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Publication Information

PubMed ID
Public Release Type
Journal
Publication Year
2022
Affiliation
The George Institute for Global Health, University of New South Wales, Sydney, Australia Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, MA, USA Tufts Clinical and Translational Science Institute, Tufts University, Boston, MA, USA Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands Department of Preventive Medicine, Division of Biostatistics, Northwestern University, Chicago, IL, USA Division of Nephrology, Tufts Medical Center, Boston, MA, USA Department of Medicine, University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong Division of Nephrology and Hypertension and Department of Medicine, Mayo Clinic Rochester, MN, USA 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,, 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 Duke Global Health Institute, Duke University, Durham, North Carolina 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 Nephrology Department, Hospital Universitario 12 de Octubre, Madrid, Spain 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 Division of Nephrology, University Hospital of Würzburg, Würzburg, Germany Department of Nephrology, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands The George Institute for Global Health, School of Public Health, Imperial College London, UK Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China Division of Epidemiology, Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA
Authors
Chan TM, Chaudhari J, Fervenza FC, Floege J, Goicoechea M, Greene T, Heerspink HJL, Herrington WG, Imai E, Inker LA, Jafar TH, Kam-Tao Li P, Lewis JB, Locatelli F, Maes BD, Miao S, Neuen BL, Perna A, Perrone RD, Praga M, Schena FP, Tighiouart H, Vonesh EF, Wanner C, Wetzels JFM, Woodward M, Xie D
Studies

Abstract

Background Acute changes in glomerular filtration rate (GFR) can occur following initiation of interventions for chronic kidney disease (CKD) progression. These complicate the interpretation of treatment effects on long term progression of (CKD). We sought to assess the magnitude and consistency of acute effects in randomized clinical trials (RCT) and explore factors that might impact them. Methods We performed a meta-analysis of 53 RCTs for CKD progression enrolling 56,413 participants that had at least one estimated GFR measurement by six months following randomization. We defined acute treatment effects as the mean difference in GFR slope from baseline to 3 months between randomized groups. We performed univariable and multivariable meta-regression to assess the impact of intervention type, disease state, baseline GFR and albuminuria on the magnitude of acute effects. Results The mean acute effect across all studies was -0.21 mL/min/1.73m2 (95% CI -0.63 to 0.22) over three months, with substantial heterogeneity across interventions (95% coverage interval across studies, -2.50 to +2.08 mL/min/1.73m2). Negative average acute effects were observed in renin angiotensin system blockade, blood pressure lowering and sodium-glucose cotransporter 2 inhibitor trials while positive acute effects were observed in trials of immunosuppressive agents. Larger negative acute effects were observed in trials with higher mean baseline GFR. Conclusion The magnitude and consistency of acute GFR effects varies across different interventions, and is larger at higher baseline GFR. Understanding the nature and magnitude of the acute effects can help inform the optimal design of RCTs in CKD evaluating kidney disease progression.