As medical institutions around the country intensify efforts to eliminate structural racism from their systems and practices, UC San Francisco faculty have been at the forefront of this pursuit in kidney medicine.
In late September, a task force co-chaired by UCSF faculty released eagerly awaited recommendations to remove a race modifier from an equation that estimates kidney function. Those recommendations incorporated research by other UCSF faculty into how best to calculate kidney function without using race. The movement for race-free medicine, in nephrology and beyond, was spurred by activism from medical students, residents and faculty at UCSF and other institutions. It also helped inspire UCSF Health to remove race in estimates of kidney function.
“I give a lot of credit to the activists who pushed us and who don’t always get the academic recognition. They stimulated thinking in a way that was very valuable,” said Chi-yuan Hsu, MD, professor of medicine and chief of the Division of Nephrology at UCSF Health, whose research on a new approach using cystatin C to estimate kidney function without race was published last week in the New England Journal of Medicine. “And the task force, of course. They took a lot of heat and didn’t have an easy job. Their recommendations are well-considered and reasonable.”
Race and eGFR
At issue is an algorithm for estimated glomerular filtration rate, or eGFR, which is used to diagnose and capture the severity of chronic kidney disease. Since 1999, the most common eGFR equations used blood creatinine levels, sex, age – and Black or non-Black race. That’s because studies found creatinine levels were higher in people who self-reported as Black, even when their actual measured kidney function was the same as non-Black persons with lower creatinine levels.
For many people, an adjustment for Black persons perpetuates harmful notions that race is a biological construct instead of a social one, said Neil Powe, MD, Constance B. Wofsy Distinguished Professor and Vice Chair of Medicine at UCSF and Chief of Medicine at the Priscilla Chan and Mark Zuckerberg San Francisco General Hospital. Powe co-chaired the National Kidney Foundation-American Society of Nephrology Task Force that issued the new recommendations.
“It’s now morally wrong to include race in the eGFR equation when there is an adequate replacement,” Powe said. “The new equation we recommend for first-line testing removes it and was developed in a diverse study population with African-Americans well represented.”
In addition to being equitable and patient centered, the new task force recommendations needed to be easy to adapt and to implement consistently by medical institutions and facilities across the nation, said Cynthia Delgado, MD, associate professor of medicine and nephrology at UCSF, who co-chaired the task force with Powe.
“We needed an approach that can be implemented across the country. We really don’t want our patients to go to one institution and be told they have chronic kidney disease using one approach, then move across the country and see a different provider who tells them something else because they have a different method of measuring eGFR,” Delgado said.
Many medical institutions changed their practices while awaiting final guidance from the task force. In October 2020, UCSF Health changed to showing two eGFR estimates but not reporting the two results as being associated with a particular race.
“We took the race labels off because it was not appropriate, and it was part of a perpetuation of race as a biological rather than social construct,” said Joshua Adler, MD, Executive Vice President for Physician Services at UCSF Health and Vice Dean for Clinical Affairs at UCSF Medical School. “We also used the change as an opportunity to advise health care providers that eGFR results are estimates of kidney function and that there are multiple factors that influence the accuracy of these estimates in individual patients.”
A Role for Cystatin C
While it was critical to remove race from the equation, the task force decided it was best to introduce changes slowly and start with a new eGFR equation that continued using creatinine, because it has been standardized in the last 10 years and is frequently ordered as part of a comprehensive metabolic panel.
“Creatinine is ubiquitous; it’s available in every hospital and clinic throughout the U.S. One could turn the switch very quickly with the new equation, because it just requires programming it into the computer,” Powe said. “That was part of the rationale for the recommendation.”
The task force said clinicians who need more information after the first-line test with creatinine should order tests for cystatin C, the alternative marker that Hsu has studied. The task force said equations with both markers provide a better indication of kidney function than either marker alone.
The research on the recommended first-line creatinine equation and combined creatinine-cystatin C equation was published in the New England Journal of Medicine and included co-authors Michelle Estrella, MD, and Michael Shlipak, MD, both UCSF professors of medicine and members of the Kidney Health Research Collaborative.
Hsu’s study, which published in the same issue and included UCSF co-authors Anthony Muiru, MD, assistant professor, and Alan Go, MD, adjunct clinical professor, also supported the value of cystatin C in measuring eGFR, but recommended using it alone without creatinine.
“Our study tried to get rid of race in the eGFR equation in three ways: replace it with genetic ancestry, which worked, but it’s not feasible to go around genotyping everyone in clinical practice. Second, we tried replacing with things that affect creatinine like muscle mass and diet, but that did not get rid of the race coefficient. Third was to replace creatinine with cystatin C, which was just as accurate as creatinine with the race coefficient,” Hsu said.
Balancing Accuracy, Equity and Practicality
There are some practical barriers to estimating kidney function with cystatin C, however, because the test is not widely available, takes longer and costs more than the test for creatinine, but Hsu said this could be overcome if more providers began to use cystatin C.
“It’s a vicious cycle – if there isn’t demand, there is less incentive to optimize it, which in turn will suppress demand,” Hsu said. “My feeling is we should just do a big push toward optimizing and using cystatin C. There is something about creatinine and race that we just don’t fully understand.”
One notable argument against removing race by simply dropping the “race coefficient” from the old creatinine equations, as some non-UCSF institutions did, was that while the result might qualify more Black patients for transplantation and specialist referral, it could also affect whether Black patients meet requirements for dosing of certain drugs, use of contrast dyes for imaging, and enrollment in clinical trials. That tradeoff will likely exist with the recommended new equation, Powe said, but to a much lesser extent.
“The kidney function test is a very routine screen, and it has penetrated all aspects of medical care. The effects of this are going to reach beyond the practice of nephrology or primary care, because you are talking about changes in drug dosing, and considerations for folks getting cardiac catheterization, CAT scans, or MRI,” Delgado said.
Beyond nephrology, UCSF Health is evaluating other diagnostic tests that are known to utilize race in the calculation of results, among them pulmonary function and bone density tests. Said Adler, “More work is needed and underway in both areas to determine how best to remove inappropriate uses of race in these calculations.”
The University of California, San Francisco (UCSF) is exclusively focused on the health sciences and is dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. UCSF Health, which serves as UCSF’s primary academic medical center, includes top-ranked specialty hospitals and other clinical programs, and has affiliations throughout the Bay Area.