Study suggests alternative to race-based kidney-function calculations

Sept. 24, 2021

Researchers have proposed changing a key measure in kidney disease diagnosis and treatment to eliminate the use of race as a variable. The goal is to provide a non-biased kidney function test that does not compromise accuracy, according to a news release from the National Institutes of Health (NIH), which supported the study.

The study suggests use of a blood lab test called cystatin C, which does not vary by a person's race, to replace the current lab test called creatinine, which does. The findings come from a detailed analysis of data from the Chronic Renal Insufficiency Cohort (CRIC) Study, a nationwide longstanding study funded by NIH's National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).

The results are published in the New England Journal of Medicine.

Healthcare providers use estimated glomerular filtration rate, or eGFR, calculations as a primary diagnostic tool to learn how well a person's kidneys function and to classify the severity of their disease, from mild loss of kidney function to end-stage kidney disease. The eGFR helps determine prognosis and treatment, such as when hemodialysis or a transplant may be needed.

Since 1999, race has been a variable used in estimating GFR. Current eGFR calculations also use a person's age, sex, and serum creatinine levels. Serum creatinine, which the kidneys filter out, is a waste product from the normal metabolism of muscle cells in one's body. Studies have shown that Black Americans, on average, can have higher levels of serum creatinine in their blood, independent of kidney function. To account for this difference, eGFR calculations include a person's self-reported race to give more valid results.

"Using race as a testing factor risks kidney disease misdiagnosis. There is great variance within the genetic ancestry of people who identify as 'Black' which means we cannot reliably view 'Black' people as being from a single ancestral group," said Afshin Parsa, MD, NIDDK program director for CRIC. "Misdiagnosis could lead to a person receiving incorrect drug dosing, or delays in receiving dialysis or a kidney transplant. Current eGFR calculations could be exacerbating racial inequities in a disease that disproportionately affects Black people, so this study set out to identify factors that wouldn't rely on including a person's race to calculate eGFR."

CRIC researchers found that even when adjusting for a wide range of factors, using serum creatinine to calculate eGFR without using a race term can lead to systematic bias and race-related misclassification of kidney disease status in people tested.

Yet, unlike serum creatinine, most biomarkers — substances that can help identify disease or stages of a disorder — aren't affected by race or ancestry. By analyzing data from CRIC participants, the researchers found that using cystatin C — which is not affected by race or ancestry — as a race-independent replacement biomarker for serum creatinine provided accurate and non-biased results.

"We hope this study's results will build momentum toward widespread adoption of cystatin C for the purposes of estimating GFR. The alternative eGFR test requires no special equipment, can be standardized, and the more it's adopted, the less it would cost," said Chi-yuan Hsu, M.D., Professor and Chief of nephrology at University of California, San Francisco, and lead author of the study.

CRIC is one of the largest and longest-running studies looking at the causes, frequency, and consequences of chronic kidney disease, or CKD, in the United States. Nearly all CRIC's participants are people with mild to severe loss of kidney function. Since Black people are at higher risk for CKD than other groups, approximately half of CRIC participants are Black. This analysis used more than 1,200 CRIC participants' data, including measures of body mass and muscle mass, genetic ancestry data, and self-identified race.

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