investigating the SDMA approach. “However, these markers are also imperfect and have their own limitations,” he acknowledged.
Experts have grappled with the race corrector issue for some time. In precision medicine, “we expect medicine to work with precise quantities that are clearly defined and precisely measured,” said Jay Kaufman, PhD, a professor at McGill University’s department of epidemiology, biostatistics, and occupational health. None of this is true for race, he told CLN Stat.
With no blood or genetic test that reveals someone’s true race, healthcare practitioners rely on patients’ self-reporting their racial backgrounds, whose accuracy and reliability have no definition, Kaufman said. “This is an impossible situation, and we would never allow this for any other variable in medicine. Is a person with ancestry from Ethiopia Black? How about Sudan? Egypt? Mali? Madagascar? Or how about someone with ancestry from Colombia? Brazil? Puerto Rico? Do we judge this just by looking at the person, and if so, what traits are we looking for and why, and what is the inter-rater reliability?”
Most U.S. labs use the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) or Modification of Diet in Renal Disease (MDRD) equations for estimated GFR. These incorporate the race correction factor, also known as the African American coefficient. Developers based this algorithm on evidence that Black people have higher-than-average serum creatinine concentrations, wrote Darshali A. Vyas, MD, Leo G. Eisenstein, MD, and David S. Jones, MD, PhD, in the New England Journal of Medicine. The assumption is that Black people are more muscular, releasing more creatinine into their blood at baseline.
Michelle Morse, MD, MPH, previously told CLN Stat that the race corrector was based on poor quality studies and does not reflect self-identification of race. As a result, black people might not be getting optimal kidney care.
Using sex and race in eGFR equations in a world that is more than just males or females, and Black or not, is problematic, observed El-Khoury. “How do you calculate eGFR on individuals who are transgender, have ambiguous genitalia, are mixed race, or simply refuse to identify either sex or race (or both)? The decision is not trivial and can have significant consequences on the care they receive for their kidneys, from missing the diagnosis to early referral to nephrology, dialysis, and/or kidney transplantation.”
It may not be so easy to eliminate this metric from the CKD-EPI equation. Andrew S. Levey, MD, and colleagues tested this approach in more than 8,500 patients, using a revised formula that substituted height and weight for race. The new approach led to more errors in the evaluation of African American individuals, not to mention worse performance in this population. Eliminating race from the equation could therefore have unintended consequences for African American individuals, such as inappropriate early transplant or dialysis initiation, CKD overdiagnosis, or inadequate drug dosing, Levey and colleagues wrote in a letter to the Journal of the American Medical Association (JAMA).
Laboratorians debated the issue in a recent AACC Artery conversation. “There is no scientific evidence for a racial contribution to the measured GFR,” wrote Chris Wunsch, MD, PhD. “The African-American factor found in the United States represents a socioeconomic group, not race.” Readers can type in “full age spectrum equations” in PubMed to find superior or equal alternatives to the MDRD and CKD-EPI equations, Wunsch suggested. Age and gender are both essential factors, he later told CLN Stat. Frank Hall, PhD, DABCC, FADLM, questioned whether its removal would be in the patients’ best interest. “What reference interval would work for all? If this is being done mainly for political correctness, will gender reference ranges be questioned next?” Hall added that he’d support its elimination if it was based on sound science.
How institutions apply these equations and corrections lacks consistency, noted Kaufman. Some institutions might arbitrarily apply the MDRD equation and others the CKD-EPI equation, “even though the race correction is twice as large in the former compared to the latter,” he said.
The National Kidney Foundation and American Society of Nephrology recently launched a task force to look at the race-based adjustment. Similarly, AACC’s Science and Practice Core Committee (SPCC) is in the process of creating a working group to address the race corrector and any follow-up plans SPCC/AACC should consider. The panel has reached out to AACC membership and plans to bring a core group of thought leaders together to determine next steps on addressing racial inequities with the eGFR formula, said Stacy Melanson, MD, PhD, SPCC chair. “This will include the generation of key questions that need to be answered to help laboratories more effectively serve clinicians and patients. We are also exploring a collaboration with the National Kidney Foundation to develop guidelines for laboratories,” said Melanson, associate director of clinical laboratories at Brigham and Women’s Hospital in Boston.
Institutions such as the University of Washington, Massachusetts General Hospital, and Brigham and Women’s Hospital move to eliminate race-based reporting of kidney function from their practices, Meanwhile, more than 700 University of California San Francisco (UCSF) and San Francisco General Hospital (SFGH) physicians in a petition are calling for SGFH, San Francisco Department of Public Health, and affiliated UCSF Medical Centers’ laboratories to permanently remove race from eGFR reporting and replace it with a single result based upon the CKD-EPI equation with creatinine, age, and sex. One of the petitioners, Neil Powe, MD, MPH, MBA, chief of medicine at SFGH and professor of medicine at UCSF, recently wrote about the eGFR race corrector controversy and discussed it with Howard Bauchner, MD, editor-in-chief of JAMA.
An uneven move by organizations to eliminate the race-based correction factor could further exacerbate harmonization struggles related to eGFR reporting, said El-Khoury. This is why additional oversight and guidance is desperately needed in this space, he added. “Until then, it is very important that every organization specifies the assay and equation used to generate the eGFR value included in each patient’s report.”
Clinical validation should take place at each testing site to ensure that the equation performs similar to published studies using the institution’s own assay and population. “In addition, performing actual GFR measurement instead of estimating it by equations should be considered when making important decisions like transplant referrals,” recommended El-Khoury.
Studies are underway to evaluate the impact of eliminating the African American coefficient in the estimating equations, Greg Miller, PhD, professor of pathology and co-director of clinical chemistry at Virginia Commonwealth University, told CLN Stat. “The end points to consider include the number of people who would be reclassified to a different risk category (or classification of severity of CKD) and what difference that reclassification would make in treatment or in eligibility for transplant,” he noted.
Removing this coefficient produces a lower eGFR that is more biased to measured GFR. This shift will lead to more people who self-declare as African American to be eligible for transplants, Miller said. However, “it will also cause the same group to be classified as having more severe CKD,” leading to lower and less effective drug doses, he added.
Labs are central to this discussion and should have a role in the decision-making process, El-Khoury emphasized. “Laboratory professionals are the experts when it comes to the validation of assays and associated equations used in our labs. Our input is vital,” he said. Clinical teams deciding on the best approach may not be aware of a possible lack of concordance between certain assays used in the reported literature and the one used in their lab, leading to use of the wrong equation. “In addition, laboratory professionals will need to be involved with educating clinical teams on the limitations of their markers and assays, as well as leading the development of guidelines and regulations to harmonize results between different organizations,” he stressed.
Reliance on something as crude as “race” is simply outdated in the 21st century, concluded Kaufman. “People are much more than their skin color.”