Autosomal dominant polycystic kidney disease: modifier genes and endothelial dysfunction.

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the development of multiple cysts in both kidneys, causing progressive renal failure. By the age of 60 years, about half the patients with ADPKD have end-stage renal disease (ESRD). In Europe and North America, ADPKD is responsible for 5–10% of the patients requiring renal replacement therapy [1]. ADPKD is also characterized by extrarenal manifestations (e.g. intracranial aneurysms or liver cysts) and hypertension. The latter occurs in 50–70% of patients, even before any reduction in renal function [1]. Mutations in two genes, PKD1 and PKD2, are responsible for 85% and 15% of ADPKD cases, respectively. The proteins encoded by PKD1 (polycystin-1) and PKD2 (polycystin-2) interact in the plasma membrane to participate in signalling pathways that regulate renal tubular cell maturation [2]. In this comment, we will discuss the role and potential implications of disease-modifying genes in ADPKD.