Defining a minimal clinically meaningful difference in 12-month estimated glomerular filtration rate for clinical trials in deceased donor kidney transplantation

Abstract

Background: A Minimal Clinically Meaningful Difference (MCMD) has not been defined for Estimated glomerular filtration rate (eGFR). Our goal was to define the MCMD for eGFR anchored to kidney graft failure.

Methods: A systematic review of studies with 12-month eGFR and subsequent renal graft failure was conducted. For observational studies, we calculated hazard ratio (HR) differences between adjacent eGFR intervals weighted by population distribution. Interventional trials yielded therapeutically induced changes in eGFR and failure risk. OPTN data analysis divided 12-month eGFR into bands for Cox regressions comparing adjacent eGFR bands with a death-censored graft survival outcome.

Results: Observational studies indicated that lower eGFR was associated with increased death-censored graft failure risk; each 5 ml/min/1.73 m² 12-month eGFR band associated with a weighted incremental HR = 1.12 to 1.23. Clinical trial data found a 5 ml/min/1.73 m² difference was associated with incremental HR = 1.16 to 1.35. OPTN analyses showed weighted mean HRs across 10, 7, and 5 ml/min/1.73 m² bands of 1.47, 1.30, and 1.19.

Conclusions: A 5 ml/min/1.73 m² difference in 12-month eGFR was consistently associated with ~20% increase in death-censored graft failure risk. The magnitude of effect has been interpreted as clinically meaningful in other disease states and should be considered the MCMD in renal transplantation clinical trials.

Keywords: clinical trial design; glomerular filtration rate; graft survival; kidney (allograft).