Long-term trajectory of kidney function in autosomal-dominant polycystic kidney disease

• Type of Material: Article
• Authors: Alan S. L. Yu, University of Kansas; Chengli Shen, University of Pittsburgh; Douglas P. Landsittel, University of Pittsburgh; Jared J. Grantham, University of Kansas; Larry T. Cook, University of Kansas; Vicente E. Torres, Mayo Clinic; Arlene Chapman, Emory University; Kyongtae Ty Bae, University of Pittsburgh; Michal Mrug, University of Alabama Birmingham; Peter C. Harris, Mayo Clinic; Frederic Rahbari Oskoui, Emory University; Tiange Shi, University of Pittsburgh; William M. Bennett, Legacy Good Samaritan Hospital
• Language: English
• Date: 2019-05-01
• Publisher: Elsevier Science Inc.
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.kint.2018.12.023
• Title of Journal or Parent Work: Kidney International
• Volume: 95
• Issue: 5
• Start Page: 1253
• End Page: 1261
• Grant/Funding Information: National Center for Advancing Translational Sciences Clinical and Translational Science Awards at each institution (RR025008 and TR000454, Emory; RR024150 and TR000135, Mayo College of Medicine; RR033179 and TR000001, Kansas University Medical Center; RR025777, TR000165 and TR001417, University of Alabama at Birmingham; RR024153 and TR000005, University of Pittsburgh School of Medicine).; The CRISP study is supported by cooperative agreements from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (DK056943, DK056956, DK056957, DK056961), and by R01 DK113111.; This study was also supported in part by the NIDDK through P30 grants to the Kansas PKD Research and Translation Core Center (DK106912) and the Mayo Translational PKD Center (DK090728), by the National Center for Research Resources General Clinical Research Centers at each institution (RR000039, Emory University; RR00585, Mayo College of Medicine; RR23940, Kansas University Medical Center; RR000032, University of Alabama at Birmingham)
• Keywords: Life Sciences & Biomedicine; Science & Technology; Blood pressure; chronic kidney disease; Urology & Nephrology; ADPKD; Volume; Progression; MRI
• Research Categories: Health Sciences, Radiology; Health Sciences, Pathology; Health Sciences, Medicine and Surgery

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by cyst and kidney growth, which is hypothesized to cause loss of functioning renal mass and eventually end-stage kidney disease. However, the time course of decline in glomerular filtration rate (GFR) is poorly defined. The Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease study is a 14-year observational cohort study of 241 adults with ADPKD. As an estimate of the rate of kidney growth, participants were stratified into 5 subclasses based on baseline age and magnetic resonance imaging measurements of total kidney volume (TKV) according to the method of Irazabal. GFR trajectories spanning over four decades of life were reconstructed and fitted using mixed polynomial models, which were validated using data from the HALT-PKD study. GFR trajectories were nonlinear, with a period of relative stability in most participants, followed by accelerating decline. The shape and slope of these trajectories were strongly associated with baseline Irazabal class. Patients with PKD1 mutations had a steeper GFR decline than patients with PKD2 mutations or with no detected mutation, largely mediated by the effect of genotype on Irazabal class. Thus, GFR decline in ADPKD is nonlinear, and its trajectory throughout adulthood can be predicted from a single measurement of kidney volume. These models can be used for clinical prognostication, clinical trial design, and patient selection for clinical interventions. Our findings support a causal link between growth in kidney volume and GFR decline, adding support for the use of TKV as a surrogate endpoint in clinical trials.