Estimating glomerular filtration rate in kidney transplant recipients: considerations for selecting equations
(2024) In Kidney International 106(5). p.95-991- Abstract
- Improving the accuracy of estimated GFR (eGFR) measurement in kidney transplant recipients (KTRs) is an important goal.1 Current US and European recommendations suggest using race-free Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine-based eGFR (eGFRcr) equations (2021 age and sex [AS] or 2009 age, sex, and race–non-Black [ASR-NB]) in adults, without regard to cause or treatment of kidney disease.2,3 Participants at the Kidney Disease: Improving Global Outcomes (KDIGO) March 2022 Controversies Conference expressed concern that general population equations may perform less well in KTRs than in other adults, because KTRs were not represented adequately in the equation development populations; an additional concern was... (More)
- Improving the accuracy of estimated GFR (eGFR) measurement in kidney transplant recipients (KTRs) is an important goal.1 Current US and European recommendations suggest using race-free Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine-based eGFR (eGFRcr) equations (2021 age and sex [AS] or 2009 age, sex, and race–non-Black [ASR-NB]) in adults, without regard to cause or treatment of kidney disease.2,3 Participants at the Kidney Disease: Improving Global Outcomes (KDIGO) March 2022 Controversies Conference expressed concern that general population equations may perform less well in KTRs than in other adults, because KTRs were not represented adequately in the equation development populations; an additional concern was that a KTR-specific eGFR equation might perform better than other equations in this population.4 A recent study by Raynaud et al. suggested that a race-free creatinine-based KTR-specific (KRS 2023 AS) equation be used that was developed in a KTR population.5
We have concerns about this approach. Serum creatinine (Scr) level is affected by alterations in non-GFR determinants, including the generation, tubular secretion, and gastrointestinal elimination of creatinine, which can vary by disease, independent of measured GFR (mGFR). Although a disease-specific eGFRcr equation may be more accurate than a general population equation in patients with the disease, it may be less accurate in patients without the disease, and so the choice of equation in a patient with multiple diseases would be arbitrary and impractical. The use of different disease-specific eGFRcr equations by different specialists for a single patient could create confusion, and ultimately, it could cause harm. If alterations in non-GFR determinants of Scr level are caused by a specific disease, then including disease status as a variable in the eGFRcr equation would improve the accuracy of the equation for both those patients with versus without disease.
We previously showed that the CKD-EPI and the European Kidney Function Consortium (EKFC 2021 AS) eGFRcr equations have similar performance.6 In this study, we compared the performance of the KRS 2023 equation with the performance of these equations in an independent population, including KTRs, other solid organ–transplant recipients, and non–transplant recipients (NTRs). In a separate analysis, we evaluated whether transplant status was a significant variable in a best-fit regression model of Scr level versus mGFR. Scr assays were traceable to international standards, and mGFR was ascertained using recommended urinary or plasma clearance levels of exogenous filtration markers.
Methods
We evaluated the agreement and performance, relative to mGFR, of the KRS 2023 (AS), CKD–EPI 2021 (AS), CKD–EPI 2009 (ASR-NB), and EKFC 2021 (AS) equations, in an independent study population comprising 6580 individuals from 19 studies. We evaluated the pairwise agreement in eGFR among equations, using Deming regression (R2 on the logarithmic scale, P15, difference). We evaluated the performance of eGFR versus mGFR (R2 on the logarithmic scale, P15, P30, bias, concordance, and prediction intervals) in the overall population, as well as in subgroups (P15 and P30 were computed as the percentage of individuals with estimated eGFRs within 15% and 30% of mGFR, respectively). Confidence intervals were calculated using bootstrap methods. The complete methods are described in the Supplementary Methods in the Supplementary Material.
Results
Our study population was comprised of 6580 adults, in 19 studies, from North America and Europe, including 34.3% KTRs (n = 2258), 25.6% other solid organ–transplant recipients (n = 1685), and 40.1% NTRs (n = 2637; Table 1; Supplementary Table S1). The mean age (SD) was 51.3 (14.3) years, with 44% being women and 6.5% being Black participants. The mean (SD) mGFR was 62 (31) ml/min per 1.73 m2 in the overall population, and 51 (19), 57 (25), and 75 (38) ml/min per 1.73 m2 in KTRs, other solid organ–transplant recipients, and NTRs, respectively. (Less)
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https://lup.lub.lu.se/record/91a077f7-9e14-46a1-afc1-2e9a211d58d7
- author
- Agarwal, Krishna A
; Adingwupu, Ogechi M
; Tighiouart, Hocine
; Miao, Shiyuan
; Froissart, Marc
; Mauer, Michael
; Yang, Wei
; Torres, Vicente
; de Borst, Martin
; Klintmalm, Goran
; Poggio, Emilio D
; Rossing, Peter
; Velez, Ruben
; Grubb, Anders
LU
; Rule, Andrew D
; Shaffi, Kamran
; Chami, Ashtar
; Levey, Andrew S
and Inker, Lesley A
(Less) - organization
- publishing date
- 2024
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- cystatin C
- in
- Kidney International
- volume
- 106
- issue
- 5
- pages
- 95 - 991
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:39260523
- scopus:85206250387
- ISSN
- 1523-1755
- DOI
- 10.1016/j.kint.2024.07.035
- language
- English
- LU publication?
