Kidney Failure Risk Equation Works Without Race Adjustment

Mitchel L. Zoler, PhD

January 10, 2022

The recently introduced and endorsed equation for estimated glomerular filtration rate (eGFR) that foregoes adjustment for self-identified Black individuals worked as well as the race-adjusted version of the same equation when plugged into the four-variable Kidney Failure Risk Equation (KFRE) in a retrospective study of observational data from more than 3800 American adults.

The results also served to further validate the superior prognostic ability of the four-variable KFRE compared with eGFR alone.

This KFRE, first introduced a decade ago and more extensively validated in a 2016 report, combines a person's eGFR with adjustments for age, sex, and urinary albumin-to-creatinine ratio to produce a more accurate estimate for the risk of developing end-stage kidney disease (ESKD) in a person with chronic kidney disease (CKD).

In the new study, a KFRE score greater than 20% "showed similar specificity but higher sensitivity compared with eGFR alone of less than 20 mL/min/1.73m2. A KFRE score is easy to implement in routine clinical settings, and it does not consider race. Therefore, the KFRE should be widely used in clinical practice. Our findings support wider adoption," said senior study author Jiang He, MD, PhD.

The new report was published online January 10 in Annals of Internal Medicine by Joshua D. Bundy, PhD, of Tulane University, New Orleans, Louisiana, and colleagues.

KFRE Better Than eGFR Alone

"The KFRE is not commonly used in current US nephrology practice, but our results indicate that the KFRE score predicts patients' 2-year risk for ESKD better than eGFR alone regardless of race adjustment," He said in an interview.

"Future guidelines should recommend using the KFRE score as the primary indicator for determining transplant eligibility and referral for dialysis, and insurers and health agencies should develop policy on using the KFRE score as the primary indictor for kidney replacement therapy," added He, professor and chair of epidemiology at the School of Public Health and Tropical Medicine of Tulane University.

Nephrologist Paul M. Palevsky, MD, agreed that the new report's findings further buttress the case for favoring a KFRE score to assess patients rather than eGFR alone, but he disagrees that until now the KFRE has been ignored in US practice.

"I use the KFRE, and we train nephrologists to consider both eGFR and urinary albumin-to-creatinine ratio" when assessing the risk of a patient with CKD to progress to ESKD, said Palevsky, chief of the renal section for the VA Pittsburgh Healthcare System, Pennsylvania.

However, he acknowledged that how widespread KFRE use is in the United States is not known.

Palevsky, who is also president of the National Kidney Foundation, worked with the leadership of the American Society of Nephrology to form a task force that in September 2021 recommended adopting a new eGFR equation that dropped race-based adjustment. Palevsky and others from the NKF and ASN have worked to promote use of the new eGFR equation in the United States since its introduction in a report first published online in September 2021 and endorsed by the task force.

"Relatively Rapid" Uptake of New eGFR Equation

By early 2022, uptake of the new eGFR equation "has been relatively rapid, although not as fast as I'd like," Palevsky said in an interview. For example, several VA systems have already implemented the race-neutral equation, including Palevsky's VA system in Pittsburgh, as have many other US health systems.

But complete adoption by some of the largest US lab-testing companies is still in process at the start of 2022, he said.

The study by Bundy and colleagues used data collected from 3873 Americans aged 21- to 74-years-old with mild-to-moderate CKD who were prospectively enrolled in the Chronic Renal Insufficiency Cohort Study in 2003-2008 and underwent follow-up for an average of more than 9 years. Participants were an average of 58 years old, 55% were men, and 42% self-identified as Black.

From the follow-up data, researchers determined there were 13,902 distinct 2-year follow-up periods, during which participants developed 856 episodes of ESKD.

They compared the ability of the four-variable KFRE to predict the 2-year risk for these events when using any of five different ways of calculating eGFR, including the new formula introduced in late 2021. The five different eGFR formulas relied on:

  • creatinine, age, and sex;

  • cystatin C, age, and sex;

  • creatinine, age, sex, and race;

  • creatinine, cystatin C, age, and sex;

  • creatinine, cystatin C, age, sex, and race.

The results showed that across all five methods for calculating eGFR the KFRE score was superior for predicting 2-year risk for ESKD compared with eGFR alone among both Blacks and non-Blacks.

The findings also showed that among both Blacks and non-Blacks the discrimination of the KFRE score was similar regardless of which of these five different approaches was used to calculate eGFR.

KFRE Beats eGFR on Specificity

A consistent finding was that risk predictions by the KFRE edged out predictions based on eGFR alone for sensitivity, an advantage for the KFRE that the authors call "substantially higher."

Among Blacks, an eGFR of 20 mL/min/1.73m2 or less had a specificity of 95%-96% and sensitivity of 49%-66%. Also among Blacks, a KFRE score of at least 20% predicted ESKD with a specificity of 94%-95% and a sensitivity of 69%-78%.

Among non-Blacks, the same eGFR cutoff predicted ESKD with a specificity of 96%-98% and sensitivity of 42%-51%. In contrast, a KFRE score of 20% or greater predicted ESKD with a specificity of 95%-97% and a sensitivity of 68%-74%.

The superiority of the KFRE over eGFR alone for predicting ESKD was especially notable for people with levels at or near cutoff values.

A risk-based assessment of patients by the KFRE "may not only improve prediction of ESKD among patients with CKD, but simultaneously allows clinicians and health systems to not rely on self-reported race, which is a controversial and ill-defined social construct," the authors add.

An accompanying editorial highlights that elimination of race adjustment when calculating eGFR does not address more fundamental disparities in the healthcare received by US Blacks.

Need to Address Kidney-Health Inequities

"Enduring kidney-health inequities in people of Black race have been with us for decades, and the effortful tokenism of revisions to eGFR estimating equations will not have any materially significant effect on kidney-health inequities experienced by Black patients with CKD," writes Akinlolu Ojo, MD, PhD, professor of public health and executive dean of the University of Kansas School of Medicine in Kansas City, in the editorial.

The focus instead needs to be on "improving our healthcare and public health systems, not on fine-tuning the estimating equations for GFR, nor on validating KFRE scoring with or without refitted [eGFR] equations," says Ojo.

The study received no commercial funding. The authors, Ojo, and Palevsky have reported no relevant financial relationships.

Ann Int Med. Published online January 10, 2022. Abstract, Editorial

Mitchel L. Zoler is a reporter for Medscape and MDedge based in the Philadelphia area. @mitchelzoler

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