Including race coefficient in GFR estimate associated with greater biases, delayed transplant eligibility

Estimated glomerular filtration rates (eGFR) in patients with chronic kidney disease (CKD) calculated with equations that include the race coefficient may be associated with a greater bias in GFR estimation, as well as with delayed achievement of a clinical threshold for kidney transplant referral and eligibility.

Researchers advised nephrologists and health care professionals involved in kidney transplant programs to be cautious when using estimating equations to determine Black patients’ eligibility for kidney transplant — they published the results of their study in JAMA Network Open.

“Racial disparities in kidney transplantation are well recognized and persistent despite changes in organ allocation in the U.S. Black patients are less likely to be referred for transplant, less likely to be wait-listed, and less likely to receive a kidney transplant despite transplant being associated with improved survival and quality of life compared with dialysis. Patients are considered eligible for kidney transplant evaluation after their glomerular filtration rate (GFR) decreases to less than 20 mL/min/1.73 m2. In most cases, the GFR is estimated from equations to determine this transplant eligibility. Recently, the estimating equations for GFR have been debated since the most commonly used estimation applies a race coefficient that increases the estimated GFR (eGFR) for patients identified as Black,” wrote Leila R. Zelnick, PhD, of the Kidney Research Institute at the University of Washington, Seattle, and colleagues.

But unraveling the arguments for across-the-board inclusion of a race coefficient is complicated, they added.

“Race is a complex social construct and is distinct from biological variables, such as ancestry. Moreover, the coefficient was applied to statistically adjust for non-GFR factors associated with serum creatinine level, including differences in muscle mass in Black persons, which may not apply to all Black persons, particularly in the context of CKD and frailty. Furthermore, definitions of race may be subject to significant bias because race may be self-reported or assigned by a clinician or observer. It is possible that by increasing the estimate of GFR, inclusion of the race coefficient in these equations may contribute to health disparities, including eligibility for kidney transplant, which uses a strict GFR cutoff,” they wrote.

In this prospective study, therefore, Zelnick and colleagues sought to compare eGFR with measured GFR, as well as search for associations between eGFR calculated both with and without race and time to transplant eligibility coefficients.

The included 1,658 self-identified Black participants (mean age: 58 years; 51% female; mean eGFR: 44 mL/min/1.73 m2) with CKD from the Chronic Renal Insufficiency Cohort (CRIC). Participants underwent annual GFR estimations using the following estimating equations:

  • The creatinine-based CKD-EPI equation, including the race coefficient (CKD-EPIRC).
  • The creatinine-based CKD-EPI equation not including the race coefficient (CKD-EPIWRC).
  • The cystatin C-based CKD-EPI equation, not including the race coefficient (CKD-EPICYS).

Among the Black participants in the study, Zelnick and colleagues found that eGFR CKD-EPIWRC (r=0.75) had the strongest correlation with iothalamate GFR (iGFR), compared with eGFR CKD-EPIRC (r=0.61) or eGFRCYS (r=0.03).

In addition, they found that the CKD-EPIRC eGFR overestimated iGFR by a mean of 3.1 mL/min/1.73 m2 (95% CI: 2.2-3.9 mL/min/1.73 m2P< 0.001), while the mean difference between CKD-EPIWRC eGFR and iGFR was smaller (−1.7 mL/min/1.73 m22).

In patients with an iGFR of 20-25 mL/min/1.73 m2, the mean difference between eGFR with the race coefficient and iGFR was 5.1 mL/min/1.73 m2 (95% CI: 3.3-6.9 mL/min/1.73 m2), compared with 1.3 mL/min/1.73 m2 (95% CI: −0.3 to 2.9 mL/min/1.73 m2) in estimations calculated without the race coefficient.

During the median 4-year follow-up, calculations of eGFR done without and with the race coefficient were associated with a 35% (95% CI: 29%-41%) higher risk of achieving an eGFR less than 20 mL/min/1.73 m2 and a shorter median time to this end point (1.9 years).

Among the 1,338 patients with an eGFR of at least 30 mL/min/1.73 m2 at baseline, 746 demonstrated an eGFR of less than this when the race coefficient was not used. When the race coefficient was used to calculate eGFR, 579 patients achieved this outcome, and 617 did so when CKD-EPICYS was used for calculation.

In this subgroup, after a median follow-up of 2.2 years, CKD-EPIWRC was associated with a 52% (95% CI: 45%-59%) higher risk of an eGFR of less than 30 mL/min/1.73 m2 compared with calculations using CKD-EPIRC, with a difference in median time to event of 3.6 years. Further, this association was strongest in patients who had lower baseline eGFRs.

Calculations made using CKD-EPICYS were associated with an 11% (95% CI: 5%-18%) higher risk of an eGFR ˂30 mL/min/1.73 m2 compared with calculations made with CKD-EPIRC.

“Kidney transplants, especially from living donors, confer superior outcomes for individuals with kidney failure. Yet Black individuals in the United States, who are 2- to 4-fold more likely to develop kidney failure than White individuals, have been less likely to receive transplants during the last 3 decades. There is an urgent need to eliminate multilevel causes of this profound inequity,” wrote L. Ebony Boulware, MD, MPH, of Duke University School of Medicine, Durham, NC, and fellow authors in an accompanying editorial.

They noted that findings that after removing the Black race coefficient, the CKD-EPI eGFR consistently underestimated kidney function by −1.7 mL/min/1.73 m2 and the CKD-EPICYS overestimated iGFR among Black patients by 5.6 mL/in/1.73 m2.

“These findings highlight potentially significant clinical imprecision conferred by use of the CKD-EPI equations to estimate directly measured kidney function in Black individuals,” wrote Boulware and colleagues.

“Precise and individualized measures of kidney function are needed to guide kidney care. While we await these measures, the study by Zelnick et al provides evidence to support universal removal of the Black race coefficient from the eGFR equation as an important action toward rectifying longstanding transplant inequities for Black individuals and to ensure we do not unintentionally perpetuate them,” they concluded.

Limitations of this analysis are the inability to infer eligibility for kidney transplant due to other comorbidities and the inability to generalize these results in patients with more frequent eGFR monitoring due to the inclusion of specific patient subgroups.

  1. Not including a race coefficient when estimating kidney function is significantly associated with a shorter time to achieving an estimated glomerular filtration rate less than 20 mL/min/1.73 m2.

  2. Biases in race-based glomerular filtration rate estimates may be associated with delays in potential kidney transplant eligibility.

E.C. Meszaros, Contributing Writer, BreakingMED™

This study was supported by the Northwest Kidney Centers and the National Human Genomes Research Institute, National Institutes of Health.

Boulware and Zelnick reported no disclosures.

Cat ID: 127

Topic ID: 81,127,632,730,127,471,925