nephropathy (Berger's disease). HSP is usually seen in children following an
infection.

Features
 palpable purpuric rash (with localized oedema) over buttocks and extensor surfaces of
arms and legs
 abdominal pain
 polyarthritis
 features of IgA nephropathy may occur e.g. haematuria, renal failure

© Image used on license from DermNet NZ

23
Treatment
 analgesia for arthralgia
 treatment of nephropathy is generally supportive. There is inconsistent evidence for the
use of steroids and immunosuppressants

Prognosis
 usually excellent, HSP is a self-limiting condition, especially in children without renal
involvement
 around 1/3rd of patients have a relapse

© Image used on license from DermNet NZ

© Image used on license from DermNet NZ

24
Membranoproliferative glomerulonephritis
Overview
 also known as mesangiocapillary glomerulonephritis
 may present as nephrotic syndrome, haematuria or proteinuria
 poor prognosis

Type 1
 accounts for 90% of cases
 subendothelial immune deposits of electron dense material resulting in a 'tram-track'
appearance
 cause: cryoglobulinaemia, hepatitis C

Type 2 - 'dense deposit disease'

 causes: partial lipodystrophy, factor H deficiency
 reduced serum complement
 C3b nephritic factor (an antibody against C3bBb) found in 70%

Type 3
 causes: hepatitis B and C

Management
 steroids may be effective

25
Granulomatosis with polyangiitis (Wegener's granulomatosis)
Granulomatosis with polyangiitis is now the preferred term for Wegener's granulomatosis. It is
an autoimmune condition associated with a necrotizing granulomatous vasculitis, affecting both
the upper and lower respiratory tract as well as the kidneys.

Features
 upper respiratory tract: epistaxis, sinusitis, nasal crusting, saddle-shape nose deformity
 lower respiratory tract: dyspnoea, haemoptysis
 rapidly progressive glomerulonephritis ('pauci-immune', 80% of patients)
 also: vasculitic rash, eye involvement (e.g. proptosis), cranial nerve lesions

Investigations
 cANCA positive in > 90%, pANCA positive in 25%
 chest x-ray: wide variety of presentations, including cavitating lesions
 renal biopsy: epithelial crescents in Bowman's capsule

Management
 steroids
 cyclophosphamide (90% response)
 plasma exchange
 median survival = 8-9 years

© Image used on license from Radiopaedia

Chest x-ray from a young male patient with granulomatosis with polyangiitis. Whilst the changes are subtle it
demonstrates a number of ill-defined nodules the largest of which projects over the dome of the right
hemidiaphragm. This nodule appears to have a central lucency suggesting cavitation

© Image used on license from Radiopaedia

CT of the same patient showing the changes in a much more obvious way, confirming the presence of at
least 2 nodules, the larger of the two having a large central cavity and and air-fluid level

26
Haemolytic uraemic syndrome
Haemolytic uraemic syndrome is generally seen in young children and produces a triad of:

 acute renal failure

 microangiopathic haemolytic anaemia
 thrombocytopenia

Causes
 post-dysentery - classically E coli 0157:H7 ('verotoxigenic', 'enterohaemorrhagic')
 tumours
 pregnancy
 ciclosporin, the Pill
 systemic lupus erythematosus
 HIV

Investigations
 full blood count: anaemia, thrombocytopaenia, fragmented blood film
 U&E: acute renal failure
 stool culture

Management
 treatment is supportive e.g. Fluids, blood transfusion and dialysis if required
 there is no role for antibiotics, despite the preceding diarrhoeal illness in many patients
 The indications for plasma exchange in HUS are complicated. As a general rule plasma
exchange is reserved for severe cases of HUS not associated with diarrhoea

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HIV: renal involvement
 Renal involvement in HIV patients may occur as a consequence of treatment or the virus
itself.
 Protease inhibitors such as indinavir can precipitate intratubular crystal obstruction
 HIV-associated nephropathy (HIVAN) accounts for up to 10% of end-stage renal failure
cases in the United States.
 Antiretroviral therapy has been shown to alter the course of the disease. There are five key
features of HIVAN:

