# Evaluation of race-free eGFR equations in individuals of different ethnicity

## TL;DR

This study evaluates race-free equations for estimating kidney function and finds they work well overall but may misclassify some individuals, especially Black patients.

## Contribution

The study provides new evidence on the performance of race-free eGFR equations in multi-ethnic populations and their association with mortality.

## Key findings

- Race-free eGFR equations showed good reproducibility but large intraindividual variability in estimates.
- eGFRcr-cys and eGFRcys were better predictors of mortality than eGFRcr.
- Misclassification of CKD stages was observed in Black individuals when using eGFRcr.

## Abstract

Glomerular filtration rate (eGFR) derived from serum creatinine (eGFRcr), cystatin C (eGFRcys), or both (eGFRcr-cys) by race-free equations are recommended staging chronic kidney disease (CKD). The current study aimed to compare these race-free eGFR equations for screening for low-grade CKD in Blacks and non-Blacks and to evaluate their association with mortality.

Race-free eGFR equations were evaluated in four studies with specific inclusion criteria based on the original research goals: African-PREDICT (341/380 healthy Black/White South Africans), FLEMENGHO (709 White community-dwelling Flemish), NHANES (1760/7931 Black and non-Black adult Americans), and 401 Black African patients hospitalised in Mbuji Mayi, Democratic Republic of Congo. The intraclass correlation coefficient and Bland and Altman statistics were used to assess consistency between eGFR equations and multivariable logistic or Cox regression to evaluate their association with mortality.

Intraindividual discordance between eGFRs was larger in Black than non-Black NHANES and African-PREDICT participants. In NHANES, eGFRcr-cys was greater than eGFRcr, but smaller than eGFRcys, and replacing eGFRcr-cys by eGFRcr moved 25% Blacks and 15% non-Blacks to a higher (worse) eGFR KDIGO stage. In African-PREDICT and FLEMENGO, half of the measured creatinine clearance to eGFR ratios fell outside the expected 1.1–1.2 band. In NHANES, multivariable hazard ratios for total and cardiovascular mortality in relation to CKD grade were all lower than unity for grade-1 CKD and greater than unity for grade ≥3 (p < 0.0001) without any racial difference (0.11≤p ≤ 0.98). These NHANES findings were consistent, if CKD stage was replaced by eGFR and in subgroup analyses. Whereas eGFRcys and eGFRcr-cys refined models, eGFRcr did not.

The NHANES mortality outcomes support the use of eGFRcys and eGFRcr-cys. However, large intraindividual variability between eGFR estimates may lead to KDIGO eGFR stage misclassification and calls for caution in the opportunistic or systematic screening for CKD in asymptomatic individuals with prevention as objective.

Glomerular filtration rate reflects the ability to remove excess water and waste by the kidney and can be estimated from serum creatinine (eGFR). However, serum creatinine is affected by muscle mass, dietary habits and other factors that cluster by race and lead to overestimation of eGFR and underestimation of the risk of kidney disease in Black individuals. Serum cystatin C is less affected by these confounders. Equations to compute eGFR from serum cystatin C or both serum creatinine and cystatin C without considering race are currently recommended. This study evaluated these race-free equations to compute eGFR in multi-ethnic study populations recruited in South Africa, Belgium, the Democratic Republic of the Congo and the United States. The new methods produce eGFR estimates, which predict mortality and have near perfect reproducibility in the population as a whole. However, this study also identified large intraindividual differences between eGFR estimates that may lead to misclassification of patients with regard to their renal function. These observations call for caution in the clinical application of equations to derive eGFR from serum markers and highlight the need for further research to optimise the prevention and management of chronic kidney disease.