Fluid transport and cystogenesis in autosomal dominant polycystic kidney disease.
Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent inherited nephropathy. The development and enlargement of cysts in ADPKD requires tubular cell proliferation, abnormalities in the extracellular matrix and transepithelial fluid secretion. Multiple studies have suggested that fluid secretion across ADPKD cyst-lining cells is driven by the transepithelial secretion of chloride, mediated by the apical CFTR channel and specific basolateral transporters. The whole secretory process is stimulated by increased levels of cAMP in the cells, probably reflecting modifications in the intracellular calcium homeostasis and abnormal stimulation of the vasopressin V2 receptor. This review will focus on the pathophysiology of fluid secretion in ADPKD cysts, starting with classic, morphological and physiological studies that were followed by investigations of the molecular mechanisms involved and therapeutic trials targeting these pathways in cellular and animal models and ADPKD patients. This article is part of a Special Issue entitled: Polycystic Kidney Disease.
Division of Nephrology, Université catholique de Louvain Medical School, B-1200, Brussels, Belgium.
Sara
S
Terryn
Anh
A
Ho
Renaud
R
Beauwens
Olivier
O
Devuyst
D000818:Animals; D020346:Aquaporins / Q000502:physiology; D001693:Biological Transport, Active; D002712:Chlorides / Q000378:metabolism; D000242:Cyclic AMP / Q000502:physiology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000502:physiology; D055724:Electrophysiological Phenomena; D004848:Epithelium / Q000503:physiopathology; D045604:Extracellular Fluid / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D016891:Polycystic Kidney, Autosomal Dominant / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D015398:Signal Transduction; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology; D050396:TRPP Cation Channels / Q000502:physiology; D014667:Vasopressins / Q000502:physiology; D014882:Water-Electrolyte Balance
D020346:Aquaporins; D002712:Chlorides; D050396:TRPP Cation Channels; D014667:Vasopressins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000242:Cyclic AMP; D000254:Sodium-Potassium-Exchanging ATPase