Cystatin C test grants alternative to creatinine for race-free kidney function assessments
Research from Kaiser Permanente supports the use of cystatin C tests as an alternative to creatinine-based tests for accurately assessing kidney function without the inclusion of race.
The study was released on the date that the National Kidney Foundation-American Society of Nephrology (NKF-ASN) joint task force urged the immediate adoption of race-free eGFR equations.
In a related press release, investigators from Kaiser Permanente indicated their findings may inform further NKF-ASN guideline recommendations on the evaluation of kidney function.
Blood cystatin C test vs blood creatinine test
“Our research showed that if you use a blood cystatin C test, instead of a blood creatinine test, you don’t need to include race to get a similarly accurate estimate of kidney function,” Alan S. Go, MD, a senior research scientist at the Kaiser Permanente division of research in Northern California, said in the release.
Co-lead author of the study, Chi-yuan Hsu, MD, a nephrologist at the University of California, San Francisco and an adjunct investigator with the Kaiser Permanente Division of Research, said, “Cystatin C solves the scientific problem of maintaining comparable accuracy and it achieves the social and scientific goal of getting rid of the need to consider race.”
To investigate methods for estimating GFR without including race, researchers analyzed data collected from 1,248 adults with chronic kidney disease. Assessed factors included race as reported by the participant, genetic ancestry markers, serum creatinine, serum cystatin C and 24-hour urinary creatinine levels. Researchers considered three alternatives to current GFR estimations.
“First, we examined whether we could replace race with a quantitative measure of genetic ancestry in GFR estimation. Second, we evaluated whether we could replace race in GFR estimation by accounting for determinants of serum creatinine that are unrelated to GFR and that vary according to race. Third, we assessed whether we could eliminate the need to consider race – and genetic ancestry, given findings from our first set of analyses – in GFR estimation by replacing the use of serum creatinine with serum cystatin C as the glomerular filtration marker,” the researchers wrote.
Findings showed that when using current formulations of GFR estimating equations in participants who identified as Black, a model that omitted race resulted in more underestimation of GFR (median difference between measured and estimated GFR was 3.99 mL per minute per 1.73 m2 of body-surface area) and lower accuracy compared with models that included race (median difference was 1.11 mL per minute per 1.73 m2).
Similarly, researchers observed that incorporating genetic ancestry data instead of race resulted in more underestimation of GFR and lower accuracy than the models that included race (median difference was 1.33 mL per minute per 1.73 m2).
“The inclusion of non-GFR determinants of the serum creatinine level (eg, body-composition metrics and urinary excretion of creatinine) that differed according to race reported by the participants and genetic ancestry did not eliminate the misclassification introduced by removing race (or ancestry) from serum creatinine-based GFR estimating equations,” the researchers wrote.
Race, genetic ancestry not necessary
However, when estimating GFR with the use of cystatin C, findings revealed incorporation of race or genetic ancestry was not necessary to achieve “similarly statistically unbiased and accurate estimates in Black participants” (median difference was 0.33 mL per minute per 1.73 m2).
“Our results show that race and genetic ancestry are linked to a person’s creatinine level, and we can’t erase that even if we account for a wide range of other factors, such as muscle mass, dietary protein intake, and other factors that are believed to influence blood creatinine level independent of kidney function,” Go said. “We believe that changing to the cystatin C test will promote more equity for people of all racial and ethnic backgrounds.”
The most recent recommendations by the NKF-ASN task force suggest all laboratories in the United States begin using the CKD-epidemiology collaboration creatinine equation without including race, as well as increasing the use of cystatin C and combining creatinine and cystatin C markers to gain more accurate assessments of kidney function.
- Hsu C, et al. New England J Med. 2021;doi:10.1056/NEJMoa2103753.
- Kaiser Permanente: Alternative to using race in kidney function test found. https://www.eurekalert.org/news-releases/929354. Published Sept. 23, 2021. Accessed Sept. 27, 2021.