Modern Renal Transplantation

(present challenges and future prospects)

It has been known for several decades that transplantation is associated with both a survival and quality of
life benefit for recipients when compared with renal replacement therapy.

The length of time on dialysis before renal transplantation is associated with worse outcomes.

INCREASING THE DONOR POOL

There is an increasing disparity between numbers of patients active on the renal transplant list and the
availability of donor organs.

RENAL TRANSPLANT RECIPIENT (PREOPERATIVE PREPARATION)

 The transplant recipient will have undergone a cardiovascular, anatomical and immunological
work up.
 Our current policy is that patients with diabetes or known coronary disease should have had a
coronary angiogram with a view to percutaneous or surgical revascularisation within the previous
2 years.
 Haemodialysis patients are not routinely dialysed on the day of the operation unless they have
pronounced hyperkalaemia.
 Some historical data to suggest that those patients dialysed before transplantation have a worse
outcome.
 This is most likely due to reduced intravascular volume leading to reduced graft perfusion.
 Patients on PD will drain out their peritoneal dialysate before the operation.

(OPERATIVE TECHNIQUE)

A renal transplant is essentially three anastomoses :artery, vein and ureter.

The donor artery is usually attached to the recipient internal iliac artery (end-to-end) or the external iliac
artery (end-to-side); the donor renal vein is anastomosed to the external iliac vein.

The donor ureter is passed through the posterior wall of the bladder and sutured to the mucosa
(ureterneocystotomy) with a ureteric JJ stent in situ.

ORGAN PRESERVATION

Donor kidneys are perfused with preservation fluid which contain –

 buffers to maintain pH,

 metabolically inert compounds to increase tonicity,
 free radical scavengers and
 other nutrients.

In the case of a deceased donor kidney, the organ is then sealed in a plastic bag and kept on ice during
transit until preimplantation preparation in theatre.
The manner in which donor organs are transported, could lead to better graft function.

INTRAOPERATIVE AND IMMEDIATE POSTOPERATIVE MANAGEMENT

Fluid balance

Good graft perfusion it is essential that the patient is well hydrated.

Who has been on long term haemodialysis is likely to have an enlarged heart with diastolic dysfunction
and will be at risk of pulmonary oedema with only modest fluid overload.

There are no randomised controlled trials to test for superiority of crystalloid or colloid in this patient
group.

Dopamine and diuretics

Dopamine can be used to support a blood pressure to above 130/80 mm Hg and potentially improve graft
perfusion in addition to its diuretic effects.

High dose diuretics are commonly used intra- and postoperatively to increased urine flow rates and to try
to prevent plugging of the renal tubules.

Anticoagulation

Routine postoperative deep vein thrombosis (DVT) prophylaxis with either unfractionated subcutaneous
heparin or low molecular weight heparin is undertaken once the surgeon is satisfied that there is no
delayed problem with haemostasis.

Infection

Perioperative prophylaxis against wound infection (for example, vancomycin and ciprofloxacin).

Additional prophylaxis includes agents to prevent pneumocystis (for example, co-trimoxazole),

cytomegalovirus (for example, valganciclovir) and oral fungal infection (nystatin).

These tail off over 3–6 months post-transplant.

Causes of abdominal pain in transplant patients

1. Acute rejection
2. Acute abdomen causes
3. Renal stones
4. Urinary leakage
5. Vascular thrombosis/embolism

General care

Inpatient stay is 1 week living related and 1–2 weeks deceased donor.

THE LIVING DONOR FOLLOW-UP

Part of the success of living donation is the package of care offered to the donor.

To the increase in living donation is improved surgical technique for transplant nephrectomy: a smaller
scar, less pain and a shorter hospital stay is clearly attractive to a potential donor.

IMMUNOSUPPRESSIVE THERAPY

Main site of action

Maintenance Immunosuppressive Drugs (MSC regimen)

• Glucocorticoids
 • Calcineurin inhibitors
– Cyclosporine (CsA), Tacrolimus (FK506)
• Antiproliferative agents
– Azathioprine, Mycophenolate Mofetil (MMF)
• Anti-lymphocytes polyclonal antibodies
– ATG, thymoglobulin
• Anti-CD3 monoclonal antibodies
– OKT-3
• Anti-IL2R monoclonal antibodies
– Basiliximab, Daclizumab

Calcineurin inhibitors

The mainstay of immunosuppression and their use can be credited with decreased rates of rejection and
better short and long term survival in the last decade.

