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

Abstract

Background Glomerular filtration rate (eGFR) derived from serum creatinine (eGFR(cr)), cystatin C (eGFR(cys)), or both (eGFR(cr-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. Methods 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. Results Intraindividual discordance between eGFRs was larger in Black than non-Black NHANES and African-PREDICT participants. In NHANES, eGFR(cr-cys) was greater than eGFR(cr), but smaller than eGFR(cys), and replacing eGFR(cr-cys) by eGFR(cr) 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 eGFR(cys) and eGFR(cr-cys) refined models, eGFR(cr) did not. Conclusions The NHANES mortality outcomes support the use of eGFR(cys) and eGFR(cr-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.