title: Variable Cyst Development in Autosomal Dominant Polycystic Kidney Disease: The Biologic Context.
abstract: Patients with autosomal dominant polycystic kidney disease (ADPKD) typically carry a mutation in either the PKD1 or PKD2 gene, which leads to massive cyst formation in both kidneys. However, the large intrafamilial variation in the progression rate of ADPKD suggests involvement of additional factors other than the type of mutation. The identification of these factors will increase our understanding of ADPKD and could ultimately help in the development of a clinically relevant therapy. Our review addresses the mechanisms by which various biologic processes influence cyst formation and cyst growth, thereby explaining an important part of the inter- and intrafamilial variability in ADPKD. Numerous studies from many laboratories provide compelling evidence for the influence on cyst formation by spatiotemporal gene inactivation, the genetic context, the metabolic status, the presence of existing cysts, and whether the kidneys were challenged by renal injury. Collectively, a solid basis is provided for the concept that the probability of cyst formation is determined by functional PKD protein levels and the biologic context. We model these findings in a graphic representation called the cystic probability landscape, providing a robust conceptual understanding of why cells sometimes do or do not form cysts.
authors: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors: Wouter N
authors: WN
authors: Leonhard
authors: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors: Hester
authors: H
authors: Happe
authors: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands d.j.m.peters@lumc.nl.
authors: Dorien J M
authors: DJ
authors: Peters
mesh_terms: D001686:Biological Phenomena; D006801:Humans; D016891:Polycystic Kidney, Autosomal Dominant / Q000209:etiology* / Q000235:genetics; D011336:Probability; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase
chemical_list: D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D017346:Protein Serine-Threonine Kinases
keywords: ADPKD; Biological Context; PKD1; Polycystin; Probability Landscape; polycystic kidney disease