This patient gives a history of intermittent haematuria; obtain a brief' history and examine this patient's abdomen.



· 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



· Arteriovenous fistulas in the arms or subclavian dialysis catheter (remember that in the UK polycystic kidneys constitute the

third most common cause for chronic renal failure after glomerulonephritis and pyelonephritis).

· Palpable kidneys (confirm by bimanual palpation and ballottement; there is a resonant note on percussion due to overlying

colon; the hand can get between the swelling and the costal margin).

Proceed as follows:

· Look for the following signs:

-Enlarged liver due to cystic disease.

-Transplanted kidney may be palpable in either iliac fossa.

-Third nerve palsy (berry aneurysms are associated with polycystic kidneys). -Look for anaemia (due to chronic renal failure) or

polycythaemia (due to

increased erythropoiesis).

- Check the blood pressure (hypertension develops in 75% of cases).

· Tell the examiner that you would like to investigate as follows:

-Look at the ECG for left ventricular hypertrophy (it appears that LVH occurs to a greater degree for a given rise in blood pressure in

ADPKD compared with other renal disorders and with essential hypertension).

- Microscopic haematuria.

Remember. Polycystic kidney disease is a misnomer as it is a systemic disorder affecting many organs.


This patient has polycystic kidney disease (lesion and diagnosis) and is currently on dialysis as evidenced by the arteriovenous

fistula in the arm functional status).

Read: N Engl J Med 1993; 329: 332.


How may polycystic disease present?

Haematuria, hypertension, urinary tract infection, pain m the lumbar region, uraemic symptoms, subarachnoid haemorrhage

associated with berry aneurysm, and complications of associated liver cysts.

Is the kidney involvement usually unilateral or bilateral?

The disease is universally bilateral; unilateral cases reported probably represent multicystic renal dysplasia.


What do you know about the prevalence of this disease?

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common hereditary disorders, being 10 times more

common than sickle cell disease, 15 times more common than cystic fibrosis and 20 times more common than Huntington's disease.

It has a worldwide distribution. In the white population the disease appears to occur in about 1 in 400 to 1 in 1000 people (Acta Med

Scand 1957; 328: 1-255). 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 (Kidney lnt

1992; 41:1311-19).

In which other conditions may bilateral renal cysts be observed in an ultrasonographic study?

Multiple simple cysts, autosomal recessive polycystic kidney disease in children, tuberous sclerosis and von Hippel-Lindau


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 than 30 years may be regarded as

sufficient to establish a diagnosis; among those aged 30-59 years the presence of at least two cysts in each kidney; and among

those aged 60 years and above at least four cysts in each kidney should be required (Lancet 1994; 343: 824-7).

How would you like to manage this patient?

· FBC, urea and electrolytes, serum creatinine, urine microscopy, urine culture.

· Ultrasonography of the kidneys to confirm the diagnosis. Ultrasound may be equivocal in subjects under the age of 20 years.

· Contrast-enhanced spiral CT head scan or MRI as a screening test for intracranial aneurysms in patients aged 18-40 years and

with a family history of intracranial aneurysms or subarachnoid haemorrhage (N Engl J Med 1992; 327: 953-5).

In which other organs are cysts seen in this condition?

Liver (in 30% of cases), spleen, pancreas, lungs, ovaries, testes, epididymis, thyroid, uterus, broad ligament and bladder.

What are the neurological manifestations of this condition?

Subarachnoid haemorrhage from an intracranial berry aneurysm, causing death or neurological lesions in about 9% of patients.

About 8% of patients with ADPKD have an asymptomatic intracranial aneurysm; the prevalence is twice as high in those with a

family history of such aneurysms or of subarachnoid haemorrhage.

What is the pathology?

Cysts develop in Bowman's capsule and at other levels in the nephron, displacing kidney tissue.

What cardiovascular manifestations have been reported in these patients?

· Mitral valve prolapse in 26%.

· Other lesions commonly seen are mitral, aortic and tricuspid valve regurgitation.

What are the renal manifestations of this disease?

· The main structural change is the formation of cysts. Cysts enlarge, lose their tubular connection and become isolated from the

glomerulus, requiring trans-epithelial transport of solutes and fluids for further expansion. Cyst fluids have different

compositions, some having high and others low sodium concentration.

· One of the earliest and most consistent functional abnormalities is a decrease in renal concentrating ability.

