title: Autosomal Dominant Polycystic Kidney Disease: A Path Forward.
abstract: Autosomal dominant polycystic kidney disease (ADPKD) is the commonest inherited cause of renal failure in adults, and is due to loss-of-function mutations in either the PKD1 or PKD2 genes, which encode polycystin-1 and polycystin-2, respectively. These proteins have an essential role in maintaining the geometric structure of the distal collecting duct in the kidney in adult life, and their dysfunction predisposes to renal cyst formation. The typical renal phenotype of ADPKD is the insidious development of hundreds of renal cysts, which form in childhood and grow progressively through life, causing end-stage kidney failure in the fifth decade in about half affected by the mutation. Over the past 2 decades, major advances in genetics and disease pathogenesis have led to well-conducted randomized controlled trials, and observational studies that have resulted in an accumulation of evidence-based data, and raise hope that the lifetime risk of kidney failure due to ADPKD will be progressively curtailed during this century. This review will provide a contemporary summary of the current state of the field in disease pathogenesis and therapeutics, and also briefly highlights the importance of clinical practice guidelines, patient perspectives, patient-reported outcomes, uniform trial reporting, and health-economics in ADPKD.
authors.affiliation: Department of Renal Medicine, Westmead Hospital, Western Sydney Local Health District, Westmead, Sydney, Australia; Centre for Transplant and Renal Research, Westmead Institute for Medical Research, University of Sydney, Westmead, Sydney, Australia. Electronic address: g.rangan@sydney.edu.au.
authors.forename: Gopala K
authors.initials: GK
authors.lastname: Rangan
authors.affiliation: Sydney School of Public Health, The University of Sydney, Sydney, Australia; Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, Australia.
authors.forename: Pamela
authors.initials: P
authors.lastname: Lopez-Vargas
authors.affiliation: Department of Renal Medicine, Westmead Hospital, Western Sydney Local Health District, Westmead, Sydney, Australia; Centre for Transplant and Renal Research, Westmead Institute for Medical Research, University of Sydney, Westmead, Sydney, Australia.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Nankivell
authors.affiliation: Department of Genetic Medicine, Westmead Hospital, Western Sydney Local Health District, Sydney, Australia.
authors.forename: Michel
authors.initials: M
authors.lastname: Tchan
authors.affiliation: Sydney School of Public Health, The University of Sydney, Sydney, Australia; Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, Australia.
authors.forename: Allison
authors.initials: A
authors.lastname: Tong
authors.affiliation: Sydney School of Public Health, The University of Sydney, Sydney, Australia; Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, Australia.
authors.forename: David J
authors.initials: DJ
authors.lastname: Tunnicliffe
authors.affiliation: The University of Melbourne, Department of Medicine, Melbourne Health and Northern Health, Melbourne, Australia; Department of Nephrology, The Royal Melbourne Hospital, Parkville, Victoria, Australia.
authors.forename: Judy
authors.initials: J
authors.lastname: Savige
mesh_terms: D017668:Age of Onset; D006801:Humans; D016891:Polycystic Kidney, Autosomal Dominant / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*; D017410:Practice Guidelines as Topic; D051437:Renal Insufficiency / Q000209:etiology; D015398:Signal Transduction; D050396:TRPP Cation Channels / Q000737:chemistry / Q000378:metabolism*; D014667:Vasopressins / Q000378:metabolism
chemical_list: D050396:TRPP Cation Channels; D014667:Vasopressins
keywords: Autosomal dominant polycystic kidney disease; clinical trials; therapy