1) massive proteinuria
2) normal or large kidneys
3) focal segmental glomerulosclerosis with focal or global capillary collapse on renal biopsy
4) elevated urea and creatinine
5) normotension

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Cholesterol embolisation
Overview
 cholesterol emboli may break off causing renal disease
 seen more commonly in arteriopaths, abdominal aortic aneurysms

Features
1) eosinophilia
2) purpura
3) renal failure
4) livedo reticularis

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Cytomegalovirus
 Cytomegalovirus (CMV) is one of the herpes viruses.
 It is thought that around 50% of people have been exposed to the CMV virus although it only
usually causes disease in the immunocompromised, for example people with HIV or those
on immunosuppressants following organ transplantation.

Pathophysiology
 infected cells have a 'Owl's eye' appearance due to intranuclear inclusion bodies

Patterns of disease
A) Congenital CMV infection
 features include:
1) growth retardation,
2) microcephaly
3) sensorineural deafness
4) pinpoint petechial 'blueberry muffin' skin lesions
5) encephalitis (seizures)
6) hepatosplenomegaly

B) CMV mononucleosis
 infectious mononucelosis-like illness
 may develop in immunocompetent individuals

C) CMV retinitis
 common in HIV patients with a low CD4 count (< 50)
 Presents with visual impairment e.g. 'blurred vision'.
 Fundoscopy shows retinal haemorrhages and necrosis, often called 'pizza' retina
 IV ganciclovir is the treatment of choice

D) CMV encephalopathy
 seen in patients with HIV who have low CD4 counts

E) CMV pneumonitis
F) CMV colitis

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Plasma exchange
Indications for plasma exchange
 Guillain-Barre syndrome
 myasthenia gravis
 Goodpasture's syndrome
 ANCA positive vasculitis e.g. Wegener's, Churg-Strauss
 TTP/HUS
 cryoglobulinaemia
 hyperviscosity syndrome e.g. secondary to myeloma

Peritoneal dialysis
Peritoneal dialysis (PD) is a form of renal replacement therapy. It is sometimes used as a stop-
gap to haemodialysis or for younger patients who do not want to have to visit hospital three
times a week.
The majority of patients do Continuous Ambulatory Peritoneal Dialysis (CAPD), which involves
four 2-litre exchanges/day.

Complications:
1) Peritonitis:
 Coagulase-negative staphylococci such as Staphylococcus epidermidisis the
most common cause.
 Staphylococcus aureus is another common cause
2) sclerosing peritonitis

Renal vascular disease

 Renal vascular disease is most commonly due to atherosclerosis (> 95% of patients).
 It is associated with risk factors such as smoking and hypertension that cause atheroma
elsewhere in the body.
 It may present as hypertension, chronic renal failure or 'flash' pulmonary oedema.
 In younger patients however fibromuscular dysplasia (FMD) needs to be considered.
 FMD is more common in young women and characteristically has a 'string of beads'
appearance on angiography.
 Patients respond well to balloon angioplasty

Investigation
 MR angiography is now the investigation of choice
 CT angiography
 conventional renal angiography is less commonly performed used nowadays, but may
still have a role when planning surgery

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Retroperitoneal fibrosis
Lower back pain is the most common presenting feature

Associations
 Riedel's thyroiditis
 previous radiotherapy
 sarcoidosis
 inflammatory abdominal aortic aneurysm
 drugs: methysergide

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Renal tubular acidosis
All three types of renal tubular acidosis (RTA) are associated with hyperchloraemic metabolic
acidosis (normal anion gap)

Type 1 RTA (distal)

 inability to generate acid urine (secrete H+) in distal tubule
 causes hypokalaemia
 complications include nephrocalcinosis and renal stones
 causes include idiopathic, RA, SLE, Sjogren's

© Image used on license from Radiopaedia

Abdominal x-ray showing nephrocalcinosis - a classical finding in type 1 RTA

Type 2 RTA (proximal)

 decreased HCO3- reabsorption in proximal tubule
 causes hypokalaemia
 complications include osteomalacia
 causes include:
1) idiopathic,
2) as part of Fanconi syndrome,
3) Wilson's disease,
4) cystinosis,
5) outdated tetracyclines