· There may be altered endocrine function as reflected by increased secretion of both renin (causing increased predilection to

hypertension) and erythropoietin (resulting in better maintained haematocrit in renal failure, unlike in renal failure due to other

causes: rarely can result in polycythaemia).

What are the causes of abdominal pain in this disease?

Infected cyst, haemorrhage into cyst or diverticular perforation.

What are the complications of polycystic kidney disease?

Renal complications

· Hypertension (intrarenal activation of the renin-angiotensin system is said to be the main mechanism and hence ACE inhibitors

are first line agents to control blood pressure).

· Pain back pain or abdominal pain. (Cyst decompression may help to relieve pain but does not alter the rate of progression.)

· Gross or microscopic haematuria.

· Cyst infection (lipophilic antibiotics against Gram-negative bacteria such as cotrimoxazole, fluoroquinolones penetrate the cysts

better and are preferred to standard antibacterial agents).

· Renal calculi (seen in 10-20% of patients with ADPKD; are frequently radiolucent and composed of uric acid)

· Urinary tract infection including pyelonephritis.

· Proteinuria.

· Renal failure (once the GFR falls below 50 mi/minute the rate of progression is more rapid than in other primary renal disorders

and is about 5 mi/minute every year). About one half of the patients have normal life with adequate renal function.

Extrarenal manifestations

· Cystic: cysts in the liver, ovary, pancreas, spleen and central nervous system. Unlike renal cyst formation, liver cysts seem to

be influenced by female hor-mones. Whilst men and women have the same frequency of liver cysts, massive liver cysts are

almost exclusively found in women.

· Non-cystic:

-Cardiac valvular abnormalities mitral valve prolapse (seen in -20% of

patients with ADPKD), aortic valve abnormalities.

-Intracranial saccular aneurysm or berry aneurysm. Magnetic resonance angio-graphy is the most reliable technique of non-invasive

screening among such patients.

· Gastrointestinal - colonic diverticula, hernias of the anterior abdominal wall.

What do you know about the genetic transmission of this disease?

Polycystic kidney disease is an autosomal dominant disorder. Mutations in at least three different genes can lead to autosomal

dominant polycystic kidney disease (ADPKD). The PKD1 gene is located on chromosome 16 (Cell 1994; 77: 8814). The protein

product of PKD1, polycystin-l, is an integral membrane glycoprotein involved in cell-to-cell and/or cell-to-matrix interaction (J Am Soc

Nephrol 1995: 6:1125-33). The PKD2 gene is situated on chromosome 4 and its protein product is similar to the alphal subunit of

voltage-activated calcium and sodium channels, suggesting a related role for polycystin-2 (Science 1996; 272: 133942). The

poly-cystins interact through their C-terminal cytoplasmic tails which suggests that PKDIand PKD2 may function through a common

signalling pathway (Nat Genet 1997; 16: 179-83). At least one other gene containing mutations that lead to ADPKD is known to exist;

its chromosomal location is not known.

Among the European ADPKD population, PKD1is the cause in about 85% of families and PKD2 the cause in about 15%.

Compared with individuals affected by PKD2, those with PKDI have more severe disease with a higher prevalence of hypertension,

an increased risk of progression into renal failure and shorter life expectancy. Although PKD2is clinically milder than PKDI it has a

deleterious impact on overall life expectancy and cannot be regarded as a benign disorder (Lancet 1999: 353: 103-7).

What do you know about screening in this condition?

· The children and siblings of patients with established ADPKD should be offered screening.

· Affected individuals should have their blood pressure checked regularly and offered genetic counselling.

· Genetic linkage analysis can be utilized in many families. Ultrasound is usually not useful before the age of 20 years.

What are the poor prognostic factors in ADPKD?

Patients are liable to progress more rapidly if they are male, or have polycystin-I mutations, early onset hypertension, episodes of

gross haematuria (J Am Soc

Nephrol 1997; 8: 1560-7), or family history of hypertension in the unaffected patient (JAm Soc Nephrol 1995; 6: 1643-8), 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 com-plications of hypertension (including heart disease,

intracerebral haemorrhage and rupture of berry aneurysm). The remaining third die from unrelated causes.

Sir W. Bowman (1816-1892), Surgeon at the Royal London Ophthalmic Hospital.

E.L. Potter (1901-),US pathologist. She also described Potter's syndrome with renal agenesis and characteristic of epicanthic folds,

receding jaw and Iow set ears with less cartilage than usual.

O.Z. Dalgaard's study in 1957 clarified the autosomal dominant pattern of inheritance of the disease.