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

Abstract

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. 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. 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. 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.