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

Marc Raynaud; Solaf Al-Awadhi; Ivana Juric; Gillian Divard; Yannis Lombardi; Nikolina Basic-Jukic; Olivier Aubert; Laurence Dubourg; Ingrid Masson; Christophe Mariat; Dominique Prié; Vincent Pernin; Moglie Le Quintrec; Timothy S Larson; Mark D Stegall; Boris Bikbov; Piero Ruggenenti; Laurent Mesnard; Hassan N Ibrahim; Marie Bodilsen Nielsen; Arthur J Matas; Brian J Nankivell; Stan Benjamens; Robert A Pol; Stephan J L Bakker; Xavier Jouven; Christophe Legendre; Nassim Kamar; Byron H Smith; Hani M Wadei; Antoine Durrbach; Flavio Vincenti; Giuseppe Remuzzi; Carmen Lefaucheur; Andrew J Bentall; Alexandre Loupy

doi:10.1136/bmj-2022-073654

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

Marc Raynaud, Solaf Al-Awadhi, Ivana Juric, Gillian Divard, Yannis Lombardi, Nikolina Basic-Jukic, Olivier Aubert, Laurence Dubourg, Ingrid Masson, Christophe Mariat, Dominique Prié, Vincent Pernin, Moglie Le Quintrec, Timothy S Larson, Mark D Stegall, Boris Bikbov, Piero Ruggenenti, Laurent Mesnard, Hassan N Ibrahim, Marie Bodilsen NielsenArthur J Matas, Brian J Nankivell, Stan Benjamens, Robert A Pol, Stephan J L Bakker, Xavier Jouven, Christophe Legendre, Nassim Kamar, Byron H Smith, Hani M Wadei, Antoine Durrbach, Flavio Vincenti, Giuseppe Remuzzi, Carmen Lefaucheur, Andrew J Bentall, Alexandre Loupy^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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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.

Original language	English
Article number	e073654
Number of pages	12
Journal	BMJ (Clinical research ed.)
Volume	381
DOIs	https://doi.org/10.1136/bmj-2022-073654
Publication status	Published - 31-May-2023

Keywords

Adult
Humans
Glomerular Filtration Rate
Kidney Transplantation
Creatinine
Kidney
Renal Insufficiency, Chronic/diagnosis

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Raynaud, M., Al-Awadhi, S., Juric, I., Divard, G., Lombardi, Y., Basic-Jukic, N., Aubert, O., Dubourg, L., Masson, I., Mariat, C., Prié, D., Pernin, V., Le Quintrec, M., Larson, T. S., Stegall, M. D., Bikbov, B., Ruggenenti, P., Mesnard, L., Ibrahim, H. N., ... Loupy, A. (2023). Race-free estimated glomerular filtration rate equation in kidney transplant recipients: development and validation study. BMJ (Clinical research ed.), 381, Article e073654. https://doi.org/10.1136/bmj-2022-073654

@article{dab62753b4cc4272bf3d3f8a5f4a06d1,

title = "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 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.",

keywords = "Adult, Humans, Glomerular Filtration Rate, Kidney Transplantation, Creatinine, Kidney, Renal Insufficiency, Chronic/diagnosis",

author = "Marc Raynaud and Solaf Al-Awadhi and Ivana Juric and Gillian Divard and Yannis Lombardi and Nikolina Basic-Jukic and Olivier Aubert and Laurence Dubourg and Ingrid Masson and Christophe Mariat and Dominique Pri{\'e} and Vincent Pernin and {Le Quintrec}, Moglie and Larson, {Timothy S} and Stegall, {Mark D} and Boris Bikbov and Piero Ruggenenti and Laurent Mesnard and Ibrahim, {Hassan N} and Nielsen, {Marie Bodilsen} and Matas, {Arthur J} and Nankivell, {Brian J} and Stan Benjamens and Pol, {Robert A} and Bakker, {Stephan J L} and Xavier Jouven and Christophe Legendre and Nassim Kamar and Smith, {Byron H} and Wadei, {Hani M} and Antoine Durrbach and Flavio Vincenti and Giuseppe Remuzzi and Carmen Lefaucheur and Bentall, {Andrew J} and Alexandre Loupy",

note = "{\textcopyright} Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.",

year = "2023",

month = may,

day = "31",

doi = "10.1136/bmj-2022-073654",

language = "English",

volume = "381",

journal = "BMJ (Clinical research ed.)",

issn = "0959-8138",

publisher = "BMJ Publishing Group",

}

Raynaud, M, Al-Awadhi, S, Juric, I, Divard, G, Lombardi, Y, Basic-Jukic, N, Aubert, O, Dubourg, L, Masson, I, Mariat, C, Prié, D, Pernin, V, Le Quintrec, M, Larson, TS, Stegall, MD, Bikbov, B, Ruggenenti, P, Mesnard, L, Ibrahim, HN, Nielsen, MB, Matas, AJ, Nankivell, BJ, Benjamens, S, Pol, RA , Bakker, SJL, Jouven, X, Legendre, C, Kamar, N, Smith, BH, Wadei, HM, Durrbach, A, Vincenti, F, Remuzzi, G, Lefaucheur, C, Bentall, AJ & Loupy, A 2023, 'Race-free estimated glomerular filtration rate equation in kidney transplant recipients: development and validation study', BMJ (Clinical research ed.), vol. 381, e073654. https://doi.org/10.1136/bmj-2022-073654

TY - JOUR

T1 - Race-free estimated glomerular filtration rate equation in kidney transplant recipients

T2 - development and validation study

AU - Raynaud, Marc

AU - Al-Awadhi, Solaf

AU - Juric, Ivana

AU - Divard, Gillian

AU - Lombardi, Yannis

AU - Basic-Jukic, Nikolina

AU - Aubert, Olivier

AU - Dubourg, Laurence

AU - Masson, Ingrid

AU - Mariat, Christophe

AU - Prié, Dominique

AU - Pernin, Vincent

AU - Le Quintrec, Moglie

AU - Larson, Timothy S

AU - Stegall, Mark D

AU - Bikbov, Boris

AU - Ruggenenti, Piero

AU - Mesnard, Laurent

AU - Ibrahim, Hassan N

AU - Nielsen, Marie Bodilsen

AU - Matas, Arthur J

AU - Nankivell, Brian J

AU - Benjamens, Stan

AU - Pol, Robert A

AU - Bakker, Stephan J L

AU - Jouven, Xavier

AU - Legendre, Christophe

AU - Kamar, Nassim

AU - Smith, Byron H

AU - Wadei, Hani M

AU - Durrbach, Antoine

AU - Vincenti, Flavio

AU - Remuzzi, Giuseppe

AU - Lefaucheur, Carmen

AU - Bentall, Andrew J

AU - Loupy, Alexandre

PY - 2023/5/31

Y1 - 2023/5/31

N2 - 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.

AB - 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.

KW - Adult

KW - Humans

KW - Glomerular Filtration Rate

KW - Kidney Transplantation

KW - Creatinine

KW - Kidney

KW - Renal Insufficiency, Chronic/diagnosis

U2 - 10.1136/bmj-2022-073654

DO - 10.1136/bmj-2022-073654

M3 - Article

C2 - 37257905

SN - 0959-8138

VL - 381

JO - BMJ (Clinical research ed.)

JF - BMJ (Clinical research ed.)

M1 - e073654

ER -

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

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