Impact of Finerenone-Induced Albuminuria Reduction on Chronic Kidney Disease Outcomes in Type 2 Diabetes : A Mediation Analysis.
In a pooled mediation analysis of the FIDELIO-DKD and FIGARO-DKD trials, early finerenone-induced reduction in albuminuria accounted for a large share of the kidney protection but only a modest share of the cardiovascular benefit in patients with CKD and type 2 diabetes.
Background
Finerenone, a nonsteroidal selective mineralocorticoid receptor antagonist, reduces cardiovascular and kidney failure outcomes and also lowers the urine albumin-to-creatinine ratio (UACR) in patients with chronic kidney disease (CKD) and type 2 diabetes. Whether the early change in albuminuria explains, or mediates, the drug's effect on hard clinical outcomes had not been quantified.
Study design
This post hoc mediation analysis pooled data from two phase 3, double-blind, placebo-controlled trials (NCT02540993 and NCT02545049) comprising 12,512 patients randomized 1:1 to finerenone or placebo. Investigators quantified the proportion of the kidney and cardiovascular treatment effects over approximately 4 years that was mediated by the change in log UACR between baseline and month 4. Median baseline UACR was 514 mg/g.
Key findings
A reduction of 30 percent or greater in UACR occurred in 53.2 percent of the finerenone group versus 27.0 percent of the placebo group. Analyzed as a continuous variable, the early change in UACR mediated 84 percent of the treatment effect on the composite kidney outcome and 37 percent of the effect on the cardiovascular outcome. When the change was treated as a binary 30-percent threshold, the proportions mediated were 64 percent and 26 percent, respectively.
Clinical implications
Early albuminuria reduction explains a large fraction of finerenone's kidney protection, reinforcing UACR as an actionable early treatment target and surrogate for CKD progression in diabetic kidney disease. The cardiovascular benefit, by contrast, appears to operate substantially through mechanisms beyond albuminuria lowering. The authors caution that these mediation findings are specific to finerenone and are not readily generalizable to other drug classes.
Category
Research
Source
Ann Intern Med
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