New insights into the molecular pathophysiology of polycystic kidney disease

Polycystic kidney diseases are characterized by the progressive expansion o f multiple cystic lesions, which compromise the function of normal parenchy ma. Throughout the course of these diseases, renal tubular function and str ucture are altered, changing the tubular microenvironment and ultimately ca using the formation and progressive expansion of cyctic lesions. Renal tubu les are predisposed to cystogenesis when a germ line mutation is inherited in either the human PKD1 or PKD2 genes in autosomal dominant polycystic kid ney disease (ADPKD) or when a homozygous mutation in Tg737 is inherited in the orpk mouse model of autosomal recessive polycystic kidney disease (ARPK D). Recent information strongly suggests that the protein products of these disease genes may form a macromolecular signaling structure, the polycysti n complex, which regulates fundamental aspects of renal epithelial developm ent and cell biology. Here, we re-examine the cellular pathophysiology of r enal cyst formation and enlargement in the context of our current understan ding of the molecular genetics of ADPKD and ARPKD.