Cystatin C improves accuracy in calculations of Black patients' kidney function

Equations to estimate glomerular filtration rate more accurately predict risk of kidney failure and mortality in Black patients if they include both creatinine and cystatin C, but not race, according to a new retrospective study.

Clinicians should include cystatin C in calculations of estimated glomerular filtration rate (eGFR) to provide the most accurate risk prediction without the use of race, a recent study found.

The retrospective analysis used data from 62,011 U.S. patients (20,773 Black and 41,238 non-Black; mean age, 63 years; 53% women) to compare eGFR calculations using four standardized equations: eGFR based on creatinine and race, eGFR based on creatinine without regard to race, eGFR based on cystatin C without race, and eGFR based on both creatinine and cystatin C but without race. They compared these calculations on outcomes of kidney failure with replacement therapy and mortality from 1988 to 2018. Results were published by JAMA on June 6.

The prevalence ratio of eGFR less than 60 mL/min/1.73 m2 in Black versus non-Black participants was 0.98 (95% CI, 0.93 to 1.03; 11% vs. 12%) for eGFR including creatinine and race, 0.95 (95% CI, 0.91 to 0.98; 17% vs. 18%) for eGFR including cystatin C, and 1.2 (95% CI, 1.2 to 1.3; 13% vs. 11%) for eGFR with both biomarkers. For eGFR including creatinine but not race or cystatin C, the ratio was 1.8 (95% CI, 1.7 to 1.8; 15% vs. 9%).

During a mean follow-up of 13 years, 8% and 4% of Black and non-Black participants experienced kidney failure and 34% and 39% died, respectively. Decreased eGFR according to any of the equations was associated with significantly greater risk of both outcomes. At an eGFR of 60 mL/min/1.73 m2, the hazard ratios for kidney failure in Black patients versus non-Black patients were 2.8 (95% CI, 1.6 to 4.9) for eGFR with creatinine and race, 3.0 (95% CI, 1.5 to 5.8) for eGFR with only cystatin C, and 2.8 (95% CI, 1.4 to 5.4) for eGFR with creatinine and cystatin C, compared to 1.3 (95% CI, 0.8 to 2.1) for eGFR with creatinine but not race or cystatin C.

The results demonstrate racial differences in the risk of kidney failure with replacement therapy and mortality throughout the range of eGFR and indicate that it may be preferable to use the eGFR equation with cystatin C and creatinine which does not include race, according to the study authors.

Overall, the findings support recent recommendations that clinical laboratories implement the 2021 CKD-EPI creatinine equation without race “because creatinine remains the dominant filtration marker for estimating GFR and this equation discriminates risk well within each racial group,” the authors said. “However, data presented here showed that adding cystatin C to the eGFR equation without race is necessary to estimate racial difference in risk and improve accuracy at the individual patient level,” they added.

An accompanying editorial noted the practical problem that the most accurate equation “is not yet widely available because cystatin C measurement has not been broadly adopted across US health systems or laboratories or standardized for global use, in part because of its significantly higher cost (approximately $18.50 compared with serum creatinine measurement at approximately $5.10).” The editorialists called for “comprehensive, steadfast, and coordinated improvements in health care delivery, societal structures, and policies” to remedy this and other racial inequities.

A January 2021 ACP Hospitalist article discussed the problems with using race in clinical algorithms, including eGFR. It was a finalist for the 2022 NIHCM Foundation Health Care Trade Journalism Award.