Type 4 RTA (hyperkalaemic)

 reduction in aldosterone leads in turn to a reduction in proximal tubular ammonium
excretion
 causes hyperkalaemia
 causes include hypoaldosteronism, diabetes

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Fanconi syndrome
Fanconi syndrome describes a generalised disorder of renal tubular transport resulting in:
 type 2 (proximal) renal tubular acidosis
 aminoaciduria
 glycosuria
 phosphaturia
 osteomalacia

Causes
 cystinosis (most common cause in children)
 Sjogren's syndrome
 multiple myeloma
 nephrotic syndrome
 Wilson's disease

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Renal stones:
Renal stones: risk factors
Risk factors
1) dehydration
2) hypercalciuria, hyperparathyroidism, hypercalcaemia
3) cystinuria
4) high dietary oxalate
5) renal tubular acidosis
6) medullary sponge kidney, polycystic kidney disease
7) beryllium or cadmium exposure

Risk factors for urate stones

1) gout
2) ileostomy: loss of bicarbonate and fluid results in acidic urine, causing the precipitation of
uric acid

Drug causes
1) drugs that promote calcium stones: steroids, loop diuretics, acetazolamide, theophylline
2) thiazides can prevent calcium stones (increase distal tubular calcium resorption)
Imaging
The table below summarises the appearance of different types of renal stone on x-ray
Type Frequency Radiograph appearance

Calcium oxalate 40% Opaque

Mixed calcium oxalate/phosphate 25% Opaque

stones

Triple phosphate stones* 10% Opaque

Calcium phosphate 10% Opaque

Urate stones 5-10% Radio-lucent

Cystine stones 1% Semi-opaque, 'ground-glass' appearance

Xanthine stones <1% Radio-lucent

*stag-horn calculi
 Involve the renal pelvis and extend into at least 2 calyces.
 They develop in alkaline urine and are composed of struvite (ammonium magnesium
phosphate, triple phosphate).
 Ureaplasma urealyticum and Proteus infections predispose to their formation

35
Renal stones: management
Acute management of renal colic

Medication
 the British Association of Urological Surgeons (BAUS) recommend diclofenac
(intramuscular/oral) as the analgesia of choice for renal colic*
 BAUS also endorse the widespread use of alpha-adrenergic blockers to aid ureteric
stone passage

Imaging
 patients presenting to the Emergency Department usually have a KUB x-ray (shows 60%
of stones)
 The imaging of choice is a non-contrast CT (NCCT). 99% of stones are identifiable on
NCCT. Many GPs now have direct access to NCCT

 Stones < 5 mm will usually pass spontaneously.

 Lithotripsy and nephrolithotomy may be for severe cases.

Prevention of renal stones

A) Calcium stones may be due to hypercalciuria, which is found in up to 5-10% of the general
population.
1) high fluid intake
2) low animal protein,
3) low salt diet (a low calcium diet has not been shown to be superior to a normocalcaemic
diet)
4) thiazides diuretics (increase distal tubular calcium resorption)

B) Oxalate stones:
 cholestyramine reduces urinary oxalate secretion
 pyridoxine reduces urinary oxalate secretion

C) Uric acid stones

 allopurinol
 urinary alkalinization e.g. oral bicarbonate

*Diclofenac use is now less common following the MHRA warnings about cardiovascular risk. It
is therefore likely the guidelines will change soon to an alternative NSAID such as naproxen

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Sterile pyuria
Causes
 partially treated UTI
 urethritis e.g. Chlamydia
 renal tuberculosis
 renal stones
 appendicitis
 bladder/renal cell cancer
 adult polycystic kidney disease
 analgesic nephropathy

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Renal cell cancer
 Renal cell cancer is also known as hypernephroma
 Accounts for 85% of primary renal neoplasms.
 It arises from proximal renal tubular epithelium

