Where is the eye of the storm of eGFR formulas?

The estimation of glomerular filtration rate (eGFR) is central to nephrology, yet the growing number of equations often raises concern. However, only a few creatinine-based equations have gained widespread validation: Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology (CKD-EPI), and European Kidney Function Consortium (EKFC). The CG equation, introduced in 1976, was simple but imprecise. In 1999, the MDRD study equation improved GFR estimation and enabled automatic reporting by laboratories by removing weight from the formula. However, its development in patients with CKD led to GFR underestimation in healthy individuals. In 2009, the CKD-EPI equation corrected this, offering improved accuracy and less bias, except in hyperfiltration. In 2021, the CKD-EPI equation was updated to exclude race, mainly for societal reasons, though at the cost of slightly worse performance. In the same year, the EKFC equation was introduced based on European cohorts. It brought two innovations: normalization via the creatinine-to-Q ratio (Q being the median creatinine in healthy individuals), and refined age modeling. These enhancements reduced bias across both the GFR and age ranges and allowed the equation use in both adults and children. At the individual level, all equations remain estimations with similar precision, unless an additional biomarker like cystatin C is used. However, at the population level, EKFC improves bias and accuracy, especially in young adults. Switching from CKD-EPI to EKFC increases CKD prevalence moderately, as shown in European cohorts, but likely reflects better detection. Prognostic performance, particularly for cardiovascular outcomes, is maintained or improved among those reclassified to more severe CKD stages with EKFC. In summary, the EKFC equation represents a scientifically grounded progression in eGFR estimation, an evolution rather than a revolution, offering better performance and flexibility for broader clinical implementation in Europe.