Race-Free GFR Equations Based on Creatinine Plus Cystatin C More Accurate

multiracial group
The current guideline-recommended creatinine-based eGFR equation incorporates a race coefficient that may overestimate eGFR in Black adults and contribute to discordant care.

Among equations for estimating glomerular filtration rate (GFR), a new race-free version of the creatinine-cystatin C GFR equation most closely approximates measured GFR, investigators reported on September 23 in The New England Journal of Medicine.

Inclusion of race in GFR estimating equations has been under scrutiny because race is a social and not a biologic construct. “National kidney disease organizations recommend replacement of current eGFR equations by equations that do not use race and that are accurate, inclusive, and standardized in every laboratory in the United States,” Lesley A. Inker, MD, MS, director of the Kidney Function and Evaluation Center at Tufts Medical Center in Boston, Massachusetts, and colleagues stated.

Toward that goal, the investigators first evaluated the accuracy of the 3 current kidney function estimating equations based on the filtration markers serum creatinine (cr) and cystatin C (cys) that were developed by the CKD-EPI research group. All of the equations incorporate age and sex. Black race is also a variable in the current eGFRcr and eGFRcr-cys equations but not in the current eGFRcys equation. The investigators used a validation data set of 12 studies including 4050 patients, of whom 14.3% were Black, to compare estimated and measured GFR using the various equations.

According to the validation data set, the current, widely-used creatinine equation that incorporates age, sex, and race overestimated measured GFR (in mL/min/1.73 m2) in Black patients by a median 3.7 and in non-Black patients by a median 0.5. Omitting the Black race coefficient underestimated measured GFR in Black patients by a median 7.1. A new race-free equation based on creatinine also underestimated measured GFR in Black patients by a median 3.6, whereas it overestimated measured GFR in non-Black patients by a median 3.9.

The current race-based eGFRcr-cys equation overestimated measured GFR in Black adults by 2.5 and overestimated measured GFR in non-Black adults by 0.6, according to the investigators. Using the non-Black version of the eGFRcr-cys equation underestimated measured GFR in Black adults by 3.4 and overestimated measured GFR in non-Black adults by 0.6. The new race-free creatinine-cystatin C estimating equation underestimated measured GFR in Black adults by 0.1 and overestimated measured GFR in non-Black adults by 2.9.

For all equations, 85% or more of the estimated GFRs were within 30% of measured GFR for Black and non-Black adults. The current equations based on creatinine, cystatin, or both filtration markers displayed shortcomings in their percentage of agreement with measured GFR and the movement of patients across clinically significant eGFR categories (ie, chronic kidney disease [CKD] stage). The new eGFRcr-cys equations minimized overdiagnosis and underdiagnosis the most.

Dr Inker’s team said the “new eGFRcr-cys equations minimized inaccuracy for both race groups, differences in eGFR between race groups, and differences in estimated CKD prevalence. More frequent use of [the new] eGFRcr-cys may improve the accuracy of CKD diagnosis and GFR staging while eliminating the use of race in GFR estimating equations.”

Study limitations included a lack of representation of racial and ethnic groups other than Black and White and the omission of patients with serious comorbidities in acute care settings.

Also on September 23, the National Kidney Foundation (NKF) and the American Society of Nephrology (ASN) Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Diseases announced its final report recommending adoption of a new 2021 CKD-EPI creatinine equation that estimates kidney function without a race variable. The task force also recommended increased use of cystatin C combined with serum creatinine, as a confirmatory assessment of GFR.

“The NKF and ASN urge all laboratories and healthcare systems nationwide to adopt this new approach as rapidly as possible so that we can move towards a consistent method of diagnosing kidney diseases that is independent of race,” NKF president Paul M. Palevsky, MD, said in a joint press release.

“By recommending the CKD-EPI creatinine equation refit without the race variable, the task force has taken action and demonstrated how nephrology continues to lead the way in promoting health care justice,” ASN President Susan E. Quaggin, MD, said in the same release. “It is time for other medical specialties to follow our lead, and NKF and ASN stand ready to help however we can.”

The final report is available online in the American Journal of Kidney Diseases and Journal of the American Society of Nephrology.


  1. Inker LA, Eneanya ND, Coresh J, et al. New creatinine- and cystatin C-based equations to estimate GFR without race. N Engl J Med. Published online September 23, 2021. doi:10.1056/NEJMoa2102953
  2. National Kidney Foundation and the American Society of Nephrology Release New Way to Diagnose Kidney Diseases [press release]. NKF and ASN; September 23, 2021.

This article originally appeared on Renal and Urology News