Associations*
1) more common in middle-aged men
2) smoking
3) von Hippel-Lindau syndrome
4) tuberous sclerosis

*incidence of renal cell cancer is only slightly increased in patients with autosomal dominant
polycystic kidney disease

Features:
1) classical triad: haematuria, loin pain, abdominal mass
2) pyrexia of unknown origin
3) left varicocele (due to occlusion of left testicular vein)
4) endocrine effects:
 may secrete erythropoietin (polycythaemia),
 parathyroid hormone (hypercalcaemia),
 renin,
 ACTH
5) 25% have metastases at presentation

Management
1) for confined disease a partial or total nephrectomy depending on the tumour size
2) alpha-interferon and interleukin-2 have been used to reduce tumour size and also treat
patients with metatases
3) receptor tyrosine kinase inhibitors (e.g. sorafenib, sunitinib) have been shown to have
superior efficacy compared to interferon-alpha

38
 © Image used on license from Radiopaedia
Coronal CT scan of a middle-aged woman with renal cell cancer. Note the heterogeneously enhancing mass
at the upper pole of the right kidney

Image sourced from Wikipedia© Image used on license from PathoPic

Left: normal kidney. Right: 'clear-cell' pattern of renal cell carcinoma

© Image used on license from PathoPic

'Clear-cell' pattern of renal cell carcinoma - clear cytoplasm, small nuclei

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Wilms' tumour
 Wilms' nephroblastoma is one of the most common childhood malignancies.
 It typically presents in children under 5 years of age, with a median age of 3 years old

Features:
 abdominal mass (most common presenting feature)
 painless haematuria
 flank pain
 other features: anorexia, fever
 unilateral in 95% of cases
 metastases are found in 20% of patients (most commonly lung)

Associations:
1) Beckwith-Wiedemann syndrome: an inherited condition associated with organomegaly,
macroglossia, abdominal wall defects, Wilm's tumour and neonatal hypoglycaemia.
2) as part of WAGR syndrome with Aniridia, Genitourinary malformations, mental
Retardation
3) hemihypertrophy
4) around one-third of cases are associated with a mutation in the WT1 gene on
chromosome 11

Management

 nephrectomy
 chemotherapy
 radiotherapy if advanced disease
 prognosis: good, 80% cure rate

© Image used on license from PathoPic

Histological features include epithelial tubules, areas of necrosis, immature glomerular structures, stroma
with spindle cells and small cell blastomatous tissues resembling the metanephric blastema

40
Renal transplant: HLA typing and graft failure

The human leucocyte antigen (HLA) system is the name given to the major histocompatibility
complex (MHC) in humans. It is coded for on chromosome 6.

Some basic points on the HLA system

 class 1 antigens include A, B and C.

 Class 2 antigens include DP,DQ and DR
 when HLA matching for a renal transplant the relative importance of the HLA antigens are
as follows DR > B > A

Graft survival

 1 year = 90%, 10 years = 60% for cadaveric transplants

 1 year = 95%, 10 years = 70% for living-donor transplants

Post-op problems

 ATN of graft
 vascular thrombosis
 urine leakage
 UTI

Hyperacute acute rejection (minutes to hours)

 due to pre-existent antibodies against donor HLA type 1 antigens (a type II hypersensitivity
reaction)
 rarely seen due to HLA matching

Acute graft failure (< 6 months)

 usually due to mismatched HLA. Cell-mediated (cytotoxic T cells)

 other causes include cytomegalovirus infection
 may be reversible with steroids and immunosuppressants

Causes of chronic graft failure (> 6 months)

 both antibody and cell mediated mechanisms cause fibrosis to the transplanted kidney
(chronic allograft nephropathy)
 recurrence of original renal disease (MCGN > IgA > FSGS)

© Image used on license from PathoPic

41
East Turkestan and the Communist occupation
Dr. Ragheb El-Sergany

23/01/2013 - 2:01pm

China today occupies East Turkestan (Xinjiang or Sinkiang). It is located in the center of Central
Asia. It is bordered by Russia to the north, Kazakhstan, Kyrgyzstan and Tajikistan to the west,
Pakistan and India to the south, China to the east, and Mongolia to the north east. The proportion of
Muslims there is 95%.