Ciclosporin (CsA or CyA)

Ciclosporin binds to cyclophilin and this complex inhibits calcineurin phosphatase and T cell activation.

Tacrolimus (FK506)

The mechanism of tacrolimus action is similar to that of CyA.

It is more effective in preventing acute rejection than CyA.

Antiproliferative agents

Azathioprine is derived from 6-mercaptopurine which interferes with DNA synthesis.

Despite NICE recommendations for azathioprine use in low risk transplantation,it has been abandoned by
many units in favour of mycophenolate mofetil.

Mycophenolic acid (MPA/MMF/Myfortic)

 (MPA) is a non-competitive and selective antagonist to inosine monophosphate dehydrogenase,

which is an enzyme important in the de novo synthesis of purines.
 The routine use of MPA is not recommended by NICE.
 But the use of MMF is associated with reduced acute rejection and prolongation of allograft
survival.

mTOR inhibitors
(rapamycin, sirolimus, everolimus)

It inhibits the proliferation of T cells.

Because it is not nephrotoxic, rapamycin has been used as replacement for calcineurin inhibitors in both
the acute and chronic setting.
It has also been used with calcineurin inhibitors in place of antiproliferative drugs.
Although the predominant benefit is the reduction of calcineurin toxicity, it has been shown to be superior
to CyA and steroids (both with and without azathioprine) in the prevention of acute rejection, but this was
associated with an increased risk of infection.

Corticosteroids
(prednisolone, methylprednisolone)

Corticosteroids act as agonists of glucocorticoid receptors at low doses, but at higher doses their effects
become non-specific.

The mainstay of immunosuppression throughout the evolution of transplantation.

Associated with deleterious side effects such as susceptibility to infection, weight gain,NODAT,
hypertension, hyperlipidaemia, and osteopenia.

Monoclonal and polyclonal antibodies

IL2 receptor antagonists (daclizumab, basiliximab)

monoclonal antibodies to CD25 is safe and effective as an adjunct to conventional immunosuppression at
induction.
Their use is recommended in the NICE technology appraisal.
Antithymocyte globulin

It is commonly used for induction therapy in the USA and Europe, but less commonly in the UK.
It may also be used to treat steroid resistant rejection.
Campath 1H (alemtuzumab)
may be a useful tool for tolerance induction.

TAILORING IMMUNOSUPPRESSION

Immunosuppression minimisation has become the focus of many progressive renal transplant
programmes both in the UK and overseas.

CARDIOVASCULAR RISK

The most common cause of death after transplantation remains cardiovascular in aetiology.

Recently presented data showing a reduction in cardiovascular events after transplantation with
the use of –

 a steroid sparing immunosuppressive regimen,

 aggressive treatment of cardiovascular risk factors, and
 pre-transplant cardiovascular screening and management using coronary angiography and
revascularisation.

SOLID ORGAN TUMOURS

The incidence of the most common solid organ cancers are 2–3 times higher in the transplant recipient
than the general population at 3 years.
Chronic uraemia has an immune modulatory effect which may also be carcinogenic.

Conventional risk factors such as cigarette smoking add to the risk of malignancy in all our patients.

VIRAL TUMOURS

Cervical interstitial neoplasia as well as anal interstitial neoplasia are also associated with HPV.

Appropriate cervical screening is recommended.

PTLD, in the form of a B cell lymphoma, may also be virally driven by Epstein–Barr virus (EBV).

INFECTIONS

 The most common infection is of the urinary tract and this may be related to the presence of a
ureteric stent.
 A recurrent or severe infection may necessitate early stent removal.
 Fungal infections can be particularly severe, and if fungus is detected the presence of invasive
disease should be considered.
 Recent random controlled trial data suggest that prophylaxis against cytomegalovirus (CMV),
provides superior allograft survival than monitoring for viraemia and pre-emptive treatment.

