New and old GFR equations: a European perspective

Glomerular filtration rate (GFR) is estimated in clinical practice from equations based on the serum concentration of endogenous biomarkers and demographic data. The 2009 creatinine-based Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI₂₀₀₉) was recommended worldwide until 2021, when it was recalibrated to remove the African-American race factor. The CKD-EPI₂₀₀₉ and CKD-EPI_cr2021 equations overestimate GFR of adults aged 18-30 years, with a strong overestimation in estimated GFR (eGFR) at age 18 years. CKD-EPI_Cr2021 does not perform better than CKD-EPI₂₀₀₉ in US population, overestimating GFR in non-Black subjects, and underestimating it in Black subjects with the same magnitude. CKD-EPI_Cr2021 performed worse than the CKD-EPI₂₀₀₉ in White Europeans, and provides no or limited performance gains in Black European and Black African populations. The European Kidney Function Consortium (EKFC) equation, which incorporates median normal value of serum creatinine in healthy population, overcomes the limitations of the CKD-EPI equations: it provides a continuity of eGFR at the transition between pediatric and adult care, and performs reasonably well in diverse populations, assuming dedicated scaling of serum creatinine (Q) values is used. The new EKFC equation based on cystatin C (EKFC_CC) shares the same mathematical construction, namely, it incorporates the median cystatin C value in the general population, which is independent of sex and ethnicity. EKFC_CC is therefore a sex-free and race-free equation, which performs better than the CKD-EPI equation based on cystatin C. Despite advances in the field of GFR estimation, no equation is perfectly accurate, and GFR measurement by exogenous tracer clearance is still required in specific populations and/or specific clinical situations.