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Improving Glomerular Filtration Rate Estimation—Across the Age and Diversity Spectrum

and Diversity Spectrum A of glomerular filtration rate (GFR) is central to medical practice, research, and public health. In an update to its chronic kidney disease guideline, KDIGO (Kidney Disease: Improving Global Outcomes) recommends estimating GFR by measuring serum creatinine (SCr) levels as an initial test but acknowledges that estimated GFR (eGFR) is less accurate than measured GFR (mGFR); therefore, KDIGO recommends subsequent confirmatory testing (estimating GFR by using serum cystatin C, measured creatinine clearance, or mGFR) if greater accuracy is needed for clinical decision making. The guideline recommends using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for adults (with variables including SCr level, age, sex, and Black vs. non-Black race) and the Chronic Kidney Disease in Children Study (CKiD) equation for children (with variables including SCr level, age, sex, and height) unless other equations are more accurate. The rationale for recommending single equations for adults and children whenever possible was to facilitate uniformity of best practices and ease of communication. Since the updated guideline was published, new equations have been developed for adults in White populations in Europe and North America, but they have not substantially improved performance compared with the CKD-EPI equation (1). This may reflect the limited accuracy in estimating GFR from SCr levels because of variation in non-GFR determinants of SCr and errors in mGFR (2). However, discontinuity exists during the transition from adolescence to young adulthood with use of the CKiD and CKD-EPI equations, which may be mitigated by averaging the results (3). A single equation that is useful for the full age spectrum (FAS) that eliminates this discontinuity and is at least as accurate as the CKD-EPI and CKiD equations in diverse populations would be desirable. In their current Annals report, Pottel and colleagues from the European Kidney Function Consortium (EKFC) describe a new estimating equation and conclude that it satisfies these expectations (4). Previously, Pottel and colleagues developed a FAS equation that uses assumed ageand sex-stratified normal values for SCr (Q) and age-stratified normal values for mGFR to eliminate the discontinuity in eGFR during the transition from adolescence to young adulthood (5). In their current work, the authors developed the EKFC equation (with variables including SCr level, age, sex, and Q) by combining design features of the FAS and CKD-EPI equations (a 2-slope spline for the regression of mGFR on SCr values on the logarithmic scale, with a less steep slope at low SCr levels). The equation was developed in a study population of 11 251 participants in 7 studies and was validated in a separate study population of 8378 participants in 6 studies. All studies had been performed in Europe and North America and included only White participants. The EKFC equation was unbiased across all age groups (median bias near zero), and P30 accuracy (percentage of eGFR within 30% of mGFR) was approximately 80% in children (aged 2 to 18 years) and ranged from 85% to 90% in adults (>18 years). Performance was better for the EKFC (median bias closer to zero and higher P30, as judged by nonoverlapping CIs) than the CKiD equation in children and the CKD-EPI equation in young adults (18 to <40 years) and older adults (≥65 years) but not in middle-aged adults (40 to <65 years). Strengths of the current study include a large study population with a wide range of ages and mGFRs, standardized assays for SCr and acceptable methods for mGFR, and rigorous statistical evaluation. However, it also has limitations. First, the findings may not be generalizable to other populations, particularly Black people. We compared the performance of the EKFC and CKD-EPI equations in a different, large external validation population of Black and non-Black adults (Figure). Our results do not confirm the authors' conclusions. Among non-Black (mostly White) people, the EKFC equation had similar bias but a lower P30 than the CKD-EPI equation. Among Black people, the EKFC equation had a larger bias (underestimate of mGFR), whereas the CKD-EPI equation was unbiased; P30 was similar for both equations. Although the performance of both equations varied among age groups, the EKFC equation did not perform better than the CKD-EPI equation in younger adults and performed worse than the CKD-EPI in middle-aged and older adults. The reason for these differences is not well understood. Among non-Black people, the small differences in bias between equations may reflect differences in the method for measuring GFR as well as the GFR range in the development populations, whereas the large discrepanices in P30 between the equations are probably the result of differences in non-GFR determinants among younger adults in the development populations. In the Black population, the large bias of the EKFC equation is probably the result of the absence of Black participants in the EKFC development population. Thus, using this equation for Black patients would not be appropriate. Second, the study did not compare the EKFC with other equations of interest, including the