Estimated glomerular filtration rate (eGFR) is one of the most crucial factors to assess kidney functions, and it is based on endogenous filtration markers like creatinine. Many factors independent of glomerular filtration can influence the serum level of creatinine and compromise the eGFR accuracy. One of such factors is the production rate of creatinine, which was found to be associated with race because of the difference in body muscle mass. Since the development of the MDRD equation, a binary race factor (black vs non-black) has been adopted and also retained in the CKD-EPI 2009 equation. However, this approach has been challenged by the ambiguity in race assignment, lack of evidence for clinical benefits, and inequity in healthcare system. Also, race is a social and not a biologic construct. Prior to the CKD-EPI 2021 equation, one option for race-independent eGFR calculation is to omit the race factor and use the non-black (NB) version of equations for all patients regardless of race, and this has been done for both MDRD (MDRD_NB) and CKD-EPI 2009 (CKD-EPI 2009_NB) equations in the US. In Europe, the European Kidney Function Consortium (EKFC) equation provides an alternative solution.

The CKD-EPI 2021 equation is obtained by refitting the data used to develop the CKD-EPI 2009 equation without the race factor, so it is more statistically accurate than the race factor-omitted equations (MDRD_NB and CKD-EPI 2009_NB). Numerically, eGFR calculated by CKD-EPI 2021 lies between the results of CKD-EPI 2009 and CKD-EPI 2009_NB given identical serum creatinine and age (1). The MDRD equation is derived from a population with low GFR, so it tends to underestimate GFR especially when eGFR > 60 mL/min/1.73m2. The EKFC equation aims at a universal eGFR formula for all age groups by combining characteristics of the full age spectrum (FAS) equation and CKD-EPI 2009 (2). The algorithm is different from the CKD-EPI and MDRD equations because EKFC places more weight to age correction.

We have conducted a study to compare these race-independent eGFR equations in a local patient population dominated by white people (3). Both race factor-omitted equations (CKD-EPI 2009_NB and MDRD_NB) and EKFC generate a lower eGFR compared to the CKD-EPI 2021 equation when eGFR < 90 mL/min/1.73m2. At the medical decision level for CKD (60 mL/min/1.73m2), CKD-EPI 2009_NB is consistent with the CKD-EPI 2021 equation in classification (kappa = 0.79), whereas the other two equations classify more patients as CKD (kappa = 0.61 and 0.59). In CKD staging, both CKD-EPI 2009_NB and MDRD_NB show an overall agreement with the new equation (kappa = 0.85, 0.90) although they tend to classify more patients from G3a to G3b stage, but such discordance becomes significant for EKFC equation (kappa = 0.79). Nevertheless, all equations result in a similar classification for the terminal G5 stage.

Therefore, CKD-EPI 2021 equation implementation is not expected to cause a significant reclassification for institutions using the CKD-EPI 2009_NB equation, but a decrease in early stage CKD patients may be seen if the MDRD_NB equation is used. Transition from EKFC to CKD-EPI 2021 may result in a decrease of total CKD patients and reclassification to a less advanced CKD stage.

References

  1. Inker LA, Eneanya ND, Coresh J, Tighiouart H, Wang D, Sang Y, et al. New Creatinine- and Cystatin C-Based Equations to Estimate GFR without Race. N Engl J Med 2021;385:1737-49.
  2. Pottel H, Bjork J, Courbebaisse M, Couzi L, Ebert N, Eriksen BO, et al. Development and Validation of a Modified Full Age Spectrum Creatinine-Based Equation to Estimate Glomerular Filtration Rate: A Cross-sectional Analysis of Pooled Data. Ann Intern Med 2021;174:183-91.
  3. Lu S, Robyak K, Zhu Y. The CKD-EPI 2021 Equation and Other Creatinine-Based Race-Independent eGFR Equations in Chronic Kidney Disease Diagnosis and Staging. J Appl Lab Med. 2023 Aug 3:jfad047. doi: 10.1093/jalm/jfad047. Epub ahead of print. PMID: 37534520.