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New eGFR Equation ‘Less Biased’ by Age, Kidney Function; Some Disagree

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A new equation for estimating glomerular filtration rate (eGFR), a measure of kidney function, shows improved accuracy and precision compared with commonly used equations.

The European Kidney Function Consortium (EKFC) equation surpasses existing equations by “resulting in generally lower bias across the spectrum of age and kidney function,” its developers write in an article published online November 9 in Annals of Internal Medicine.

“The new EKFC equation may have helpful properties and perform better in estimating GFR compared with the current KDIGO [Kidney Disease: Improving Global Outcomes] recommended equations,” they add.

The primary KDIGO recommended equation in its most recent guideline was the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, designed for adults, and a companion equation, the CKiD, covers children and adolescents.

“Key in our [new] equation is the adjustment for differences in serum creatinine generation between children and adults, or between men and women,” lead author Hans Pottel, PhD, KU Leuven, Belgium, told Medscape Medical News.

In an accompanying editorial, Andrew M. Levey, MD, and associates write: “We agree that a single eGFR equation that can be used in children and adults and performs well in the transition from adolescence to young adulthood is a worthy goal.”

“But the claim of equivalent or superior performance compared with the CKD-EPI equation is not conclusive,” claim Levey, who led the research team that developed the CKD-EPI equation, and coauthors.

Levey is professor of medicine at Tufts University School of Medicine in Boston, Massachusetts.

Whats New Is Q

Pottel and codevelopers devised what they call Q values: age- and sex-dependent median creatinine levels in normal individuals.

Q values act to “normalize or rescale creatinine before entering it into the equation, because we know that creatinine generation is different” based on factors that include age, sex, and muscle mass.

The EKFC equation extends the CKD-EPI equation and first eGFR equation by using Q values and applying across age ranges, like the full-age spectrum (FAS) equation, first reported in 2016 by a team led by Pottel.

“Although the FAS equation was designed to overcome the challenge in measuring GFR in patients transitioning from adolescence to adult nephrology care, it also underestimates GFR at low serum creatinine values and in patients with chronic kidney disease,” write Pottel and coauthors.

Hence, their intent to tweak the FAS equation to overcome this limitation and create the EKFC equation.

“The new equation combines the strengths of the CKD-EPI and FAS equations,” they write.

However, “We acknowledge that lack of precision is still a major problem with all eGFR equations,” including the new EKFC, they add.

Editorialists Dispute Better Performance of EKFC Over CKD-EPI

In their editorial, Levey and coauthors note the EKFC equations and other adapted equations in development “represent a conceptual advance over the FAS equations,” but they dispute the claims of better performance compared with the CKD-EPI.

“We compared the performance of the EKFC and CKD-EPI equations in a different, large external validation population of Black and non-Black adults,” the external population used to validate the CKD-EPI equation, the editorialists report.

The upshot was “our results did not confirm the author’s conclusions” about the EKFC equation.

In response, Pottel highlighted that the EKFC equation is currently not designed for use in Black patients.

“With its derivation and validation now reported in the new article, the EKFC equation is fully validated and ready for routine use in Whites,” he said. “We plan to evaluate and possibly fine tune our equation for its application in other ethnicities.”

Regarding the inferior performance compared with the CKD-EPI equation in the non-Black population tested by the editorialists, Pottel cited “calibration issues for serum creatinine” that some experts have found in the datasets compiled by developers of the CKI-EPI equation that could limit the utility of these data.

Still Room for Improvement; App Hopefully Coming Next Year

Pottel and coauthors developed and validated the EKFC equation with data from 19,629 patients drawn from 13 cohorts. This included 11,251 patients from seven cohorts for development and internal validation, and 8378 from six cohorts for external validation. The EKFC effort received endorsement from the European Renal Association-European Dialysis and Transplant Association.

However, “We acknowledge that there is still room for improvement,” Pottel said.

Although the new report presents the EKFC equations (actually two slightly different equations depending on whether a patient’s serum creatinine is higher or lower than the relevant Q value), most potential users will likely find the equations easier to work with once they’re in an app form that allows someone to simply plug in age, sex, and serum creatinine level. That app currently doesn’t exist but is coming soon, promised Pottel.

“I hope to have an electronic tool by the beginning of 2021,” he said. “I have to find a programmer who can do this for me.”

The EKFC project has received no commercial funding. Pottel reported no relevant financial relationships. Levey has reported receiving research funding from AstraZeneca.

Ann Intern Med. Published online November 9, 2020. Abstract

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