eGFR Slope Tracks Kidney Disease in Cardiovascular Trials

Tracking changes in average estimated glomerular filtration rate (eGFR) over time — the eGFR slope — among people enrolled in cardiovascular outcome trials of new treatments is a potentially helpful way to gauge progression of chronic kidney disease (CKD), five authors propose in a new review in JAMA Cardiology.

Calculation of eGFR slope "may serve as a valuable marker to determine progression of CKD in cardiovascular trials," writes Muhammad S. Khan, MD, and colleagues in a review published online January 5 in JAMA Cardiology.

The authors also caution, however, that "further work is required" to make eGFR slope an established trial outcome, including standardizing the collection of these data, determining an appropriate duration of follow-up and timing of renal function assessment, and identifying optimal ways to calculate eGFR slope.

A problem with traditional measures of progressive CKD in cardiovascular outcome trials, such as the incidence of end-stage kidney disease or a 40% or greater worsening of eGFR, is that often the patient dies before they reach this endpoint.

"The competing risk of death may considerably attenuate the observance of hard kidney outcomes," write Khan, a cardiologist at Duke University in Durham, North Carolina, and colleagues.

On the other hand, the "strength of association between eGFR slope and outcomes confers the possibility that eGFR slope may provide insight into CKD progression."

A limited number of studies have shown "an association between eGFR slope and subsequent risk of cardiovascular disease, kidney disease progression to end-stage, and mortality," they note.

GFR Slope Is a "Strong Surrogate End Point"

This is not the first report suggesting a role for eGFR slope as a surrogate marker for CKD progression. Results from a meta-analysis of 47 randomized, controlled trials published in 2019 suggested that "total and chronic GFR slope are strong surrogate end points and may be used as endpoints for randomized, controlled trials of kidney disease progression in certain circumstances in both early and late CKD."

But variations across multiple trials in specific approaches to calculating eGFR slope "make it difficult to compare data across trials and warrant a standardized framework," the authors say in the new review.

In a report published December 30, 2021 in the European Heart Journal, several of the same coauthors write that "significant heterogeneity in reporting of kidney function and kidney outcomes in large type 2 diabetes, kidney, and heart failure trials underscores the need for future stakeholders to draft a consensus solution." Their review of 33 recent trials of these types showed that fewer than half the reports included information on eGFR slope.

The review did not include a statement about funding sources. Khan has reported no relevant financial relationships. Several authors have reported receiving consulting or personal fees from various drug companies.

JAMA Cardiol. January 5, 2022. Full text

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

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