@article{e824167b8e5e45efb01229d6235b54fd,
title = "Patterns of Kidney Function Decline in Autosomal Dominant Polycystic Kidney Disease: A Post Hoc Analysis From the HALT-PKD Trials",
abstract = "Background: Previous clinical studies of autosomal dominant polycystic kidney disease (ADPKD) reported that loss of kidney function usually follows a steep and relentless course. A detailed examination of individual patterns of decline in estimated glomerular filtration rate (eGFR) has not been performed. Study Design: Longitudinal post hoc analysis of data collected during the Halt Progression of Polycystic Kidney Disease (HALT-PKD) trials. Setting & Participants: 494 HALT-PKD Study A participants (younger; preserved eGFR) and 435 Study B participants (older; reduced eGFR) who had more than 3 years of follow-up and 7 or more eGFR assessments. Measurements: Longitudinal eGFR assessments using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine equation. Predictors: Demographic, clinical, laboratory, and imaging features of participants. Outcomes: Probability of linear and nonlinear decline patterns or of stable eGFR calculated for each participant from a Bayesian model of individual eGFR trajectories. Results: Most (62.5% in Study A and 81% in Study B) participants had a linear decline in eGFR during up to 8 years of follow-up. A proportion (22% in Study A and 13% in Study B) of progressors had a nonlinear pattern. 15.5% of participants in Study A and 6% in Study B had a prolonged (≥4.5 years) period of stable eGFRs. These individuals (Study A) had significantly smaller total kidney volumes, higher renal blood flows, lower urinary albumin excretion, and lower body mass index at baseline and study end. In Study B, participants with reduced but stable eGFRs were older than the progressors. Two-thirds of nonprogressors in both studies had PKD1 mutations, with enrichment for weak nontruncating mutations. Limitations: Relatively short follow-up of a clinical trial population. Conclusions: Although many individuals with ADPKD have a linear decline in eGFR, prolonged intervals of stable GFRs occur in a substantial fraction. Lower body mass index was associated with more stable kidney function in early ADPKD.",
keywords = "Autosomal dominant polycystic kidney disease (ADPKD), Bayesian models, eGFR slope, eGFR trajectory, end-stage renal disease (ESRD), estimated glomerular filtration rate (eGFR), kidney disease progression, mutation analysis, total kidney volume",
author = "{HALT-PKD Trial Investigators} and Brosnahan, {Godela M.} and Abebe, {Kaleab Z.} and Moore, {Charity G.} and Rahbari-Oskoui, {Frederic F.} and Bae, {Kyongtae T.} and Grantham, {Jared J.} and Schrier, {Robert W.} and Braun, {William E.} and Chapman, {Arlene B.} and Flessner, {Michael F.} and Harris, {Peter C.} and Hogan, {Marie C.} and Perrone, {Ronald D.} and Miskulin, {Dana C.} and Steinman, {Theodore I.} and Torres, {Vicente E.} and Theodore Steinman and Jesse Wei and Peter Czarnecki and Ivan Pedrosa and William Braun and Saul Nurko and Erick Remer and Arlene Chapman and Diego Martin and Frederic Rahbari-Oskoui and Pardeep Mittal and Vicente Torres and Ziad El-Zoghby and James Glockner and Bernard King and Ronald Perrone and Neil Halin and Dana Miskulin and Robert Schrier and Godela Brosnahan and Berenice Gitomer and Cass Kelleher and Amirali Masoumi and Nayana Patel and Franz Winklhofer and Jared Grantham and Alan Yu and Connie Wang and Louis Wetzel and Moore, {Charity G.} and Bost, {James E.} and Kyongtae Bae and Abebe, {Kaleab Z.} and Miller, {J. Philip}",
note = "Funding Information: Support: Supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (DK62402 to Dr Schrier, DK62411 to Dr Perrone, DK62410 to Dr Torres, DK082230 to Dr Moore, DK62408 to Dr Chapman, and DK62401 to Washington University in St. Louis) and the National Center for Research Resources General Clinical Research Centers (RR000039 to Emory University, RR000585 to the Mayo Clinic, RR000054 to Tufts Medical Center, RR000051 to the University of Colorado, RR023940 to the University of Kansas Medical Center, and RR001032 to Beth Israel Deaconess Medical Center), National Center for Advancing Translational Sciences Clinical and Translational Science Awards (RR025008 and TR000454 to Emory University, RR024150 and TR00135 to the Mayo Clinic, RR025752 and TR001064 to Tufts University, RR025780 and TR001082 to the University of Colorado, RR025758 and TR001102 to Beth Israel Deaconess Medical Center, RR033179 and TR000001 to the University of Kansas Medical Center, and RR024989 and TR000439 to Cleveland Clinic), by funding from the Zell Family Foundation (to the PKD Center at the University of Colorado for various clinical studies including HALT), and the Polycystic Kidney Disease Foundation provided financial support to the clinical centers and recruitment assistance for the enrollment phase of HALT-PKD (from 2006-2009). Mutation analysis was supported by DK62410-S1 to Dr Harris and the Mayo Translational PKD Center (DK090728). Study drugs were donated by Boehringer Ingelheim Pharmaceuticals Inc (telmisartan and matched placebo) and Merck & Co Inc (lisinopril). For the primary report of the HALT-PKD trials (published in N Engl J Med in 2014), individuals at the National Institutes of Health participated in the study design, interpretation of the data, and writing of the report. For this article, aside from Dr Flessner's authorship role, the funders had no role in the design, data collection, interpretation, and writing of the current secondary analysis or decision to submit the manuscript for publication. Publisher Copyright: {\textcopyright} 2017 National Kidney Foundation, Inc.",
year = "2018",
month = may,
doi = "10.1053/j.ajkd.2017.10.023",
language = "English (US)",
volume = "71",
pages = "666--676",
journal = "American Journal of Kidney Diseases",
issn = "0272-6386",
publisher = "W.B. Saunders Ltd",
number = "5",
}