- yes
- id
- 91a077f7-9e14-46a1-afc1-2e9a211d58d7
- date added to LUP
- 2024-10-28 00:12:39
- date last changed
- 2025-04-04 14:50:42
@article{91a077f7-9e14-46a1-afc1-2e9a211d58d7,
abstract = {{Improving the accuracy of estimated GFR (eGFR) measurement in kidney transplant recipients (KTRs) is an important goal.1 Current US and European recommendations suggest using race-free Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine-based eGFR (eGFRcr) equations (2021 age and sex [AS] or 2009 age, sex, and race–non-Black [ASR-NB]) in adults, without regard to cause or treatment of kidney disease.2,3 Participants at the Kidney Disease: Improving Global Outcomes (KDIGO) March 2022 Controversies Conference expressed concern that general population equations may perform less well in KTRs than in other adults, because KTRs were not represented adequately in the equation development populations; an additional concern was that a KTR-specific eGFR equation might perform better than other equations in this population.4 A recent study by Raynaud et al. suggested that a race-free creatinine-based KTR-specific (KRS 2023 AS) equation be used that was developed in a KTR population.5<br/>We have concerns about this approach. Serum creatinine (Scr) level is affected by alterations in non-GFR determinants, including the generation, tubular secretion, and gastrointestinal elimination of creatinine, which can vary by disease, independent of measured GFR (mGFR). Although a disease-specific eGFRcr equation may be more accurate than a general population equation in patients with the disease, it may be less accurate in patients without the disease, and so the choice of equation in a patient with multiple diseases would be arbitrary and impractical. The use of different disease-specific eGFRcr equations by different specialists for a single patient could create confusion, and ultimately, it could cause harm. If alterations in non-GFR determinants of Scr level are caused by a specific disease, then including disease status as a variable in the eGFRcr equation would improve the accuracy of the equation for both those patients with versus without disease.<br/>We previously showed that the CKD-EPI and the European Kidney Function Consortium (EKFC 2021 AS) eGFRcr equations have similar performance.6 In this study, we compared the performance of the KRS 2023 equation with the performance of these equations in an independent population, including KTRs, other solid organ–transplant recipients, and non–transplant recipients (NTRs). In a separate analysis, we evaluated whether transplant status was a significant variable in a best-fit regression model of Scr level versus mGFR. Scr assays were traceable to international standards, and mGFR was ascertained using recommended urinary or plasma clearance levels of exogenous filtration markers.<br/>Methods<br/>We evaluated the agreement and performance, relative to mGFR, of the KRS 2023 (AS), CKD–EPI 2021 (AS), CKD–EPI 2009 (ASR-NB), and EKFC 2021 (AS) equations, in an independent study population comprising 6580 individuals from 19 studies. We evaluated the pairwise agreement in eGFR among equations, using Deming regression (R2 on the logarithmic scale, P15, difference). We evaluated the performance of eGFR versus mGFR (R2 on the logarithmic scale, P15, P30, bias, concordance, and prediction intervals) in the overall population, as well as in subgroups (P15 and P30 were computed as the percentage of individuals with estimated eGFRs within 15% and 30% of mGFR, respectively). Confidence intervals were calculated using bootstrap methods. The complete methods are described in the Supplementary Methods in the Supplementary Material.<br/>Results<br/>Our study population was comprised of 6580 adults, in 19 studies, from North America and Europe, including 34.3% KTRs (n = 2258), 25.6% other solid organ–transplant recipients (n = 1685), and 40.1% NTRs (n = 2637; Table 1; Supplementary Table S1). The mean age (SD) was 51.3 (14.3) years, with 44% being women and 6.5% being Black participants. The mean (SD) mGFR was 62 (31) ml/min per 1.73 m2 in the overall population, and 51 (19), 57 (25), and 75 (38) ml/min per 1.73 m2 in KTRs, other solid organ–transplant recipients, and NTRs, respectively.}},
author = {{Agarwal, Krishna A and Adingwupu, Ogechi M and Tighiouart, Hocine and Miao, Shiyuan and Froissart, Marc and Mauer, Michael and Yang, Wei and Torres, Vicente and de Borst, Martin and Klintmalm, Goran and Poggio, Emilio D and Rossing, Peter and Velez, Ruben and Grubb, Anders and Rule, Andrew D and Shaffi, Kamran and Chami, Ashtar and Levey, Andrew S and Inker, Lesley A}},
issn = {{1523-1755}},
keywords = {{cystatin C}},
language = {{eng}},
number = {{5}},
pages = {{95--991}},
publisher = {{Nature Publishing Group}},
series = {{Kidney International}},
title = {{Estimating glomerular filtration rate in kidney transplant recipients: considerations for selecting equations}},
url = {{http://dx.doi.org/10.1016/j.kint.2024.07.035}},
doi = {{10.1016/j.kint.2024.07.035}},
volume = {{106}},
year = {{2024}},
}