INVESTIGATION OF GRAFT DYSFUNCTION

The approach to the differential, as ever, will be history and examination, urinalysis, blood tests, imaging
and histology.

History and examination

Weighing the patient- intravascular volume depletion is the most common single cause of graft
dysfunction.

Infection is also an important cause of graft dysfunction.

Urinalysis

 A urine dipstick reveal a urinary tract infection (UTI), renal inflammation

(proteinuria/haematuria) or new onset diabetes (glycosuria).
 Microscopy may be warranted for leucocytes (UTI), casts (nephritis) or decoy cells (BK
nephropathy).
 Culture for bacterial, mycobacterial or fungal pathogens or viral polymerase chain reaction (PCR)
may also be appropriate.

Blood tests

Most patients will require a CMV PCR or IgM enzyme linked immunosorbent assay (ELISA) because
CMV disease can be clinically silent.
Imaging

All patients with graft dysfunction must have a Doppler ultrasound scan (USS) to rule out urinary tract
obstruction and to demonstrate graft perfusion.

A recent evaluation of the renal artery anatomy—for example, by magnetic resonance angiogram (MRA)
—may be desirable.

If the renal tract is dilated this may need decompressing with a transplant nephrostomy and further
evaluation with a nephrostogram or computed tomography of the kidney, ureter and bladder (CT-KUB).

Biopsy

Transplant biopsy remains the gold standard for diagnosing intra-renal causes of graft dysfunction.

Acute rejection can be diagnosed by light microscopy alone.

Electron microscopy can assist with the diagnosis of transplant glomerulopathy, and immunostaining may
be indicated if recurrence of a primary disease such as lupus is suspected.

Rejection

Simply, rejection can be described according to the main pathological process identified by histology—
either cellular or antibody mediated.

This is important because it guides therapy.

In general, cellular rejection is responsive to steroids (usually 0.5 g of methylprednisolone per day for 3
days) and this is usually accompanied by an increase in target values of other immunosuppressive drugs
such as calcineurin inhibitors.

Antibody mediated rejection is less likely to respond to steroids and can be treated with plasma exchange
to remove the antibody and intravenous immunoglobulin.

 Chronic allograft dysfunction is likely to have non-immune components.

 Such as treating hypertension with an angiotensin converting enzyme (ACE) inhibitor.
 There is an ongoing immune process by the histological picture-cellular or antibody mediated.
 The latter is detected by a transplant glomerulopathy on biopsy or by the presence of de novo
anti-donor antibodies.Treatment at this stage is uncertain.
Tolerance
Tolerance is the absence of an anti-donor immune response while retaining an otherwise intact
immune system in the absence of any exogenous immunosuppressants.

Campath is extremely efficient in depleting T cells and there is some hope that this may be a tool towards
tolerance induction.
Low incidence of acute rejection and good medium term allograft survival have been published using
Campath,
It is clear that Campath alone does not induce tolerance in humans, and adjunctive therapy with
calcineurin inhibitors is required early post-transplant.
The use of rapamycin monotherapy with Campath results in higher rates of rejection.
RECURRENCE OF NATIVE DISEASE

Treatment may be possible—for example plasma exchange for early recurrence of focal segmental
glomerular sclerosis (FSGS).

DE NOVO RENAL DISEASE

 Diabetic nephropathy or a thrombotic microangiopathy that might be precipitated by

immunosuppression or other insult.
 Patients with Alports syndrome with a renal transplant, their immune system has never seen the
α3 chain of type IV collagen of the glomerular basement membrane (GBM).
 Therefore can suffer de novo anti-GBM disease.

FERTILITY AND PREGNANCY


Young women on dialysis are rarely fertile, and if they become pregnant, the chance of delivering
a healthy baby is low.
 In general we counsel against pregnancy in the first year (sometimes 2 years).
 Calcineurin inhibitors are the mainstay of immunosuppression in the pregnant transplant patient.
 Mycophenolate and sirolimus should be replaced with azathioprine or steroids;
 ACE inhibitors should be switched to methyldopa, labetolol or nifedipine; and
 proton pump inhibitors should be switched to ranitidine.
 if this is associated with a hypercoagulable state—aspirin or low molecular weight heparin may
be indicated.
CONCLUSION
 Dialysis should be reserved as a therapy for those unsuitable for transplantation or those who
await transplantation.
 Careful patient and therapeutic monitoring of the newer oral immunosuppressive agents, together
with the avoidance or sparing of steroids, should diminish perceived concerns regarding infective
and malignant potential.

