Race-free estimated glomerular filtration rate equation in kidney transplant recipients: development and validation study

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 P₃₀ (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/1.73m² (SD 17.23) in the development cohort and 55.90 mL/min/1.73m² (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 (P₃₀ 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 (P₃₀ 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.

Fig 1

P₃₀ (proportion of eGFR within 30% of mGFR) and correct classification (agreement between eGFR and mGFR according to GFR stages) metrics for four GFR equations in development cohort and external validation cohorts. eGFR was calculated on the basis of recipient creatinine level, age, sex, and race (if required by the equation). ABCAN=Angiotensin II Blockade for Chronic Allograft Nephropathy; BENEFIT=Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial; BENEFIT-EXT=Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial-EXTended criteria donors; CKD-EPI=Chronic Kidney Disease Epidemiology Collaboration; GFR=glomerular filtration rate; eGFR=estimated glomerular filtration rate; KRS=kidney recipient specific; mGFR=measured glomerular filtration rate; MDRD=Modification of Diet in Renal Disease

Fig 2

Distribution of eGFR according to mGFR in development cohort and external validation cohorts. eGFR was calculated with the kidney recipient specific GFR equation on the basis of recipient creatinine level, age, and sex. P₃₀ is the proportion of eGFR within 30% of mGFR. Correct classification is the agreement between eGFR and mGFR according to GFR stages. ABCAN=Angiotensin II Blockade for Chronic Allograft Nephropathy; BENEFIT=Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial; BENEFIT-EXT=Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial-EXTended criteria donors; CKD-EPI=Chronic Kidney Disease Epidemiology Collaboration; GFR=glomerular filtration rate; eGFR=estimated glomerular filtration rate; KRS=kidney recipient specific; mGFR=measured glomerular filtration rate

Fig 3

P₃₀ (proportion of eGFR within 30% of mGFR) and correct classification (agreement between eGFR and mGFR according to GFR stages) metrics for four GFR equations in external validation cohorts when stratified by race, sex, age (threshold set at median), and donor type. eGFR was calculated with race-free kidney recipient specific GFR equation on basis of recipient creatinine level, age, and sex. Supplementary figures 5-35 show comparisons with Modification of Diet in Renal Disease, CKD-EPI 2009, and race-free CKD-EPI 2021 equations. eGFR=estimated glomerular filtration rate; KRS=kidney recipient specific; mGFR=measured glomerular filtration rate