A meta-analysis of GFR slope as a surrogate endpoint for kidney failure.

Pubmed ID: 37330614

Journal: Nature medicine

Publication Date: July 1, 2023

MeSH Terms: Humans, Bayes Theorem, Disease Progression, Kidney Failure, Chronic, Glomerular Filtration Rate, Renal Insufficiency, Chronic, Biomarkers

Grants: UL1 TR002538

Authors: Greene T, Woodward M, Neal B, Johnson D, Chalmers J, Dwyer J, Chapman A, Inker LA, Jafar TH, Remuzzi G, Ruggenenti P, Perna A, Baigent C, Perkovic V, Lewis JB, Herrington WG, Herrington WG, Landray M, Wanner C, Toto RD, Hou FF, Collier W, Miao S, Chaudhari J, Appel GB, Badve SV, Caravaca-Fontán F, Del Vecchio L, Floege J, Goicoechea M, Haaland B, Imai E, Li PKT, Maes BD, Neuen BL, Perrone RD, Schena FP, Wetzels JFM, Heerspink HJL, Estacio RO, Hanratty R, Canetta P, Barrett B, Mahaffey KW, Jardine M, von Eynatten M, Verde E, Verdalles U, Arroyo D, Torres V, Yu A, Brosnahan G, Hannedouche T, Chow KM, Szeto CC, Leung CB, Xie D, Pohl MA, Raz I, Hunsicker LG, Vanacker A, Malfait T, Maschio G, Locatelli F, Blankestijn PJ, van Zuilen A, Kobayashi F, Makino H, Chan JCN, Andrulli S, Pozzi C, Casartelli D, Praga M, Trujillo H, Cavero T, Sevillano A, Carrara F, Keane WF, Manno C, Haynes R, Rauen T, Seikrit C, Wied S, de Jong PE, Saddelli M

Cite As: Inker LA, Collier W, Greene T, Miao S, Chaudhari J, Appel GB, Badve SV, Caravaca-Fontán F, Del Vecchio L, Floege J, Goicoechea M, Haaland B, Herrington WG, Imai E, Jafar TH, Lewis JB, Li PKT, Maes BD, Neuen BL, Perrone RD, Remuzzi G, Schena FP, Wanner C, Wetzels JFM, Woodward M, Heerspink HJL, CKD-EPI Clinical Trials Consortium. A meta-analysis of GFR slope as a surrogate endpoint for kidney failure. Nat Med 2023 Jul;29(7):1867-1876. Epub 2023 Jun 17.

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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.