Quantifying the renal and cardiovascular risk reduction effects of fenelidone

The nonsteroidal mineralocorticoid receptor antagonist finerenone (Finerenone) has been shown to reduce cardiovascular and renal failure outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes. Fennelidone also reduces the urinary albumin to creatinine ratio (UACR). According to the study, there are few data on whether fenelinone-induced changes in UACR mediate cardiovascular and renal failure outcomes.

The researchers conducted a post hoc analysis of pooled data from two Phase 3 double-blind trials of fenelidone to quantify the proportional reduction in renal and cardiovascular risk mediated by changes in kidney damage over 4 years, as measured by the change in log UACR between baseline and month 4. The trials were conducted at clinical sites in 48 countries and included 12,512 patients with CKD and type 2 diabetes. These trials compared the treatment effects of fenelidone and placebo.

The current analysis was conducted separately for composite renal outcomes (renal failure, sustained decline in estimated glomerular filtration rate [eGFR] ≥57% from baseline, or death from renal disease) and cardiovascular outcomes (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure). The median UACR at baseline was 514 mg/g.

In the fenelidone group,53.2% of participants (n=3338) experienced a ≥30% decrease in UACR compared with 27.0% (n=1684) of the placebo group. When analyzed as a continuous variable, reduction in UACR mediated 84% of the treatment effect on renal outcomes and 37% of the treatment effect on cardiovascular outcomes. When change in UACR was analyzed as a binary variable (whether the guideline-recommended 30% reduction threshold was met or not), the proportion of mediation was 64% for renal outcomes and 26% for cardiovascular outcomes.

In patients with chronic kidney disease and type 2 diabetes, reduction of early proteinuria accounts for a large proportion of the treatment effect against CKD progression and a moderate proportion of the effect against cardiovascular outcomes.