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. 2021 Jul;35(7):e14326.
doi: 10.1111/ctr.14326. Epub 2021 May 5.

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

Tracy J Mayne  1 , Robert J Nordyke  1 , Jesse D Schold  2 , Matthew R Weir  3 , Sumit Mohan  4
Affiliations

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

Tracy J Mayne et al. Clin Transplant. 2021 Jul.

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).

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Conflict of interest statement

Sumit Mohan, Jesse Schold, and Matthew Weir have received research funding and/or consultancy fees unrelated to this study from Angion Biomedica. Tracy Mayne was an employee of Angion Biomedica at the time of this study. Robert Nordyke is an employee of Angion Biomedica and owns stock/stock options.

Figures

FIGURE 1
FIGURE 1
Combined figures from observational studies: relationship between 12‐month eGFR and all‐cause graft failure
FIGURE 2
FIGURE 2
Change in all‐cause graft failure hazard ratio by eGFR
FIGURE 3
FIGURE 3
12‐month eGFR plotted against graft failure in 3 randomized controlled trials
FIGURE 4
FIGURE 4
Hazard ratio for death‐censored graft failure by eGFR band by percent of population within each eGFR band
See this image and copyright information in PMC

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