All laboratories in the United States should immediately remove the race modifier when using the Chronic Kidney Disease-Epidemiology (CKD-EPI) equation to determine estimated glomerular filtration rate (eGFR), a joint task force of the National Kidney Foundation (NKF) and the American Society of Nephrology (ASN) recently announced.
The widely used Chronic Kidney Disease-Epidemiology (CKD-EPI) equation published in 2009 includes a race-based modifier that may lead to inaccurately high GFR estimates in patients who self-identify as Black. The task force is recommending the immediate adoption of a new 2021 CKD-EPI creatinine eGFR equation that has been refit to estimate kidney function without a race variable. An updated eGFR calculator using this equation is available online. The task force's recommendation was part of a final report reassessing the inclusion of race in diagnosing kidney disease, which was based on expert testimony; social and scientific evidence; oral testimonies from patients, clinicians, and trainees; and community feedback.
The task force also recommended national efforts to facilitate increased, routine, and timely use of cystatin C, especially to confirm eGFR in adults who are at risk for or have chronic kidney disease. Combining filtration markers (creatinine and cystatin C) is more accurate and informs clinical decision making better than either marker alone, the task force said. “If ongoing evidence supports acceptable performance, the CKD-EPI eGFRcystatin C (eGFRcys) and eGFR creatinine-cystatin C (eGFRcr-cys_R) refit without the race variables should be adopted to provide another first line test in addition to confirmatory testing,” the report said.
Finally, the task force recommended encouragement of research and additional funding on GFR estimation with new endogenous filtration markers, as well as interventions to eliminate race and ethnic disparities. “An investment in science is needed for newer approaches that generate accurate, unbiased, and precise GFR measurement and estimation without the inclusion of race, and that promote health equity and do not generate disparate care,” the task force authors wrote. The report was published Sept. 23 in the Journal of the American Society of Nephrology and the American Journal of Kidney Diseases.
Supporting evidence for the use of cystatin C in eGFR equations was provided by two new studies published by the New England Journal of Medicine on Sept. 23. The first study used data from 23 studies to develop new eGFR equations that did not include race and a set of 12 studies as a validation set to compare the new equations with each other and the current race- and creatinine-based one. They found that the current equation overestimated eGFR in Black patients (and, to a lesser degree, non-Black patients), but that a creatinine-based equation omitting race underestimated GFR in Black patients and overestimated it in non-Black patients. An equation that incorporated both creatinine and cystatin C but omitted race was more accurate and led to smaller differences between Black participants and non-Black participants than an equation based on either biomarker alone. All of the new equations fell within the 30% margin of error, but the inaccuracies found in the creatinine-only equations “could lead to systematic differences in care between race groups, especially at higher GFR,” the authors said.
The second study used data from 1,248 chronic kidney disease patients to assess the accuracy of eGFR equations. It found that for Black patients, simply omitting race resulted in more underestimation of GFR than the current method and that inclusion of non-GFR determinants of the serum creatinine level (e.g., body composition metrics and urinary excretion of creatinine) did not eliminate the misclassification. However, the use of cystatin C “generated similar results while eliminating the negative consequences of the current race-based approaches,” the authors said. “Challenges regarding the cost, calibration, and standardization of cystatin C measurements would have to be addressed, but we anticipate that cost reduction could occur with broad adoption over time.”
An accompanying editorial noted that all GFR estimates are imperfect and that equations using cystatin C, while promising, will take time to implement, since this variable is not routinely or uniformly measured. “Both existing and newly derived equations have strengths and weaknesses, and change inevitably induces unanticipated consequences,” the editorialists wrote. “Most important, however, is that estimates do no harm but rather help us care for all patients equally.”
ACP Hospitalist described problems with the use of race in clinical algorithms in January (ACP membership and login required).