Contribution of the glomerular filtration rate slope to the kidney hierarchical composite endpoint

Abstract

Introduction: A recent chronic kidney disease (CKD) progression hierarchical composite endpoint (HCE) utilizes the glomerular filtration rate (GFR) slope for participants without a dichotomous event. Here, we evaluated clinical interpretations when HCE analyses are driven by GFR slope comparisons. Methods: Using CKD trial data, we calculated win odds using only GFR slope; dichotomous kidney events and GFR slope; all-cause mortality, dichotomous kidney events, and GFR slope; and all-cause mortality with dichotomous kidney events. Results: Win odds (95% confidence interval) calculated from pairwise GFR slope only comparisons were 1.44 (1.34–1.55), 1.60 (1.49–1.72), 1.19 (1.10–1.28), and 0.82 (0.78–0.86) in the DAPA-CKD, CREDENCE, SONAR, and ALTITUDE trials, respectively. Win odds were similar for the GFR slope only and full kidney HCE with and without mortality. Conclusions: These results support incorporation of GFR slope into the CKD progression HCE and help to interpret the magnitude of treatment effect on kidney HCE estimated with win odds.