Polycystic kidney disease: the cilium as a common pathway in cystogenesis.

Abstract

Polycystic kidney disease (PKD) is characterized by the formation and progressive expansion of cysts in the kidney, frequently leading to renal failure. The purpose of this review is to summarize recent studies that have provided insight into the mechanisms of cytogenesis. Mutations in cilia-associated proteins have been identified in a number of diseases associated with cyst formation, including autosomal dominant and recessive PKD, and nephronophthisis. The primary cilia are finger-like projections on the surface of all kidney cells, except acid-base transporting intercalated cells in the collecting duct. Cilia have been proposed to serve as mechano- or chemosensors, responding to and interacting with the microenvironment. Abnormal cilia structure or function or both may lead to abnormalities in cell proliferation and tubular differentiation, ultimately leading to cyst formation. In addition to ciliary dysfunction, other potential mechanisms of cystogenesis need to be explored. Our understanding of the importance of the primary cilium in renal cyst formation may guide potential therapy for cystic kidney diseases by targeting the structural and functional integrity of the cilia.