Main messages

The prevalence of end stage renal failure is increasing.

The number of transplants per year is relatively static, although numbers awaiting transplantation are
growing.

Transplantation is cost effective and more importantly improves mortality and morbidity.

The donor pool needs to be expanded.

Outcomes with live transplantation are superior to deceased donor transplantation.

Timing of transplant

 Shouldnot be placed on waiting list while any degree of useful stable native function remains .
  Should not evade earlier immunosuppressive therapy than necessary.
 Should placed on list during months immediately before the need for dialysis.

Donor selection

 Exclusion of transmissible d/s

 Renal function assessment USG
 HLA compatibility

Pre-transplant work-up in recipient

 CP, platelets  ECG, cardiac catheterization and

 PT, APTT intervention if necessary
 Liver/ renal profile  ABO and HLA testing
 Hepatitis / infection screening  Panel reactive Ab screening
 Malignancy screening  USG , M

Indications for renal transplantation

1. Treatment of choice for most cases of ESRF unless contraindicated

Contraindications

Absolute –intractable cardiorespiratory d/s

Progressive neurological d/s
Major psychiatric problems
HIV
Drug addiction
Persistent coagulation d/o

Relative –original renal d/ s of high recurrence (FSGS, IgA, Goodpasture’s $, MCGN 2)

Age
Malignancy
HBV, HCV

Advantages and disadvantages of transplant over dialysis

1. Free of dialysis
2. Cheaper than dialysis in long term
3. Free of dietary constraint
4. Improvement of anaemia
5. Improvement of bone d/s
6. Improvement of quality of life
7. Prolong survival

Complications
Acute tubular necrosis (ATN)
- ATN is the commonest cause of cadaveric graft dysfunction (up to 40-50%), particularly after
asystolic donation and prolonged cold ischaemia time (> 24 horus).
- Kidneys from elderly (>55 years) donors and those with a history of hypertension are liable to
develop ATN.
- Delayed graft function due to ATN is associated with worse long-term outcome and also
predisposes the graft to rejection.
- It is usual practice to use induction with antibodies and use 50% of the starting dose of
calcineurin inhibitors in recipient of grafts at high risk for ATN.
Technical failures
- There may be occlusion or stenosis of the arterial anastomosis, occlusion of the venous
anastomosis, and urinary leaks owing to damage to the lower ureter, or defects in the anastomosis
between ureter and recipient bladder.
- If urine output drops, these diagnoses should be considered using Doppler ultrasonography,
DTPA scanning and / or renal angiography.
- Surgical re-implantation may be required.

Acute rejection (AR)

- AR is seen in up to 30% of transplant recipients and usually presents with declining renal
function within the first 3 months. Renal biopsy confirms the diagnosis and also assesses the severity.
- Therapy in cellular rejection is high - dose pulse steroid; in acute vascular rejection, ATG, ALG
or OKT3 is used.
- More than one rejection within the first 3 months, delayed rejection and failure of serum
creatinine to return to baseline are associated with worse long - term outcome.

Infections
- In the first month post - transplantation, infections tend to be from bacterial sources seen typically
in the surgical population.
- Cytomegalovirus (CMV) infectioris develop weeks or months after transplantation in 70% of
CMV-seronegative recipients receiving grafts from a sero-positive donor and in patients receiving
biological agents (antibodies) as induction or therapy for rejection, unless prophylaxis with valganciclovir
or valaciclovir is given. Prophylaxis is also routinely given against Pneumocystis carinii (co-trimoxazole)
and oral candidiasis (nystatin or amphotericin lozenges).
- Polyomavirus infections (BK nephropathy) result in graft dysfunction and eventual loss due to
mainly tubulointerstitial nephritis.
- There is no known specific treatment with the exception of tapering immunosuppression.

