Autosomal dominant polycystic kidney disease (ADPKD) is responsible for up to 10% of prevalent patients with end-stage renal disease (ESRD). It is characterized by the enlargement of multiple bilateral renal cysts, present in almost all patients by their fifth decade. Loin pain is a common symptom that may be caused by cyst growth, intracyst haemorrhage, nephrolithiasis, or infection. Gross haematuria is also a common feature, but usually settles spontaneously. Excretory impairment develops after extensive cystic change has occurred and progresses to ESRD in half of all affected patients by the age of 60. However, the onset of cystic change and rate of renal functional decline are highly variable between individuals. ADPKD associated with the PKD1 gene has an earlier average age of cyst development and ESRD than PKD2, but the two cannot be distinguished on clinical grounds. Polycystins 1 and 2 are expressed in various organs and extrarenal disease may be the presenting feature. Intracranial aneurysms are five times more common in patients with ADPKD, but rupture is infrequent. Liver cysts are present in most patients and may be complicated by haemorrhage or infection, though liver failure is very rare. Massive hepatic cystic disease is confined to women, reflecting stimulatory effects of oestrogen on hepatic cyst growth. Cardiovascular disease is the leading cause of death in ADPKD and vascular dysfunction is present in many patients even before the development of excretory impairment. However, despite the multisystem manifestations of ADPKD, survival from ESRD is better for patients with ADPKD than for other non-diabetic causes of kidney failure.
A study of sirolimus and mTOR kinase inhibitor in a hypomorphic Pkd1 mouse model of autosomal dominant polycystic kidney disease
