Race-free estimated glomerular filtration rate equation in kidney transplant recipients: development and validation study
Authors: Raynaud Marc , Al-Awadhi Solaf , Juric Ivana , Divard Gillian , Lombardi Yannis , Basic-Jukic Nikolina , Aubert Olivier , Dubourg Laurence , Masson Ingrid , Mariat Christophe , Prié Dominique , Pernin Vincent , Le Quintrec Moglie , Larson Timothy S , Stegall Mark D , Bikbov Boris , Ruggenenti Piero , Mesnard Laurent , Ibrahim Hassan N , Nielsen Marie Bodilsen , Matas Arthur J , Nankivell Brian J , Benjamens Stan , Pol Robert A , Bakker Stephan J L , Jouven Xavier , Legendre Christophe , Kamar Nassim , Smith Byron H , Wadei Hani M , Durrbach Antoine , Vincenti Flavio , Remuzzi Giuseppe , Lefaucheur Carmen , Bentall Andrew J , Loupy Alexandre 
Published: May 2023

Abstract

Objective
To compare the performance of a newly developed race-free kidney recipient specific glomerular filtration rate (GFR) equation with the three current main equations for measuring GFR in kidney transplant recipients.

Design
Development and validation study

Setting
17 cohorts in Europe, the United States, and Australia (14 transplant centres, three clinical trials).

Participants
15 489 adults (3622 in development cohort (Necker, Saint Louis, and Toulouse hospitals, France), 11 867 in multiple external validation cohorts) who received kidney transplants between 1 January 2000 and 1 January 2021.

Main outcome measure

The main outcome measure was GFR, measured according to local practice. Performance of the GFR equations was assessed using P
30
(proportion of estimated GFR (eGFR) within 30% of measured GFR (mGFR)) and correct classification (agreement between eGFR and mGFR according to GFR stages). The race-free equation, based on creatinine level, age, and sex, was developed using additive and multiplicative linear regressions, and its performance was compared with the three current main GFR equations: Modification of Diet in Renal Disease (MDRD) equation, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2009 equation, and race-free CKD-EPI 2021 equation.

Results

The study included 15 489 participants, with 50 464 mGFR and eGFR values. The mean GFR was 53.18 mL/min/1.73m
2
(SD 17.23) in the development cohort and 55.90 mL/min/1.73m
2
(19.69) in the external validation cohorts. Among the current GFR equations, the race-free CKD-EPI 2021 equation showed the lowest performance compared with the MDRD and CKD-EPI 2009 equations. When race was included in the kidney recipient specific GFR equation, performance did not increase. The race-free kidney recipient specific GFR equation showed significantly improved performance compared with the race-free CKD-EPI 2021 equation and performed well in the external validation cohorts (P
30
ranging from 73.0% to 91.3%). The race-free kidney recipient specific GFR equation performed well in several subpopulations of kidney transplant recipients stratified by race (P
30
73.0-91.3%), sex (72.7-91.4%), age (70.3-92.0%), body mass index (64.5-100%), donor type (58.5-92.9%), donor age (68.3-94.3%), treatment (78.5-85.2%), creatinine level (72.8-91.3%), GFR measurement method (73.0-91.3%), and timing of GFR measurement post-transplant (72.9-95.5%). An online application was developed that estimates GFR based on recipient’s creatinine level, age, and sex (
https://transplant-prediction-system.shinyapps.io/eGFR_equation_KTX/
).

Conclusion
A new race-free kidney recipient specific GFR equation was developed and validated using multiple, large, international cohorts of kidney transplant recipients. The equation showed high accuracy and outperformed the race-free CKD-EPI 2021 equation that was developed in individuals with native kidneys.

Trial registration

ClinicalTrials.gov
NCT05229939
.