Post - transplantation lymphoproliferative disorders

- Epstein - Barr virus - associated malignancies are common in patients who received biological
agents and in children.
- Cautious tapering of ciclosporin or tacrolimus and monitoring for the reappearance of cytotoxic
lymphocytes has improved the outcome.

Chronic allograft nephropathy (CAN)

- CAN remains the most common cause of late graft failure.
- The process is mediated by immunological and non -immunological factors and results in a
progressive irreversible decline in graft function with mild to modest proteinuria (<3 g/day)
- Unfortunately there is no established therapy of proven efficiency.

Malignancy
- Immunosuppressive therapy increases the risk of skin tumours including basal and squamous cell
carcinoma.
- In white recipients, exposure to ultraviolet light should be minimized and sun-block creams
employed.
- Other common cancers are renal, cervical and vaginal. In female recipients, regular yearly
cervical smears should be carried out.

Cardiovascular disease
- Cardiovascular disease is the cause of death post-transplantation in 50% of case.
- This is due to increased incidence of hypertension, obesity, diabetes and insulin resistance lipid
disorders.
- Use of a statin (fluvastatin) was associated with reduction in cardiac end - points (myocardial
infarction or revascularization) post-transplantaiton but overall mortality remained unchanged in a
randomized prospective study.

Post - transplant osteoporosis

- This is common following transplantation owing to treatment with steroids.
- Maximum bone loss occurs with - in the first 3 months and regular DXA scans are necessary,
alphacalcidol with or without calcium carbonate have proven to be effective in control studies.

Recurrent disease
- Recurrence of renal disease is surprisingly common.
- Primary FSGS often recurs and causes early graft loss.
- Mesangiocapilary GN, diabetic nephropathy and IgA nephropathy also commonly recur but
seldom cause renal insufficiency.

Causes of early dysfunction

1. Delayed primary function d/t prolonged cold ischemic time (should be < 24 hrs)
2. Vascular thrombotic complications
3. Urological complications
4. Lymphocele
5. Hyperacute rejection due to presensitized T cell in recipients
6. Acute rejection (< 6 months)
7. Cyclosporine toxicity
8. Infections (viral, bacteria, PCP ,fungal)
Causes of late dysfunction
 Chronic rejection
 Cyclosporine toxicity
 Recurrence of primary renal d/s
Good prognosis in kidney from young donor
 Asain > Caucasian>Negros
 1st transplant> 2nd trraansplant
 Good HLA matching

Immunologic factors Nonimmunologic factors

1. Poor HLA matching and previous 1. Older donor or poor graft quality
sensitization 2. Brain-death injury,preservation injury, or
2. Delayed graft function ischemic injury
3. Episodes of acute rejection 3. Acute peritransplantational injuries
4. Subacute and chronic alloimmune response 4. Delayed graft function
5. Noncompliance of patient 5. Hypertension
6. Suboptimal immunosuppression 6. Hyperlipidemia
7. Chronic toxic effects of cyclosporine or
tacrolimus

STRATEGIES TO PREVENT LATE RENAL ALLOGRAFT LOSS

CURRENT STRATEGIES
1. Improvement in perioperative management (minimizing early allograft injury)
2. Pharmacologic prevention of acute rejection
3. Treatment of severe or refractory acute rejection
4. Definition of the optimal long-term dose of calcineurin inhibitor
5. Discontinuation of corticosteroids in patients in stable condition
6. Treatment of hypertension and hyperlipidemia
FUTURE STRATEGIES
1. Avoidance of calcineurin inhibitors or corticosteroids
2. Induction of donor-specific hyporesponsiveness (requiring minimal maintenance
immunosuppression)
3. Induction and maintenance of tolerance (requiring no maintenance immunosuppression)

Polycystic kidney Disease / Renal Transplant

Long Case

History

Age - It has a worldwide distribution. In the white population the disease

appears to occur in about 1 in 400 to 1 in 1000 people.
- Although the disease is rare in Africa and less common in American
blacks than whites, the incidence of end-stage renal disease due to
autosomal dominant polycystic kidney disease is similar in blacks and
whites.
- ADPKD is an important cause of renal failure with 77% of patients
dying or reaching end-stage renal disease by the age of 70 years.

