A proposal to analyze the progression of non-dialytic chronic kidney disease by surrogate endpoints: introducing parametric survival models

Abstract

IntroductionChronic kidney disease (CDK) progression studies increasingly use surrogate endpoints based on the estimated glomerular filtration rate. The clinical characteristics of these endpoints bring new challenges in comparing groups of patients, as traditional Cox models may lead to biased estimates mainly because they do not assume a hazard function.ObjectiveThis study proposes the use of parametric survival analysis models with the three most commonly used endpoints in nephrology based on a case study. Estimated glomerular filtration rate (eGFR) decay > 5 mL/year, eGFR decline > 30%, and change in CKD stage were evaluated.MethodThe case study is a 5-year retrospective cohort study that enrolled 778 patients in the predialysis stage. Exponential, Weibull, Gompertz, lognormal, and logistic models were compared, and proportional hazard and accelerated failure time (AFT) models were evaluated.ResultsThe endpoints had quite different hazard functions, demonstrating the importance of choosing appropriate models for each. AFT models were more suitable for the clinical interpretation of the effects of covariates on these endpoints.ConclusionSurrogate endpoints have different hazard distributions over time, which is already recognized by nephrologists. More flexible analysis techniques that capture these relevant clinical characteristics in decision-making should be encouraged and disseminated in nephrology research.