The European Kidney Function Consortium (EKFC) has developed a new race- and sex-free cystatin C-based equation to estimate glomerular filtration rate (GFR) that appears more accurate than the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) cystatin C equation.

Cystatin C is produced by all nucleated cells and is freely filtered at the glomerulus.

Hans Pottel, PhD, of the Department of Public Health and Primary Care in Kortrijk, Belgium, and colleagues used data from 227,643 patients in Sweden to estimate a rescaling factor for the cystatin C level in adults that did not differ by race or sex. The rescaling factor for cystatin C was estimated at 0.83 mg/L for men and women younger than 50 years, with 0.005×(age – 50) added for men and women aged 50 years or older. The rescaling factor was based on analyses showing that cystatin C levels did not differ between White and Black patients who had the same age, sex, body mass index, and measured GFR.

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After incorporating the rescaling factor into their cystatin C equation for estimating GFR, the investigators validated the new equation among 11,231 patients from Europe, 1093 from the United States, and 508 from Africa. Using measured GFR as the standard, the EKFC cystatin C equation performed somewhat better than the race-free 2021 CKD-EPI cystatin C equation, according to results published in the New England Journal of Medicine.

As previous studies have demonstrated, the EKFC cystatin C-based equation did not have better accuracy in estimating measured GFR compared with the EKFC serum creatinine-based equation. Estimated GFR was more accurate when both cystatin C and serum creatinine filtration markers were included in the equation, Dr Pottel’s team pointed out.

The National Kidney Foundation and the American Society of Nephrology Task Force has recommended “increased, routine, and timely use of cystatin C.” Cystatin C testing and eGFR may clarify CKD staging, according to a recent report published in Kidney360. Unlike serum creatinine levels, cystatin C levels are less dependent on muscle mass, dietary protein, and frailty. Therefore cystatin C eGFR may be more accurate in some patients, such as those who are older, inactive, and diagnosed with cancer. Cystatin C levels are affected by steroid use, thyroid dysfunction, adiposity, and inflammation.

Disclosure: This research was supported by the Swedish Research Council. Please see the original reference for a full list of disclosures.


Pottel H, Björk J, Rule AD, et al. Cystatin C-based equation to estimate GFR without the inclusion of race and sex. N Engl J Med 388:333-343. Published online January 26, 2023. doi:10.1056/NEJMoa2203769

Delgado C, Baweja M, Crews DC, et al. A unifying approach for GFR estimation: Recommendations of the NKF-ASN Task Force on reassessing the inclusion of race in diagnosing kidney disease. J Am Soc Nephrol 32(12):2994-3015. doi:10.1681/ASN.2021070988

Chen DC, Potok AO, Rifkin D, Estrella MM. Advantages, limitations, and clinical considerations in using cystatin C to estimate GFR. Kidney360 3:1807-1814. doi:10.34067/KID.0003202022