Background

In December 2021, the National Kidney Foundation and the American Society of Nephrology (NKF-ASN) officially recommended excluding race from creatinine-based estimated glomerular filtration rate (eGFR) calculations (ie, Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] and Modification of Diet in Renal Disease [MDRD]).¹ As an example, the most commonly used eGFR equation over the past decade—the 2009 CKD-EPI equation—included a coefficient of 1.16 for Black patients.² Therefore, exclusion of the race coefficient formulaically results in 16% lower eGFR, with studies demonstrating median eGFR decreases of 10-14 mL/min/1.73 m².^3-5

The NKF-ASN’s decision to no longer include race in eGFR is part of a larger movement away from race-based medicine, which can feature socially constructed racial stereotypes that have contributed to the significant health disparities experienced by Black patients in the United States. Similar disparities exist for Black patients with renal function, as they experience higher rates of chronic kidney disease morbidity and mortality, 3-4× higher risk of developing kidney failure, and fewer treatments.⁶ A formal risk-benefit analysis conducted by NKF-ASN ultimately concluded it would be better to remove race from these equations, with many positive aspects such as earlier CKD diagnosis (eGFR <60 mL/min/1.73 m²); increased nephrology referral (eGFR <30 mL/min/1.73 m²), medical nutrition therapy (eGFR 13-50 mL/min/1.73 m²), and kidney disease education (eGFR 15-29 mL/min/1.73 m²); and earlier kidney transplantation eligibility (eGFR <20 mL/min/1.73 m²).⁴

As race-free eGFR becomes widely implemented in institutional laboratories and reported in electronic health records, our AUA2023 Best Poster⁷ for the “Diversity, Equity & Inclusion: Health Equity & Outcomes I” session aimed to present the effects of this change and potential urological implications that urologists should be aware of.

Study Design, Results, and Major Implications

To assess the impact of race-free eGFR in a urological cohort, we analyzed patients in our institutional renal cell carcinoma database that self-identified as Black and calculated their pre-nephrectomy eGFR with and without race. Four hundred fifty-nine Black patients with a median age of 60 were included. Use of race-free equations resulted in median eGFR values being 10 mL/min/1.73 m² and 13 mL/min/1.73 m² lower for the CKD-EPI and MDRD equations, respectively. To determine the potential clinical impact of this change, we then considered patient distribution under clinically relevant eGFR cutoff values of 60, 45, and 30 mL/min/1.73 m². As summarized in the Figure, removing the race coefficient from CKD-EPI resulted in an additional 13.3% (P < .0001), 6.6% (P = .005), and 2.2% of patients under the 60, 45, and 30 mL/min/1.73 m² cutoffs, respectively. A consistent but more extreme pattern was observed with the MDRD equation, with an additional 22.4% (P < .0001), 12.0% (P < .0001), and 3.3% (P = .0265) of patients under the 60, 45, and 30 mL/min/1.73 m² cutoffs, respectively.

Figure. Percentage of additional patients under common estimated (e) glomerular filtration rate (GFR)/chronic kidney disease (CKD) staging cutoff points (n=459). We simulated the number of patients who would be under important clinical eGFR cutoffs with the CKD-Epidemiology (EPI) WithRace and CKD-EPIWithoutRace equations (A) and the Modification of Diet in Renal Disease (MDRD) WithRace and MDRDWithoutRace equations (B).

There are many urological implications of this shift in patients under these common clinical eGFR cutoffs, which was covered in detail in our article published in the April 2023 AUANews Diversity Issue.⁸ Notably, Black patients may face increased exclusion from oncology-based clinical trials due to renal function exclusion criteria³; be excluded from receiving medications (ie, cisplatin [<60 mL/min/1.73 m²]) or be subject to reduced chemotherapy dosing (ie, etoposide/bleomycin [<50 mL/min/1.73 m²])⁵; and have their surgical decision-making altered based on inadequate renal function (ie partial nephrectomy over radical nephrectomy [<60 mL/min/1.73 m²] or neobladder creation [<30 mL/min/1.73 m²]).

Future Directions and Conclusions

In the presentation of these findings, important questions have been raised. A major interest is whether this fluctuation of Black patients under common eGFR cutoffs protects Black individuals from adverse events. For example, does excluding more Black individuals from clinical trials—which is certainly undesirable given the already significant underrepresentation of Black individuals in urological and nonurological trials⁹—ultimately protect them from experiencing kidney-related adverse events? Similarly, does reduced dosing or exclusion of chemotherapeutics based on lower eGFR values from race-free equations prevent nephrotoxic events? Finally, the validity and reliability of creatinine-based equations has been questioned, especially given their significant fluctuation based on a patient’s muscle status and weight-bearing ability.¹⁰ A movement towards alternative biomarkers for renal function estimation, such as with cystatin-C-based equations, may prove to be a more accurate and equitable method for calculating eGFR that avoids the inclusion of race altogether.

In conclusion, the decision to move away from race-based medicine is laudable. As stated, these movements—such as race-free renal function estimation—have many benefits such as earlier access to nephrology care, sooner renal transplantation, and increased utilization of partial nephrectomy. However, there may be some unintended consequences in the delivery of urological care that should be considered, as illustrated in our AUA2023 abstract. It is important for all practicing urologists to become aware of their institutional reporting standards and how these changes affect our patients so we can provide optimal care for them.