Dual-Biomarker Approach Best for Equitable Kidney Disease Risk Assessment, New Data Find

A widely adopted race-free equation for estimating kidney function may underestimate the risk of kidney failure and death in Black adults, according to a new analysis published in JAMA.1

The study found that while all equations showed declining kidney function was linked to worse outcomes, the commonly used creatinine-only equation without race significantly reduced or eliminated observed racial disparities, potentially obscuring higher risk in Black individuals. In contrast, equations that included both creatinine and cystatin C preserved these risk differences, suggesting they may offer a more accurate and equitable assessment.

Study questions accuracy of new kidney function equation for Black patients.

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The retrospective analysis included 62,000 adults in 8 US-based cohorts between 1988 and 2018 and aimed to determine whether different equations for estimated glomerular filtration rate (eGFR) produce different assessments of risk for kidney failure requiring replacement therapy (KFRT) and mortality in Black vs non-Black populations.

For decades, standard eGFR equations included a modifier for Black race based on the assumption that average creatinine levels differed due to muscle mass. However, race-based adjustments have come under scrutiny for perpetuating disparities and lacking a biological basis. In response, new race-free eGFR equations have been adopted widely, but little was known about how well these new equations track differences in outcomes across racial groups.

The disproportionate burden of chronic kidney disease (CKD) that falls on Black adults, who account for just 12% of the US population but are projected to make up nearly a quarter of future kidney failure cases, has been well-documented.2 A recent analysis found that population-wide CKD screening starting at age 55, paired with sodium-glucose cotransporter 2 (SGLT2) inhibitor treatment, would yield the greatest reductions in kidney failure and the largest life expectancy gains for Black adults.

The latest study evaluated this disparity from a different angle, comparing 4 different eGFR equations1:

1. Creatinine-based equation with race (eGFRcr-ASR)
2. Creatinine-based equation without race (eGFRcr-AS)
3. Cystatin C-based equation (eGFRcys-AS)
4. Combined creatinine and cystatin C equation (eGFRcr-cys-AS)

While all 4 equations found that lower eGFR was associated with a higher risk of KFRT and death, they differed in how much risk they assigned to Black patients relative to non-Black patients.

Removing race from the creatinine-based equation (eGFRcr-AS) substantially reduced the observed disparities in kidney failure risk between Black and non-Black individuals. At a clinically relevant eGFR threshold of 60 mL/min/1.73 m², the hazard ratio for progression to kidney failure was 1.3 (95% CI, 0.8–2.1) for Black vs non-Black participants using the race-free equation.

In contrast, when using the traditional race-adjusted creatinine-based equation (eGFRcr-ASR), the HR was 2.8 (95% CI, 1.6–4.9), indicating a higher risk for Black patients. Similarly, the 5-year absolute risk difference dropped from 1.4% using the race-adjusted equation to 0.37% (95% CI, −0.32% to 1.05%) without race.

These findings suggest that removing the race variable from eGFR calculations may help reduce racial disparities in predicting kidney failure without compromising risk prediction accuracy. Using eGFRcr-AS could make Black patients appear at lower risk than they actually are, potentially delaying referrals to nephrology care or eligibility for transplantation.

Over a mean follow-up of 13 years, 8% of Black participants experienced KFRT compared with 4% of non-Black participants. Mortality rates were also high, with 34% of Black and 39% of non-Black participants dying during follow-up. Yet, for all-cause and cardiovascular mortality, racial differences were again diminished or absent when using the race-free creatinine equation.

The study authors emphasize that although the combined creatinine–cystatin C equation (eGFRcr-cys-AS) provided the most accurate prediction of kidney failure, it continued to reflect significant racial disparities in risk, similar to older equations that included race. C-statistics for predicting outcomes like KFRT and mortality were significantly higher when cystatin C was included, regardless of race.

The study had several limitations, including a lack of data on social determinants of health, which limited the ability to adjust for all causes of racial differences. Variability in measurement methods across cohorts and the small number of participants from racial groups other than Black and White limited generalizability. Other important outcomes, like cardiovascular events, weren’t assessed, and physician decisions on kidney failure treatment may have been influenced by lab values not standardized across all settings.

While the shift away from using race in clinical algorithms is motivated by the need to avoid race as a biological proxy, removing race without incorporating more precise biomarkers may result in unintended harms, especially for Black patients who already face disproportionate burdens of CKD and limited access to specialty care.

"These findings support the NKF-ASN [National Kidney Foundation–American Society of Nephrology Task Force] recommendations to increase cystatin C testing, because it is less affected by muscle mass and race group than serum creatinine," the authors wrote. "This recommendation is further supported by its recommendation for confirmation of CKD in the KDIGO 2012 guidelines. Cystatin C has been standardized since 2010, improves risk prediction compared with equations that include creatinine alone, and is now integrated into early CKD detection guidelines and CKD curricula."

References

1. Gutiérrez OM, Sang Y, Grams ME, et al. Association of estimated GFR calculated using race-free equations with kidney failure and mortality by Black vs non-Black race. JAMA. 2022;327(23):2306–2316. doi:10.1001/jama.2022.8801

2. Grossi G. Cost-effectiveness analysis: CKD screening, SGLT2 inhibitors can reduce kidney failure risk, racial disparities. AJMC®. April 18, 2025. Accessed June 10, 2025. https://www.ajmc.com/view/cost-effectiveness-analysis-ckd-screening-sglt2-inhibitors-can-reduce-kidney-failure-risk-racial-disparities