CME Renal medicine Clinical Medicine 2009, Vol 9, No 3: 278–83
Natural history deterioration in renal function and
Autosomal dominant haematuria are present.
Patients are usually asymptomatic until
polycystic kidney the middle decades, but 2–5% present in
Massive polycystic kidneys
childhood with significant morbidity. By
disease the age of 60, 50% of patients with and large renal cysts
ADPKD will require renal replacement Abdominal discomfort or pain can be
therapy. Poor prognostic indicators for caused by massive cysts. Renal cysts are
Chern Li Chow, Specialist Registrar and renal survival include male sex, black not unique to ADPKD. Other potential
Honorary Research Fellow in Nephrology; race, haematuria before age 30, multiple causes are given in Table 1.
Albert CM Ong, Professor of Renal Medicine pregnancies, hypertension before age 35,
Academic Unit of Nephrology, School of proteinuria, renal size and PKD1 muta-
Medicine, University of Sheffield tion. ADPKD patients do not have a Cancer
higher risk of mortality than other There is no evidence for an increased risk
Autosomal dominant polycystic kidney patients with ESRF. The main cause of of renal cell carcinoma in the ADPKD
disease (ADPKD) is an inherited disease mortality is cardiovascular disease (36% population, but haematuria and flank
with a prevalence of 1:400 to 1:1,000 live of cases).2 pain with anorexia and weight loss
births.1 It is the most common genetic should prompt further investigation.
cause of renal failure, accounting for Clinical features
10% of patients on dialysis. ADPKD is a Pain Liver cysts
systemic disorder characterised by pro-
gressive kidney enlargement, cyst for- • Renal: acute pain due to infection, Hepatic cysts are the most common
mation in other organs (liver, pancreas) stones, intracystic haemorrhage and extrarenal manifestation, increasing
and non-cystic complications (arterial urinary tract obstruction; chronic with older age (58% in the third decade
aneurysm). pain due to pressure, stretching of the and 94% in the fourth decade on mag-
renal capsule or structural distortion. netic resonance imaging (MRI).3 They
Genetics and pathophysiology • Non-renal: liver and pancreatic occur more frequently and severely in
enlargement or infection. females, correlating with oestrogen
Inheritance of ADPKD is autosomal exposure (eg pregnancy, contraceptive
dominant with 100% disease pene- Hypertension pill).4 They are usually asymptomatic
trance. Each offspring has a 50% and do not lead to hepatic failure. Pain
chance of inheriting the disease. There Hypertension is a common early finding – from compression, feeling of satiety,
is a 5% rate of new mutation. in 60% of patients with normal renal cystic haemorrhage and infection are the
Mutations in either of two genes function. most common symptoms. Rarely, massive
coding for membrane proteins can lead polycystic liver disease (female prepon-
to ADPKD:1 Urinary tract infection derance) can result in portal hyperten-
sion.3 Rare cases of congenital hepatic
• PKD1 (chromosome 1613.3), 85–90% About 30–50% of patients will have an fibrosis have also been described.5
of cases, encodes for the polycystin-1 episode of urinary tract infection in their
protein lifetime.
Intracerebral aneurysms
• PKD2 (chromosome 4q21), 10–15%
of cases, encodes for the polycystin-2 Cyst haemorrhage and haematuria Intracerebral aneurysms (ICA) occur in
protein. 6% of ADPKD patients without a family
Gross haematuria occurs in 30–50% of
A small number of families unlinked ADPKD patients, with rising incidence history of ICA and in 16% of patients
to either gene could indicate the poten- as kidney size increases. It usually occurs with a positive family history of ICA.6
tial existence of a third gene (PKD3). spontaneously but may be related to However, the most common neurolog-
PKD1 and PKD2 gene mutations have physical activity,