ADULT POLYCYSTIC KIDNEY DISEASE

Autosomal dominant (adult) polycystic kidney disease (ADPKD)
Definition
Autosomal dominant inherited disorder leading to the development of multiple expanding renal parenchymal cysts.

Epidemiology
Incidence is 0.1%; 95% are bilateral. Symptoms manifest in the 4th decade. ADPKD accounts for 10% of all cases of renal failure.

Pathology
The kidneys reach an enormous size due to multiple fluid-filled cysts and can easily be palpated on abdominal examination. Expansion of the cysts results in ischaemic atrophy of the surrounding renal parenchyma, and obstruction of normal renal tubules. End-stage renal failure is inevitable and occurs around the age of 50 yrs.

Associated disorders
10 - 30% incidence of Circle of Willis berry aneurysms (associated with subarachnoid haemorrhage); cysts of the liver (33%), pancreas (10%), and spleen (<5%); renal adenoma; cardiac valve abnormalities; aortic aneurysms and diverticular disease.

Aetiology
PKD-1 gene defects (chromosome 16) account for 90% of cases; PKD-2 gene defects (chromosome 4) cause 10%, and now a third gene, PKD-3 is also implicated. Pathogenesis theories include intrinsic basement membrane abnormalities; tubular epithelial hyperplasia (causing tubular obstruction and basement membrane weakness), and alterations in the supportive extracellular matrix due to defective proteins, all of which may cause cyst formation.

Presentation
Positive family history (50% inheritance); palpable abdominal masses; flank pain (due to mass effect, infection, stones, or following acute cystic distension due to haemorrhage or obstruction); macroscopic (and microscopic) haematuria; UTI; and hypertension (75%). Renal failure may present with lethargy, nausea, vomiting, anaemia, confusion, and seizures.

Differential diagnosis
Renal tumours; simple cysts; von Hippel - Landau syndrome (cerebellar and retinal haemangioblastomas; renal, adrenal, and pancreatic cysts); tuberous sclerosis (adenoma sebaceum, epilepsy, learning difficulties, with polycystic kidneys and renal tumours).

Investigation
This depends on the presenting symptoms.
- For suspected UTI culture urine.
- For haematuria urine cytology, flexible cystoscopy, and renal ultrasound. On ultrasound the kidneys are small and hyperechoic, with multiple cysts of varying size, many of which show calcification. If the nature of the cysts cannot be determined with certainty on ultrasound, arrange a renal CT.
- Renal failure will be managed by a nephrologist. Anaemia may occur, though ADPKD may cause increased erythropoietin production and polycythaemia.
- Renal imaging (ultrasound and CT are useful for investigation of complications).

Treatment
The aim is to preserve renal function as long as possible (control hypertension and UTI). Infected cysts (abscesses) should be drained. Persistent, heavy haematuria can be controlled by embolisation or nephrectomy. Progressive renal failure requires dialysis and, ultimately, renal transplantation.