CME.Ong.qxd 5/21/09 4:55 PM Page 278 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 childhood with significant morbidity. By Massive polycystic kidneys 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 2 with a prevalence of 1:400 to 1:1,000 live of cases). 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 Non-renal: liver and pancreatic occur more frequently and severely in Genetics and pathophysiology • enlargement or infection. females, correlating with oestrogen Inheritance of ADPKD is autosomal exposure (eg pregnancy, contraceptive 4 dominant with 100% disease pene- Hypertension pill). 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. • PKD2 (chromosome 4q21), 10–15% Intracerebral aneurysms of cases, encodes for the polycystin-2 Cyst haemorrhage and haematuria Intracerebral aneurysms (ICA) occur in protein. Gross haematuria occurs in 30–50% of 6% of ADPKD patients without a family A small number of families unlinked ADPKD patients, with rising incidence history of ICA and in 16% of patients 6 to either gene could indicate the poten- as kidney size increases. It usually occurs with a positive family history of ICA. 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, trauma, stones, infec- ical event in ADPKD is hypertensive similar clinical phenotype, but PKD2 tion or tumour. haemorrhage or ischaemic stroke. patients have a more favourable course. The mean age of onset of end-stage renal Nephrolithiasis Symptoms of chronic kidney disease failure (ESRF) is 53 years for PKD1 and 69 years for PKD2. Unlike PKD1, women Nephrolithiasis occurs in 20–30% of Lethargy, poor appetite, reduced urine with PKD2 have a later onset of ESRF patients. The presence of renal calculi volume, fluid retention etc are all symp- than men. should be considered if acute pain, acute toms of chronic kidney disease (CKD). 278 © Royal College of Physicians, 2009. All rights reserved. CME.Ong.qxd 5/21/09 4:55 PM Page 279 CME Renal medicine Pancreatic cysts Investigation viduals have recently been reported (Table 2).8 The previously used criteria Although pancreatic cysts occur in Table 2 lists the investigations used in had a sensitivity of 100% in PKD1 patients 9% of patients older than 20 years, assessing ADPKD patients. aged 30 years or older but false-negative this is not related to pancreatic New unified diagnostic ultrasound rates for PKD2 (23%) and PKD1 (5%) in dysfunction.7 criteria for at-risk PKD1 and PKD2 indi- younger patients. Where the family history is unknown or negative, these new criteria Table 1. Renal cystic diseases. may not apply and mutation analysis may be indicated for either disease exclusion or Genetic Non-genetic diagnostic purposes.8,9 Clinically, the pres- ence of bilateral enlarged cystic kidneys Autosomal dominant: Acquired: with hepatic cysts and absence of positive • ADPKD • Simple cysts extrarenal manifestations (suggesting an • Tuberous sclerosis • Acquired renal cystic disease • Von Hippel-Lindau disease • Hypokalaemia-related cysts alternative cystic disease) make the diag- • Medullary cystic disease nosis highly probable. • RCAD The Consortium for Radiologic Autosomal recessive: Developmental: Imaging Studies of PKD (CRISP) suggests • ARPKD • Medullary sponge kidney that the rate of disease progression can be • Juvenile-onset nephronophthisis • Multicystic dysplastic kidneys monitored through serial MRI kidney • Other rare syndromes associated • Pyelocalyceal cysts volume measurements prior to significant with multiple malformationse decline in glomerular filtration rate.10 X-linked: • Oral-facial-digital syndrome type 1 Management Chromosomal disorders: There is no cure for ADPKD. Treatment is • Trisomy 21 • Trisomy 13 aimed at blood pressure control, prompt • Trisomy 18 treatment of infections and disease com- • Trisomy C plications, and the management of CKD. ADPKD ϭ autosomal dominant polycystic kidney disease; ARPKD ϭ autosomal recessive polycystic kidney disease; RCAD ϭ renal cysts and diabetes syndrome. Pain Pain should be treated with simple anal- gesia. Lifestyle modification and avoidance of aggravating activities can also be useful.3 Patients may require pain clinic referral and surgical management (cyst decompression, renal denervation or nephrectomy). Hypertension The aim is to achieve a blood pressure below 130/80 mmHg.15 There is no spe- cific evidence that any particular antihyper- tensive drug is more effective in ADPKD. A trial currently in progress, Halt Progression in PKD (HALT-PKD), is investigating whether the use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers confers additional benefit. Urinary tract infection Urine cultures may be persistently negative in cyst infection. Ureteric obstruction from Fig 1. End-stage autosomal dominant polycystic kidneys. stone or clot with associated infection © Royal College of Physicians, 2009. All rights reserved. 279 CME.Ong.qxd 5/21/09 4:55 PM Page 280 CME Renal medicine should be excluded. Patients will require presence of recurrent infection, it would be therapy for cyst haemorrhage and haema- prompt antibiotic treatment adjusted to prudent to consider long-term prophy- turia as bleeding is normally self-limiting renal function and culture results. Cyst lactic antibiotics.15 and resolves within days.15 Further inves- infection requires antibiotics that penetrate tigation to exclude malignancy may be the cyst (eg macrolides, ciprofloxacin, Cyst haemorrhage and haematuria considered if episodes are frequent and/or trimethoprim etc). A prolonged course of prolonged (especially in patients over antibiotics may be required. Surgical inter- Conservative management with bed rest, 50 years old) or if other systemic symp- vention is occasionally indicated. In the hydration and analgesia is the mainstay of toms are present. Rarely, haemodynami- cally significant bleeding can occur, requiring hospital admission, transfusion and computed tomography with or without angiography. Persistent haemor- rhage may require segmental arterial embolisation (coils) or nephrectomy. Nephrolithiasis Renal stones normally resolve with con- servative measures: hydration, treatment of infection and analgesia. More compli- cated cases should be referred for extra- corporeal shockwave lithotripsy and percutaneous nephrostolithotomy.3 Massive polycystic kidneys and large renal cysts Cyst reduction by alcohol sclerosis, percutaneous drainage or laparoscopic deroofing are options. Laparoscopic renal denervation can be considered in rare Fig 2. Ultrasound scan showing multiple cysts within the kidney. cases of uncontrolled pain.3 Nephrectomy Key Points Autosomal dominant polycystic kidney disease is a common genetic disease due to mutations in two genes, PKD1 and PKD2 Patients may present with or develop significant extrarenal manifestations The main aim of therapy