EVALUATION OF RACE-FREE EGFR EQUATIONS IN INDIVIDUALS OF DIFFERENT ETHNICITY

Abstract

Objective: Race-free equations for estimating glomerular filtration rate (eGFR) using serum creatinine (eGFRcr), cystatin C (eGFRcys), or both (eGFRcr-cys) are digital tools used worldwide in managing CKD. However, their performance in population-based screening of low-grade CKD in Blacks and non-Blacks is unknown. Design and method: The new race-free CKD-EPI and EKFC eGFR equations were evaluated in four diverse cohorts: African-PREDICT (341/380 healthy Black and White South Africans), FLEMENGHO (709 White Flemish), NHANES (1760/7931 Black and non-Black Americans), and 401 Black African patients hospitalised in Mbuji Mayi, Democratic Republic of Congo. Results: Intraindividual discordance between eGFRs was substantial and larger in Black than non-Black NHANES and African-PREDICT participants. In NHANES, eGFRcr-cys (CDK-EPI) was greater than eGFRcr, but smaller than eGFRcys, while eGFRcr (EKFC) was smaller than eGFRcys. Replacing eGFRcr-cys by eGFRcr moved up to 25% Black and up to 15% non-Black NHANES participants to a higher (worse) eGFR KDIGO stage. In African-PREDICT and FLEMENGO, the mClcr (measured creatinine clearance) to eGFR ratios fell outside the expected 1.1–1.2 band in 50% of eGFR estimates. In NHANES, irrespective of the eGFR formulation applied, multivariable hazard ratios for total or cardiovascular mortality in relation to CKD grade and compared to the average population risk were all lower than unity for grade 1 CKD and greater than unity for grade >=3 with a trend p-value from stage 1 to >=3 of 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. Conclusions: While mortality outcomes do support use of race-free eGFR equations in population-based studies, large intraindividual variability between eGFR estimates might lead to KDIGO eGFR stage misclassification and calls for caution in opportunistic or systematic CKD screening in asymptomatic individuals with prevention as objective.