Introduction

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 [CKD] Epidemiology Collaboration [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 min².^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 due to race being a social construct and significant health disparities experienced by Black patients in the United States.⁶ Similar disparities exist for Black patients and renal function, as they experience higher rates of chronic kidney disease morbidity and mortality, 3-4 times higher risk of developing kidney failure, and fewer treatments.⁷ 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).^4,8

Race-free eGFR: Considerations in Urology

The removal of race from eGFR and the resulting lower eGFR values have clinical and research implications that urologists should be aware of. Here, we first consider clinical trial and chemotherapy considerations. Then, we discuss the effect of race-free eGFR on nephrectomy decision-making and follow-up.

Clinical Trials

Black patients are underrepresented in cancer clinical trials. Despite being 13% of the population, only 5% of oncology clinical trial participants identify as Black, a disparity that holds true for urologic oncology clinical trials.^9,10 Notably, more than 80% of oncology randomized controlled clinical trials may have some form of renal function exclusion criteria, with 39% having eGFR cutoffs ≥ 45 mL/min.¹¹ Our group simulated the effects of race-free CKD-EPI and MDRD eGFR equations and the fluctuation of patients undergoing nephrectomy at common clinical trial eGFR cutoff points. Results demonstrated 13% and 22%, 7% and 12%, and 2% and 3% more patients may fall under 60, 45, and 30 mL/min/1.73 m², respectively, using the CKD-EPI and MDRD equations (see Figure).³ This increase in patients under common eGFR cutoffs may potentially lead to further exclusion and underrepresentation of Black patients in clinical trials.

Figure. Percentage of additional patients excluded from clinical trials at common glomerular filtration rate (GFR)/chronic kidney disease (CKD) staging cutoff points for all patients of any T-stage (n=459). We simulated the number of patients who would be excluded from clinical trials based on (A) the CKD–Epidemiology Collaboration (EPI)-WithRace, CKD-EPI-WithoutRace, and (B) Modification of Diet in Renal Disease (MDRD)-WithRace and MDRD-WithoutRace equations, and noted the percentage of additional patients excluded from trials when compared to their equation counterpart with the race coefficient. ns indicates not significant. Figure reprinted with permission from Schmeusser et al, Cancer. 2023;129(6):920-924.³

Chemotherapy Considerations

In addition to clinical trial eligibility, race-free eGFR may limit chemotherapeutic regimens on the basis of renal function criteria. For example, an analysis of 340 Black patients found significantly more Black patients may experience chemotherapeutic undertreatment either by ineligibility or reduction in therapeutic dosing.⁵ Simulations have found 6%-13% more Black patients may fall under an eGFR of 60 mL/min/1.73 m² with race-free CKD-EPI, effectively excluding those patients from the commonly used bladder cancer chemotherapeutic cisplatin.^3,5 Similarly, testicular cancer drugs etoposide and bleomycin require a dose reduction of ∼25% for eGFR <50, with simulations identifying 4%-6% more Black patients falling under this eGFR criterion.^3,5 Notably, it is possible that increased exclusion or reduced dosing secondary to eGFR criteria may also reduce nephrotoxic events associated with chemotherapeutics, though this has yet to be determined.⁵

Nephrectomy Decision-making

In addition to chemotherapeutics and clinical trials, lower eGFR based on the removal of race coefficients may impact surgical decision-making for patients with renal cell carcinoma. Patients with CKD IIIa (< 60 mL/min/1.73 m²) or an estimated baseline glomerular filtration rate of < 45 mL/min/1.73 m² post-nephrectomy are recommended to avoid radical nephrectomy (RN) in favor of nephron-sparing approaches.¹² It has been demonstrated that Black patients disproportionately undergo more RN compared to partial nephrectomy (PN). This disparity may be partially attributed to the higher estimated eGFR resulting from race-based eGFR equations.^13,14 PN is often favored given its preservation of renal mass and function; however, instances may arise where RN may present itself as the most appropriate and safer operation from an anatomical or oncologic perspective, such as endophytic masses or central masses.^12,15 Additionally, it is critical to recognize which eGFR equations were used pre-nephrectomy and post-nephrectomy to better understand postoperative renal function given that removal of the race coefficient results in eGFR lowering by 10+ points for Black patients regardless of treatment-related changes.

Furthermore, multiple post-nephrectomy eGFR (fGFR) prediction equations have been developed to assist with nephrectomy decision-making.¹⁶ One recent fGFR equation that uses only 5 routine preoperative variables—preoperative eGFR, PN or RN, age, tumor size, and diabetes status—has exhibited >80% accuracy.¹⁷ Our group examined race-free preoperative eGFR on the predictive ability of this fGFR equation to determine its effect on accuracy in >1,400 patients, with ∼330 being Black. Results demonstrated that Black patients experience comparable accuracy using the 2009 race-based CKD-EPI compared to non-Black patients (78.5% vs 82.1%, P = .146). Using the 2021 race-free CKD-EPI equation, accuracy was statistically lower for Black patients vs non-Black patients at 76% vs 83% (P = .003). While lower, this difference in accuracy may not be clinically significant but is an aspect to consider when using fGFR.

Conclusions

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 PN. However, there may be some ulterior consequences in the delivery of urologic care that should be considered, as illustrated in this report. For example, a patient’s eGFR may appear to be worsening simply due to altered reported eGFR. Alternatively, a patient treated with chemotherapeutics or nephrectomy may appear to have pre- to post-treatment eGFR changes more drastic than normal given the change in the eGFR equation used in the electronic record. Furthermore, estimates from post-nephrectomy eGFR equations may vary depending on inserted preoperative eGFR.

While alternative and more equitable race-free eGFR equations are increasingly pursued, such as cystatin-C-based equations,^1,18 these are yet to be the most often reported values. 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.