CLN - Feature

Making the Switch to Race-Free GFR Estimates

Experts say new eGFR equations lessen racial healthcare disparities and are easy to program into laboratory information systems

Eric Seaborg

A male doctor pointing at a piece of paper for a female patient sitting on a doctor bed

Laboratories around the country are dropping the race modifier in estimated glomerular filtration rate (eGFR) calculations of kidney function. They are changing to new formulas recommended by the National Kidney Foundation (NKF) and American Society of Nephrology (ASN) Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Diseases.

The new formulas for creatinine and creatinine-cystatin C equations were published by the Chronic Kidney Disease Epidemiological Collaboration (CKD-EPI) in the New England Journal of Medicine in November, 2021, and are known as CKD-EPI 2021 (and sometimes the CKD-EPI 2021 refit) equations (N Engl J Med 2021; doi: 10.1056/NEJMoa2102953).

Measuring serum creatinine for an eGFR is recommended as the first step in assessing kidney function by clinical practice guidelines. In an article published simultaneously in the Journal of the American Society of Nephrology and the American Journal of Kidney Diseases, the NKF-ASN task force recommended that all U.S. laboratories adopt the new creatinine formula “because it does not include race in the calculation and reporting, includes diversity in its development, is immediately available to all labs in the U.S., and has acceptable performance characteristics and potential consequences that do not disproportionately affect any one group of individuals.” 

The task force also recommended national efforts to facilitate increased use of cystatin C measurement as a confirmatory test because combining filtration markers provides more complete information for clinical decisions.

The use of a race multiplier—which required inputting whether a patient was “African-American or non-African-American”—in eGFR equations had come under increasing scrutiny for its lack of recognition that race is a social construct rather than a biological one. Spurred by worries that the modifier was also potentially contributing to racial disparities in access to kidney treatment, many institutions dropped it from their eGFR equations, leading to inconsistency in eGFR estimates among institutions.

Standardized Reporting

The new creatinine equation offers laboratories “a way to standardize the reporting of eGFR,” said to Greg Miller, PhD, a member of the NKF-ASN task force, a former AACC president, and professor of pathology and codirector of clinical chemistry at Virginia Commonwealth University in Richmond.

“We are hoping that we can convince laboratories that they should quickly adopt the new CKD-EPI 2021 equation, not only because it eliminates the potential racial disparity concern, but it also would make for a more consistent practice of patient management across the country,” Miller said.

Miller headed an NKF working group that published a “practical guidance” to help laboratories implement the new equations. The paper was published online in December 2021 and will appear in the print version of Clinical Chemistry in April (Clin Chem 2021; doi: 10.1093/clinchem/hvab278). The paper contains detailed recommendations on how to communicate the reasons for the change to stakeholders, how to program new parameters into laboratory information systems, and more.

Miller said that his and other institutions have already made the change. “The transition is actually surprisingly easy from an IT point of view, because the form of the new equations is the same as the form of the old equations. All you have to do is change the coefficients,” Miller told CLN.

Apparent Differences

The use of a race coefficient dates back to the Modification of Diet in Renal Disease (MDRD) study reported in 1999, in which all patients had their GFR measured by the kidney iothalamate clearance, considered a gold standard of function but not a practical test for widespread use compared with creatinine. The researchers concluded that self-identified Black individuals had higher creatinine levels vis-a-vis a given GFR, so they inserted a correction factor in the MDRD estimating equation.

In 2009, the Chronic Kidney Disease Epidemiological Collaboration did a similar study with comparable results and published the widely used CKD-EPI 2009 formulas with a similar race-based correction factor.

“At the time, this adjustment was thought to be an advancement because an important group, with high risk for CKD progression, was included in studies of measured GFR,” wrote the authors of the initial report from the NKF-ASN task force. However, the correction factors meant that if a Black and non-Black patient had the same creatinine level, the Black patient would be reported with a more favorable eGFR, and less likely to be considered for treatment.

Racial Inequities

As concerns over racial inequities in healthcare grew—as did recognition that Black individuals experienced kidney disease at higher rates than White individuals—the use of the correction factor came under increasing scrutiny.

Beth Israel Deaconess Medical Center (BIDMC) in Boston was one of the first places to act. In the spring of 2016, nephrologist Melanie Hoenig, MD, an associate professor of medicine at Harvard Medical School, was explaining the racial coefficient "when a medical student. asked pointedly, ‘Why would there be a correction factor for a healthier value for the group at greatest risk of kidney disease?’”

