Adult polycystic kidney disease - Renal cystic disease

Renal cystic disease

Adult polycystic kidney disease

Definition

Adult polycystic kidney disease is an autosomal dominant inherited condition characterised by gradual replacement of renal and occasionally other tissue by cysts.

Incidence/prevalence

1 in 1000. Accounts for 10% of chronic renal failure cases.

Age

Presents at any age.

Sex

M = F

Aetiology

Autosomal dominant; 90% of cases associated with PKD1 gene on chromosome 16, and 5–10% of cases with PKD2 on chromosome 4. PKD1 patients tend to develop renal failure earlier.

PKD1 encodes a protein called polycystin-1, which is found in plasma membranes of renal tubular epithelial cells, hepatic bile duct cells and pancreatic duct cells. Renal, liver and pancreatic cysts all occur in APKD. Abnormal polycystin-1 protein may affect cell adhesion, leading to inappropriate cell growth. This gene is closely related to the tuberous sclerosis gene in which renal cysts can also occur.

PKD2 encodes polycystin-2 protein, which is expressed in the distal tubules, collecting duct and thick ascending limb of Henle and appears to be involved in calcium signalling.

The mechanism of cyst formation is not yet under-stood, although it appears that there may need to be a second somatic mutation, because the disease variably affects tubules and individuals. There is evidence that the cysts arise from one progenitor cell (monoclonal). There also appear to be environmental effects, for example liver cysts are more common in women, which is thought to be an effect of oestrogen.

Pathophysiology

Cysts develop in both kidneys, progressing in size and number over the years. They gradually compress the renal parenchyma. There is also evidence of vascular disease and interstitial fibrosis leading to gradual deterioration of renal function.

Clinical features

Around two thirds of patients have a positive family history and the disease may be detected due to radiological screening of family members. Patients may present with loin pain, lumbar pain, haematuria, an abdominal mass, hypertension or with chronic renal impairment. Pyelonephritis, an infected cyst or bleeding into cysts may occur, causing acute abdominal or lumbar pain and haematuria in some cases.

On examination, bilateral, irregular abdominal masses may be palpable. The liver may also be enlarged.

Macroscopy

Bilateral kidney enlargement with a mass of cysts ranging in diameter.

Complications

Cysts develop in the liver in 40%, also in the lung and pancreas. There is an association with berry aneurysms (10–30%) of the cerebral arteries, which together with hypertension, predisposes to subarachnoid haemorrhage (SAH). The risk of SAH may be as high as 20% in those with a positive family history of SAH.

Unlike other causes of renal failure, in APKD erythropoietin levels are often preserved, preventing the development of anaemia. In some cases polycythaemia may occur.

There is also an association with heart valve disease, diverticulosis and abdominal/inguinal hernias. Renal stones may develop.

There does not appear to be an increased risk of renal cell carcinoma, although the diagnosis of this is made harder by the presence of multiple cysts.

Investigations

Diagnosis is confirmed by renal ultrasound or IVU, which shows large kidneys with long ‘spidery’ calyces. In children and young adults, the diagnosis may be missed as the cysts develop with age. In older people without APKD, simple cysts may occur, so over the age of 60, four or more cysts in each kidney are needed to make the diagnosis. Genetic diagnosis is difficult because of multiple large genes with a diffuse spread of mutations.

Management

Supportive. Control of infection with antibiotics and treat hypertension.

Development of end stage renal failure means that dialysis or transplantation are needed.

Some patients require cyst decompression for intractable pain, or even nephrectomy if very enlarged kidneys cause symptoms such as tiredness and loss of appetite.

Screen family members and offer genetic counselling as appropriate.

Prognosis

Approximately 25% of patients need dialysis by the age of 50, 40% by age 60 and 50–75% by age 75. One third die from complications of hypertension, particularly heart disease and stroke. Poor prognostic indicators include younger age at diagnosis, Afro Caribbeans, males, hypertension, PKD1 gene and an episode of macroscopic haematuria.