Autosomal dominant polycystic kidney disease

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					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,
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