The question inspired Hoenig and her students to explore the literature review, engage in conversations with stakeholders at BIDMC, and conclude that “the use of race in clinical medicine is flawed and problematic. Ultimately, we agreed to change the language of the report to remove race, but we provided two values generated by the eGFR formula to try to reintroduce the notion that the formula reports an estimate.”

A handful of other institutions made similar moves—often also initiated by medical students and residents—and several articles and editorials appeared questioning the use of the race modifier. But the issue gained immediacy after the reaction to the killing of George Floyd in May 2020 took the racial justice movement to a new level.

In August 2020, the ASN and NKF formed their joint task force to reassess the use of race. The task force followed an exhaustive process that considered 26 different potential strategies suggested by a variety of experts. But the breakthrough came when the CKD-EPI Collaboration researchers went back to reanalyze the data sets they had previously used along with data from newer studies to create its updated formulas.

AACC Forms Task Force

For its part, AACC formed an eGFR and Race Equity Task Force to examine the issue. Chaired by Hoenig, the task force included individuals with expertise in clinical laboratory medicine, nephrology, primary care, pharmacy, and evidence-based medicine. They performed a systematic literature review to determine whether there was evidence “supporting the use of the Black race modifier in creatinine-based eGFR calculations.”

The task force published its findings online in December 2021, prior to appearing in the April print issue of Clinical Chemistry, and concluded: “There is little evidence supporting the inclusion of a race modifier in eGFR calculations. Although the use of the Black race modifier may have improved the accuracy of the formula in the original population studies, the Black race modifier does not demonstrate any analytical or clinical benefit in clinical diagnoses and treatment for an individual patient, and rather may contribute to healthcare inequities and social harms” (Clin Chem 2021; doi: 10.1093/clinchem/hvab279).

Hoenig said that this work was different from but complementary to the work of the NKF-ASN task force: “I think it was important for AACC to have its own look at this issue. This is the first time all these papers have been put together. The formulas have been used for decades, so it is important to take a really hard look and say, ‘What is the evidence?’”

Hoenig’s institution changed to the formulas recommended by the NKF-ASN task force in mid-February.

Labs Implement the Change

Lakshmi V. Ramanathan, PhD, service chief of the clinical chemistry service, attending chemist, and director of point-of-care testing at Memorial Sloan-Kettering Cancer Center in New York City, said that her institution has already made the change.

As a member of the NKF laboratory engagement group, she was already aware of the issue, but
waited until the new formulas were published in the New England Journal of Medicine to act.

“Once the equations were available, we had a discussion with our nephrologists, and they agreed that we should go forward,” Ramanathan said. “There was a lot of work that our computer staff had to do to make sure the equation was right. We did a lot of cross checks for accuracy. Then on a Sunday, when it was a little quiet, the computer systems upgraded with the new equations.”

Laboratory medicine and renal medicine sent an email notifying physicians about the new equation, and the transition went smoothly. “We have had no real pushback or any questions,” Ramanathan said.

Many large institutions, including the Johns Hopkins Health System, University of Maryland Schol of Medicine, and Oregon Health & Science University, announced the switch to the new formulas on their websites.

Miller said that his institution was coincidentally implementing a new computer system, so it was just a matter of incorporating the new equations into the new computer system. “It was a relatively easy transition,” he said. “I have talked to colleagues at other institutions that have already switched to the new equation, and they have reported the same thing, that everybody was receptive to the change and just started using the new equation. It has just seemed like the right thing to do.”

Miller hopes that the focus on the CKD-EPI 2021 equation can bring order to a rather chaotic current approach to eGFRs. The Clinical Chemistry guidance article notes: “In a 2019 survey by the College of American Pathologists, 23% of 6,200 laboratories reporting eGFR-creatinine used an incorrect equation that is not suitable for use with standardized creatinine measurements, 34% used the CKD-EPI 2009 equation, and 43% used the MDRD Study 2006 equation re-expressed for standardized creatinine measurement.”

The new CKD-EPI 2021 equation offers an opportunity for laboratories to standardize to the most up-to-date practice, as well as to take a step toward lessening racial disparities in healthcare, Miller said.

Eric Seaborg is a freelance writer in Charlottesville, Virginia.+Email: [email protected]