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Publication Information

PubMed ID
Public Release Type
Journal
Publication Year
2023
Affiliation
Population Health Sciences, University of Utah School of Medicine, UT, USA Division of Nephrology, Tufts Medical Center, Boston, MA USA Division of Nephrology, Columbia University Medical Center and the New York Presbyterian Hospital, New York, NY, USA Renal and Metabolic Division, the George Institute for Global Health, NSW, Australia Instituto de Investigación Hospital 12 de octubre (i+12), Madrid, Spain The George Institute for Global Health, University of New South Wales, Sydney, Australia Division of Nephrology, RWTH Aachen University, Aachen, Germany Department of Nephrology, Hospital General Universitario Gregorio Marañón, Madrid, Spain Medical Research Council Population Health Research Unit at the University of Oxford, Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, 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, Alessandro Manzoni Hospital ( past Director), ASST Lecco, Italy 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 Division of Nephrology, University Hospital of Würzburg, Würzburg, Germany Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China
Authors
Appel GB, Badve S, Caravaca-Fontán F, Chalmers J, Collier W, Floege J, Goicoechea M, Greene T, Haaland B, Haynes R, Imai E, Inker LA, Jafar TH, Lewis JB, Li PKT, Locatelli F, Maes B, Neuen BL, Perrone RD, Remuzzi G, Schena FP, Toto RD, Wanner C, Xie D

Abstract

Backround and objectives: The GFR slope has been evaluated as a surrogate end point for kidney failure in meta-analyses on a broad collection of randomized controlled trials (RCTs) in CKD. These analyses evaluate how accurately a treatment effect on GFR slope predicts a treatment effect on kidney failure. We sought to determine whether severity of CKD in the patient population modifies the performance of GFR slope. Design, setting, participants, and measurements: We performed Bayesian meta-regression analyses on 66 CKD RCTs to evaluate associations between effects on GFR slope (the chronic slope and the total slope over 3 years, expressed as mean differences in ml/min per 1.73 m2/yr) and those of the clinical end point (doubling of serum creatinine, GFR <15 ml/min per 1.73 m2, or kidney failure, expressed as a log-hazard ratio), where models allow interaction with variables defining disease severity. We evaluated three measures (baseline GFR in 10 ml/min per 1.73 m2, baseline urine albumin-to-creatinine ratio [UACR] per doubling in mg/g, and CKD progression rate defined as the control arm chronic slope, in ml/min per 1.73 m2/yr) and defined strong evidence for modification when 95% posterior credible intervals for interaction terms excluded zero. Results There was no evidence for modification by disease severity when evaluating 3-year total slope (95% credible intervals for the interaction slope: baseline GFR [-0.05 to 0.03]; baseline UACR [-0.02 to 0.04]; CKD progression rate [-0.07 to 0.02]). There was strong evidence for modification in evaluations of chronic slope (95% credible intervals: baseline GFR [0.02 to 0.11]; baseline UACR [-0.11 to -0.02]; CKD progression rate [0.01 to 0.15]). Conclusions: These analyses indicate consistency of the performance of total slope over 3 years, which provides further evidence for its validity as a surrogate end point in RCTs representing varied CKD populations.