Name
Age
Sex
Address
Marital Status
Occupation
 Date of Admission
 Duration of Hospitalization

HOPI
1. When the dx was made.
2. Presenting features
3. Initial treatment
4. disease progression
5. Alteration in treatment over time and any complications encountered.

Polycystic Kidneys
History
- Acute loin pain and/or haematuria (owing to haemorrhage into a cyst, cyst infection or urinary
stone formation).
- Loin or abdominal discomfort (due to increasing size of kidneys).
- Family history of polycystic kidney disease (as the condition is autosomal dominant with nearly
100% penetrance).
- Complications of hypertension
- Stroke (due to ruptured berry aneurysm)
- Family history of brain aneurysm (the prevalence of intracranial aneurysms increases from 5% to
20% when there is a family history).

Transplanted Kidney
- History of chronic renal failure - determined duration, aetiology(diabetes, hypertension,
glomerulonephritis).
- History of haemodialysis
- History of arteriovenous fistula.
- History of transplanted kidney.

System Review
1. CVS
Breathlessness, Chest pain, Plapitation, Syncope, Ankle swelling

2. Respiratory
Cough, Sputum, Haemoptysis, Chest pain related to respiration & coughing, Wheezing

3. Alimentary
Painful mouth, dysphagia, Indigestion, Abdominal pain, Vomiting, Anorexia, Weight loss,
Diarrhoea,Constipation, Colour of stool

4. CNS
Headache, Fits, Inpaired consciousness, Numbness, Paraesthesia, Hearing symptoms, Visual symptoms,
Sleep pattern

5. Urogential
Pain on passing urine, Frequency of passing urine by day night (nocturia), (Male – appropriate age)
Prostatic symptoms, (Female) Stress/urge incontinence, Abnormal colour of urine, amount of urine/day,
Libido, Urethral discharge
6. Haematoligical
Symptoms of anaemia (Lightheadacheness, dizziness, lethargy, palpitation, dysprioea on exeration),
Bleeding manifestations skin-red spots mucosa – epistaxis, gum bleeding haematemesis malena, Oral
ulcers, Bone pain

7. Locomotor
Jiont pain or stiffness, Muscle pain, Muscle weakness,

8. Endocrine
Heat intolerance, Cold intolerance, Prominence of eyes, Changes in sweating

Past med: H.O

1. Relevant to the present illness (Cause and complications)
2. Routine (a) Diabetes, (b) Hypertension, (c) Heart disease, (d) Tuberculosis, (e) Others
- P.U, Renal dis, drug reaction HT, DM
- TB, STD, malobsorption, inflarn: bowel disease H/O hospitalization

Past Surgical History

(a) Surgical disease (b) Operations (c) Accidents

Personal and Social History

- Education , Occupation, Family income, Marital status, Number of children, Alcohol,
Smoking, Betel nut chewing, Sexual history, House

Family History
Alive, Dead, Age, Anyillness, Cause of death, Malignancies, Others
Father, Mother Wife / Husband
Siblings
Children

Drug History
Allergy (Hypersensitivity), Self medications, (Indigenous), Recent medicaitons for present illness,
Regular medications, Prophylactic medications, Vaccinations, Abuse/addict complications.

Obstetric History
Age of marriage, Gravida, Parity, Contraception, Methods:, Pills, Depot, Authorized, sterilization, Others

Gynaecological History
Age of Menarche, Menopause, LMP, Cycle, Amount, Any discharge PV,
ovarian cyst

Examination
Short Case
Polycystic Kidney Disease
Points in the examination
- Evidence of renal replacement therapy - fistulas in the forearm, catheter scars on the abdomen.
- Bilateral or unilateral bimanually palpable mass in the abdomen; often one or both kidneys
have been removed, resulting in nephrectomy scars
- Liver cysts causing irregular hepatomegaly
- Kidney transplant:
- Characteristic J-shaped scar in the iliac fossa
- Side - effects of immunosuppressive therapy - gum hypertrophy, skin tumours
- Anaemia is uncommon in these individuals due to the overproduction of erythropoietin
- Neutrological deficit - associated berry aneurysms, resulting in subarachnoid haemorrhage in the
minority of patients
- Hypertension - ask to measure the blood pressure; is the patient on β - blockers? (bradycardia
and cold peripheries)

