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Publication Information
Affiliation
Division of Nephrology, Tufts Medical Center, Boston, MA USA
Population Health Sciences, University of Utah School of Medicine, UT, USA
Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
Renal and Metabolic Division, the George Institute for Global Health, NSW, Australia
Instituto de Investigación Hospital 12 de octubre (i+12), Madrid, Spain
Division of Nephrology, RWTH Aachen University, Aachen, Germany
Department of Nephrology, Hospital General Universitario Gregorio Marañón, Madrid, Spain
Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
Nakayamadera Imai Clinic, Takarazuka, Japan
Program in Health Services and Systems Research, Duke-NUS Medical School, Singapore
Division of Nephrology, Vanderbilt University, Nashville, TN, USA
Division of Nephrology, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, Hong Kong
Department of Nephrology, AZ Delta, Roeselare, Belgium
Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy
Renal, Dialysis and Transplant Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA
Department of Nephrology and Dialysis, Sant’Anna Hospital, ASST Lariana, 22042 Como, Italy
Division of Nephrology, University Hospital of Würzburg, Würzburg, Germany
The George Institute for Global Health, University of New South Wales, Sydney, Australia
Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China
Authors
Appel GB, Badve SV, Caravaca-Fontán F, Chaudhari J, Collier W, del Vecchio L, Floege J, Goicoechea M, Greene T, Haaland B, Heerspink HJL, Herrington WG, Imai E, Inker LA, Jafar TH, Lewis JB, Li PKT, Maes BD, Miao S, Neuen BL, Perrone RD, Remuzzi G, Schena FP, Wanner C, Wetzels JFM, Woodward M
Abstract
Glomerular filtration rate (GFR) decline is causally associated with kidney failure and is a candidate surrogate endpoint for clinical trials of chronic kidney disease (CKD) progression. Analyses across a diverse spectrum of interventions and populations is required for acceptance of GFR decline as an endpoint. In an analysis of individual participant data, for each of 66 studies (total of 186,312 participants), we estimated treatment effects on the total GFR slope, computed from baseline to 3 years, and chronic slope, starting at 3 months after randomization, and on the clinical endpoint (doubling of serum creatinine, GFR < 15 ml min−1 per 1.73 m2 or kidney failure with replacement therapy). We used a Bayesian mixed-effects meta-regression model to relate treatment effects on GFR slope with those on the clinical endpoint across all studies and by disease groups (diabetes, glomerular diseases, CKD or cardiovascular diseases). Treatment effects on the clinical endpoint were strongly associated with treatment effects on total slope (median coefficient of determination (R2) = 0.97 (95% Bayesian credible interval (BCI) 0.82–1.00)) and moderately associated with those on chronic slope (R2 = 0.55 (95% BCI 0.25–0.77)). There was no evidence of heterogeneity across disease. Our results support the use of total slope as a primary endpoint for clinical trials of CKD progression.