Importance of Creatinine Generation Rate in Estimating Glomerular Filtration Rate

Assessment of glomerular filtration rate (GFR) is commonly based on serum creatinine levels. It is well-established that, for a given GFR, the mean serum creatinine level is higher in Black individuals than in non-Black individuals. Failure to account for this difference in creatinine-based GFR estimation equations leads to inaccuracies in GFR estimates for Black individuals. This higher mean serum creatinine level in Black individuals has been attributed to greater muscle mass, though this explanation remains debated. In this article, we provide mathematical proof showing that the higher mean serum creatinine level in Black individuals reflects the "net" creatinine generation rate after accounting for renal tubular secretion of creatinine and extrarenal creatinine elimination. To accurately estimate GFR, this "net" creatinine generation rate must be considered. By rescaling serum creatinine to account for the differences in creatinine production rates between Black and non-Black populations, the population-specific creatinine-based European Kidney Function Consortium (EKFC) equation provides a more accurate GFR estimate than the current Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI 2021) equation.