TY - JOUR
T1 - A meta-analysis of GFR slope as a surrogate endpoint for kidney failure
AU - the CKD-EPI Clinical Trials Consortium
AU - Inker, Lesley A.
AU - Collier, Willem
AU - Greene, Tom
AU - Miao, Shiyuan
AU - Chaudhari, Juhi
AU - Appel, Gerald B.
AU - Badve, Sunil V.
AU - Caravaca-Fontán, Fernando
AU - Del Vecchio, Lucia
AU - Floege, Jürgen
AU - Goicoechea, Marian
AU - Haaland, Benjamin
AU - Herrington, William G.
AU - Imai, Enyu
AU - Jafar, Tazeen H.
AU - Lewis, Julia B.
AU - Li, Philip K.T.
AU - Maes, Bart D.
AU - Neuen, Brendon L.
AU - Perrone, Ronald D.
AU - Remuzzi, Giuseppe
AU - Schena, Francesco P.
AU - Wanner, Christoph
AU - Wetzels, Jack F.M.
AU - Woodward, Mark
AU - Heerspink, Hiddo J.L.
AU - Estacio, Raymond O.
AU - Hanratty, Rebecca
AU - Chalmers, John
AU - Canetta, Pietro
AU - Barrett, Brendan
AU - Neal, Bruce
AU - Perkovic, Vlado
AU - Mahaffey, Kenneth W.
AU - Johnson, David
AU - Jardine, Meg
AU - von Eynatten, Maximilian
AU - Verde, Eduardo
AU - Verdalles, Ursula
AU - Arroyo, David
AU - Chapman, Arlene
AU - Torres, Vicente
AU - Yu, Alan
AU - Brosnahan, Godela
AU - Hannedouche, Thierry
AU - Chow, Kai Ming
AU - Szeto, Cheuk Chun
AU - Leung, Chi Bon
AU - Xie, Di
AU - Hou, Fan Fan
N1 - Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2023/7
Y1 - 2023/7
N2 - 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.
AB - 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.
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U2 - 10.1038/s41591-023-02418-0
DO - 10.1038/s41591-023-02418-0
M3 - Article
C2 - 37330614
AN - SCOPUS:85162027373
SN - 1078-8956
VL - 29
SP - 1867
EP - 1876
JO - Nature Medicine
JF - Nature Medicine
IS - 7
ER -