Islam was introduced to East Turkestan in 934 AD through the Uighur ruler, "Satuk Bughra Khan”,
who converted to Islam before he succeeded to the throne. After he became governor of the Uighur
state, he changed his name to the Muslim name ‘Abdul-Kareem Satuk. His conversion to Islam
encouraged most of the Turkmen and the people of central Asia to do the same and embrace Islam
as well. From then on, Turkestan became a major Islamic center in Asia.

The Chinese Communists occupied East Turkestan and followed the same policy of continuous
religious persecution against the Muslim population. The Chinese Communists pretended to
conduct cultural reform as they canceled the traditional Arabic letters in writings, considering it
“relics of the past". They destroyed 730 thousand books that were written in Arabic, including copies
of the Noble Quran, Hadeeth Books and religious books.

At the time of the 1949 takeover of China by the communists, the number of Muslims in East
Turkistan was about 2.3 million, and there were more than two thousand mosques. From the first
day of their rule, the Communist authorities carried out horrible massacres that were followed by
accommodating influxes of Chinese immigrants in a process of colonial settlement expansion. This
aimed at reducing the number of Muslims in the country, causing a demographic shift.

The Chinese canceled private property and enslaved Muslims. They officially banned the religion of
Islam in China and penalized anyone who performed Islamic acts of worship because communist
China saw Islam as the greatest obstacle to its grip over the region!

They isolated the Uyghurs, preventing them from leaving the country and preventing the entry of
any foreigners to them. They abolished religious institutions and demolished their buildings. They
turned mosques into clubs for their soldiers. The Uygurs, who had for centuries used Arabic script,
were forced to adopt the Latin alphabet. The communists made Chinese the official language and
replaced Islamic history with the teachings of Mao Zedong [also Mao Tse-tung].
42
They compelled Muslim women to marry Chinese non-Muslim men. Their deep hatred for Islam and
Muslims did not end at that point. Muslims were enslaved and reeled under the pressure of the
strong communist country. During the communist reign of terror, there was a violent campaign to
eradicate all traces of Islam and of the ethnic identity of all non-Chinese. They strove to obliterate
faith in the hearts of Muslims. When the Cultural Revolution erupted in China, the situation
worsened and the persecution of Muslims intensified. One of the slogans of the revolution was
"Cancel the teachings of the Quran"!

However, in the face of all this oppression, Muslims still held fast to their religion. Violent rebellions
by Chinese Muslims continued. China tried to hide the news about these revolutions from the whole
world and as always, Muslims refused to be silenced. One of these revolutions erupted in 1386
AH/1966 AD in the city of Kashgar whose Muslim residents attempted to perform the ‘Eed Al-Adh-
ha Prayer inside one of the mosques [mass worship was also banned]. Chinese troops prevented
them and carried out a horrible massacre against them.

Mass protests and violent riots spread like wildfire in the whole region and Muslims engaged in
guerrilla warfare against the Chinese forces. During one month of this revolution, about 75 thousand
Muslims gained martyrdom. The news reports do not stop about the uprisings of Muslims in East
Turkistan against the bloody inhuman Chinese occupation.
(Http://www.islamonline.net/arabic/history/1422/08/article25.shtml)
As a result, there was an intensification of arrests, and unfair mass “show trials” were grossly held in
all majority Uyghur areas of East Turkestan. Statistics indicate that more than three thousand
Uighurs were detained by Chinese authorities in a period of not more than two months after the
events of September 11, all with alleged political accusations. In the course of the so-called national
"strike hard" campaign against crime, nine consecutive public trials were held in Gulja, Aksu,
Kashgar, Khotan, Shahyar, Augtofan and Ansu. In these unfair trials, 13 Uighurs received death
sentences and were executed by firing squad on the same day.
Eastern Turkistan Information Center:
http://www.uygur.org/arabic/h_rights/tehlil_11_09_2001.htm

http://islamstory.com/en/node/42361

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