Differential diagnosis of a renal mass

- Renal cell carcinoma - associated with weight loss, lymphadenopathy and paraneoplastic
syndromes (polycythaemia and hypercalcaemia)
- Hydronephrosis
- Adrenal mass - phaeochromocytoma, carcinoma
(Candidates must be ale to distinguish between a renal mass and liver/spleen)

Aetiology
- Polycystic kidney disease is usually autosomal dominant (chromosome 16), although an
autosomal recessive form of the disease also occurs (15% of causes). It occurs in 1 in 400 - 1000 people.
Cysts are invariably present by 18 years of age, and can also occur in the liver, pancreas and spleen. The
cysts are easily visible on ultrasound scannig.

Symptoms
- Acute loin pain and/or haematuria
- Abdominal discomfort
- Headaches - sudden onset may be related to subarachnoid haemorrhage
- Symptoms of renal failure occur as renal function declines with time; patients are at increased
risk or urinary tract infection (UTIs) and pyelonephritis.

Investigations
- U+E, FBC
- Urinalysis
- Ultrasound
- Intravenous urography (IVU) for hydronephrosis
- Magnetic resonance imaging (MRI) cerebral angiogram - berry aneurysms
What are the criteria for diagnosis of polycystic kidney disease using ultrasonography?
 The presence of at least two renal cysts (unilateral or bilateral) in individuals at risk and younger tan
30 years
 among those aged 30 - 59 years the presence of at least two cysts in each kidney, and
 among those aged 60 years and abvoe at least four cysts in each kidney should be required.

Management
- Once the disease is established, patients required regular renal monitoring as 80% of patients
have endstage renal failure by their 8th decade; a sudden decline in renal function can occur due to
hypertension or pyelonephritis.
- Hypertension should be carefully controlled, as it may result in deterioration of renal function and
predispose to an intractranial event.
- Family members should be counselled and screened with ultrasound - cysts can be identified at
about 18 years of age. Currently, there is no widely available genetic test.
- A positive family history of subarachnoid haemorrhage requires MRI scanning of the brain, as
20% will have a cerebral aneurysm.

What are the poor prognostic factors in ADPKD?

Patients are liable to progress more rapidly if they are male, or have polycystin - 1 mutations,
early onset hypertension, episodes of gross haemautria or family history of hypertension in the unaffected
patient but these only account for a fraction of the variability of disease progression.

What are the causes of death in these patients?

One third of adult patients die from renal failure; another third die from the complications of
hypertension (including heart disease, intracerbral haemorrhage and rupture of berry aneurysm). The
remaining third die from unrelated causes.
Short Case
Transplanted Kidney
Points in the examination
- Signs of previous renal replacement therapy (forearm fistula(functioning or not) or peritoneal
dialysis scars).
- Evidence of immunosuppressive therapy (gum hypertrophy, cushingoid appearance, skin
tumours)
- Mass in the iliac fossa, with overlying scar J - shaped consistent with transplanted kidney
- Assess graft function - uraemia, shortness of breath, graft tenderness

- Aetiology of the renal failure

- Lipodystrophy associated with membranous glomerulonephritis
- Polycystic kidneys in the abdomen
- Signs of diabetes, eg. glucometer, glucose stix, foot ulcers and poor vision.
- Other autoimmune conditions, eg. SLE (rashes), vitiligo

Differential diagnosis for a mass in the iliac fossa

- Crohn's disease - mouth ulcers, anal disease, abdominal scars, skin rashes.
- Primary malignancy (bowel, ovarian) - lymph nodes, hepatomegaly, cachexia
- lliac TB mass - fever, lymph nodes, evidence of respiratory disease
- Appendicular abscess
- Caecal carcinoid

Causes of endstage renal failure in the UK

- Diabetes
- Glomerulonephritis
- Chronic pyelonephritis
- Polycystic kidneys
- Interstitial nephritis
- Hypertension

Symptoms
- Most patients in the exam will have a transplanted kidney that is functioning well. Symptoms
pointing towards graft rejection include tenderness over the graft, fever, hypertension, increased shortness
of breath (fluid retention) and decreased urine output.

