Race-Free Kidney Equation Changes Status of Millions in US

The race-free, creatinine-based equation for calculating estimated glomerular filtration rate (eGFR), introduced in 2021 and gaining traction as the default tool for assessing kidney function in routine US practice, is expected to identify about 434,000 new cases of chronic kidney disease (CKD) among Black adults.

At the same time, use of the new equation would undo a CKD diagnosis for about 5.5 million non-Black adult Americans, based on novel data from more than 44,000 Americans collected from nine sequential, 2-year iterations of the National Health and Nutritional Examination Survey (NHANES) run in 2001-2018 and recently published in the Journal of the American Society of Nephrology.

These fresh estimates — the most specific numerical projections calculated to date from a broadly representative sample of Americans — project changes in recommended care, including CKD diagnoses, disease staging, medication dosing, insurance coverage, and kidney transplant eligibility.

The findings “extend the work of prior studies” of the race-free equation by predicting “downstream implications,” explained James A. Diao, lead author and a researcher at Harvard Medical School in Boston, Massachusetts.

The new data “are an important and meaningful addition to research into kidney-function estimating equations,” commented Carl P. Walther, MD, a nephrologist at Baylor College of Medicine in Houston, Texas, who played no role in the new report but conducted his own study on the projected impact of the new equation that had generally similar findings using a smaller, NHANES-derived US database.

The latest report from Diao and colleagues “confirms prior results and extends them to a wide range of medications and medication-related questions,” Walther said in an interview.

Changes in Medication Predicted, Particularly ACE Inhibitors and ARBs

The new data show that adoption of the race-free, creatinine-based 2021 eGFR equation developed by the CKD-Epidemiology Collaboration (CKD-EPI) would lead to “substantial changes to medication selection and dosing,” with more than 200,000 Black American adults reclassified to a lower eGFR level that should trigger dose reduction or treatment cessation of a variety of medications, including angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), collectively known as renin-angiotensin system inhibitors (RASis).

In contrast, use of the race-free equation would result — if broadly adopted in US practice — in roughly 1.5 million non-Black adults no longer needing a dose reduction or a halt to treatment of the same medications, says the report.

“The investigation of RASi is particularly interesting, given that these classes of medications are central to preserving kidney function in many people with kidney disease,” Walther noted.

Although the ACE inhibitors and ARBs “have been shown safe and effective even in people with advanced CKD, it seems likely that altered eGFR numbers due to changing the estimating equation may influence RASi choice and dosing.”

And if changing the equation used to calculate eGFR results in “avoidance or reduced doses of RASi therapy, it can potentially cause harm,” Walther cautioned.

Thus, he surmised: “It is not clear what practice changes would best deal with the change in eGFR calculation. The challenge for clinical practice is to individualize therapy and not be dissuaded from effective therapies because of low eGFR.”

Comparisons With Older eGFR Equations

For their analysis, Diao and colleagues compared eGFR results between the 2021 race-free, creatinine-based CKD-EPI equation and two prior creatinine-based equations. Both comparator equations included a race-based modifier that increased the calculated eGFR of people who self-identified as Black: the 2006 MDRD equation, by 21% in people who identify as Black, and the 2009 CKD-EPI equation, which increases eGFR by about 16% for adults who self-identify as Black.

They used data from 44,360 NHANES participants during 2001-2018, and extrapolated findings from this representative sample to estimate how US numbers would shift on a national scale relative to the MDRD equation, which until recently was the most widely used way to calculate eGFR in US practice, and the 2009 CKD-EPI equation, a direct precursor to the creatinine-based 2021 CKD-EPI equation.

Other large swings in diagnosis that the new study documented in its projections included a reclassification of about 584,000 Black American adults to a more advanced stage of CKD by using the new race-free equation, while at the same time reclassifying about 4.6 million non-Black American adults to a less advanced CKD stage.

“We hope our [findings] will help inform adoption of the new [race-free] eGFR equation,” Diao said in an interview.

Race-Free eGFR Equation Catches On, So Too May Cystatin C Testing

Early indications are that adoption of the new race-free eGFR equation is proceeding relatively briskly. A report of survey results from nearly 4300 US laboratories conducted in March 2022 — a scant 6 months after introduction of the 2021 equation — documented a 30% uptake rate with an equal rate planning use by the end of 2022.

The largest US commercial labs have also adopted the new equation, and another big boost to uptake came when the board of directors of the Organ Procurement and Transplantation Network unanimously passed a measure effective in July 2022 requiring US transplant hospitals to use a race-neutral calculation when estimating kidney function.

Walther also noted that the recent shift in the way US clinicians calculate eGFR bolsters the case for also using other measures of kidney function that are more reliable, such as cystatin C.

Diao agreed. “We’ve seen increased interest in confirmatory testing [of eGFR] using cystatin C” as an adjunct to creatinine. While routine cystatin C testing has been poorly used until now largely due to its higher cost and reduced availability compared with creatinine measurement, cystatin C use may start picking up now that the 2021 CKD-EPI equation has upended eGFR calculation.

The study by Diao and colleagues did not receive commercial funding. Diao and Walther have reported no relevant financial relationships. Disclosures for other study authors are listed with the article.

J Am Soc Nephrol. 2023;34:309-321. Abstract

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

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