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Molecular pathogenesis of autosomal dominant polycystic kidney disease

Published online by Cambridge University Press:  17 January 2006

Bradley K. Yoder
Affiliation:
University of Alabama at Birmingham, Department of Cell Biology, 1918 University Blvd MCLM652, Birmingham, AL 35294, USA.
Sharon Mulroy
Affiliation:
Department of Medical Genetics, Cambridge Institute of Medical Research, Addenbrooke's Hospital, Cambridge, CB2 2XY, UK.
Hannah Eustace
Affiliation:
Department of Medical Genetics, Cambridge Institute of Medical Research, Addenbrooke's Hospital, Cambridge, CB2 2XY, UK.
Catherine Boucher
Affiliation:
Department of Medical Genetics, Cambridge Institute of Medical Research, Addenbrooke's Hospital, Cambridge, CB2 2XY, UK.
Richard Sandford
Affiliation:
Department of Medical Genetics, Cambridge Institute of Medical Research, Addenbrooke's Hospital, Cambridge, CB2 2XY, UK.

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is one of the commonest inherited human disorders yet remains relatively unknown to the wider medical, scientific and public audience. ADPKD is characterised by the development of bilateral enlarged kidneys containing multiple fluid-filled cysts and is a leading cause of end-stage renal failure (ESRF). ADPKD is caused by mutations in two genes: PKD1 and PKD2. The protein products of the PKD genes, polycystin-1 and polycystin-2, form a calcium-regulated, calcium-permeable ion channel. The polycystin complex is implicated in regulation of the cell cycle via multiple signal transduction pathways as well as the mechanosensory function of the renal primary cilium, an enigmatic cellular organelle whose role in normal physiology is still poorly understood. Defects in cilial function are now documented in several other human diseases including autosomal recessive polycystic kidney disease, nephronophthisis, Bardet–Biedl syndrome and many animal models of polycystic kidney disease. Therapeutic trials in these animal models of polycystic kidney disease have identified several promising drugs that ameliorate disease severity. However, elucidation of the function of the polycystins and the primary cilium will have a major impact on our understanding of renal cystic diseases and will create exciting new opportunities for the design of disease-specific therapies.

Type
Review Article
Copyright
Cambridge University Press 2006

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