Investigations
Diagnosis of chronic renal failure (CRF)
- Urea and electrolytes (U+E) - elevated creatinine, acidosis, hyperkalaemia
- FBC - normocytic, normochromic anaemia
- Bone profile - hypocalcaemia, hyperphosphataemia
- 24 hr creatinine clearance
Aetiology
- Renal ultrasound - exclude obstruction
- Glucose, HbA1
- FBC, ESR - autoimmune disease, myeloma
- Urinalysis - proteinuria, red - cell casts, pyuria, cytology
- Antinulear antibody (ANA), double - stranded (ds) DNA, complement C3/C4 antineutrophil
cytoplasmic antibody (ANCA), anti-GBM (glomerular basement membrane), rheumatiod factor (RF)
levels
- Serum protein and urine electrphoresis
- Atistreptolysin O (ASO) titre
- Hepatitis B and C serology
- Prostate - specific antigen (PSA)
- Technetium - 99 m labelled DTPA (diethylenetriamine penta - acetic acid) renogram or MAG3
(mercaptoacetyl triglycine) renogram - gives the percentage contribution of each kidney to the glomerular
filtration rate (GFR)
- Renal biopsy

Management f renal transplant patients

- Monitor serum creatinine levels.
- Observe for signs of rejection and secondary malignancy.
- Immunosuppressive drugs.
- Address cardiovascular risk factors.

Side - effects of immunosuppressive therapy

- Opportunistic infections - e.g herpes zoster virus, (Pneumocystis carinii pneumonia, (PCP),
cytomegalovirus (CMV)
- Malignancy - skin, lymphoma
- Ciclosporin - gum hypertrophy, hypertension, nephrotoxicity, CNS disturbance
- Azathioprine - hypersensitivity reactions and bone marrow suppression
- Tacrolimus - similar to ciclosporin, more CNS disturbance
- Glucocorticoids - Cushing's syndrome, osteoporosis, avascular necrosis.

Points of interest
- 2000 transplants take place in the UK every year, with an 80% 5 year success rate for live donors
with one matched haplotype. Success rates are lower for cadaver kidneys. HLA - matching improves graft
survival and exposes an individual to fewer antigens, thus making a second transplant easier, if required.
In constrast, the 5 - year survival of a 60 year - old, non - diabetic dialysis patient is approximately 60%
(30% for diabetics).
- Rejection is most likely to take place in the first 3 months.
Immunosuppressive drugs such as ciclosporin, azathioprine, tacrolimus and glucocorticoids are
used. Early signs of rejection include declining renal funciton and pain, but these can also be due to
infection or nephrotoxicity. Many patients will require a biopsy to establish the cause.
- Focal segmental glomerulonephritis can recur in transplanted kidneys. As this results in graft loss
in only 15% of affected patients it is not a contraindication to transplantation.
Continuous ambulatory peritoneal dialysis (CAPD)
- The peritoneum acts as the semipermeable membrane; dialysis takes place via a peritoneal
catheter. Small abdominal scars remain after removal. Dialysis is required up to three times per day and
involves attaching bags to the peritoneal catheter. The main risk is infeciton. Contraindications include
previous abdominal surgery or diverticular disease

Haemodialysis
- This is performed via a fistula in the forearm; patients often have more than one fistula. Dialysis
usually occurs for 3 hours, there times a week in hospital. Satellite dialysis units hve improved patient
access. An adequate blood pressure and good functioning cardiovascular system are required for
haemodialysis as fluid shift is more intense.

CAPD vs. haemodialysis

- CAPD is more flexible and can be performed at home. However, there is a greater risk of
infection and the process needs to be performed three times a day.
- Haemodialysis requires more time travelling to a dialysis centre and is less flexible, but gives
superior electrolyte control.

Assessment of dialysis patients:

- Weight-patients know their dry weight
- Potassium and ECG changes associated with hyperkalaemia
- Pulmonary oedema and hypertension.