Acute eGFR Changes and Their Mediation of Albuminuria Reduction with Empagliflozin and Finerenone.
Rajiv Agarwal, Ricardo Correa-Rotter, Sankar D Navaneethan et al.
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In 30 seconds
This mostly prespecified analysis of the randomized CONFIDENCE trial examined acute eGFR changes and albuminuria reduction in 790 people with type 2 diabetes, chronic kidney disease, and albuminuria receiving empagliflozin, finerenone, or both. At day 14, mean eGFR decline was greater with combination therapy (-6.6 ml/min per 1.73 m 2) than with finerenone (-2.1 ml/min per 1.73 m 2) or empagliflozin (-4.8 ml/min per 1.73 m 2) alone (P < 0.001). Acute decline was more pronounced with higher baseline eGFR and diuretic use; mediation analysis suggested different contributions of eGFR change to albuminuria reduction between drugs.
Key findings
- Mean acute eGFR decline was -6.6 ml/min per 1.73 m 2 with combination therapy, versus -2.1 ml/min per 1.73 m 2 with finerenone and -4.8 ml/min per 1.73 m 2 with empagliflozin (P < 0.001).
- Higher baseline eGFR and baseline diuretic use were associated with more pronounced acute eGFR decline (P < 0.001 for both).
- Acute eGFR change mediated 28% of empagliflozin's added effect on UACR reduction, compared with 5.2% of finerenone's added effect.
- Acute eGFR changes were reported as reversible, and AKI was uncommon across treatment groups.
Why it matters
An early eGFR decline can accompany these therapies, particularly when used together, and may prompt treatment interruption. The findings help characterize which participants had larger acute changes and suggest that the relationship between eGFR change and albuminuria reduction differs by drug. AKI was uncommon in this analysis, although the results do not establish how individual treatment decisions should be made.
What to keep in mind
The mediation analysis was exploratory, and the reported outcomes focus on acute eGFR change and UACR rather than long-term kidney outcomes.