Use of finenerone to reduce albuminuria improves kidney, cardiovascular outcomes
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Key takeaways:
- Reduction of albuminuria benefited patients with CKD, type 2 diabetes.
- Patients who had 30% or greater reduction in urine albumin-to-creatinine ratio had fewer kidney and cardiovascular events.
The use of finenerone to reduce albuminuria in patients with chronic kidney disease and type 2 diabetes provided kidney and cardiovascular benefits when the urine albumin-to-creatine ratio was reduced by 30% or more, a study shows.
“In patients with chronic kidney disease (CKD) and type 2 diabetes (T2D), finerenone, a nonsteroidal mineralocorticoid receptor antagonist, reduces cardiovascular and kidney failure outcomes. Finerenone also lowers the urine albumin-to-creatinine ratio (UACR). Whether finerenone-induced change in UACR mediates cardiovascular and kidney failure outcomes is unknown,” Rajiv Agarwal, MD, MS, a professor of medicine at Indiana University School of Medicine at Indianapolis, and colleagues wrote in describing the objectives of the study.
Kidney injury
The researchers analyzed pooled data from the phase 3 FIDELIO-DKD and FIGARO-DKD trials.
This study included 12,512 patients with CKD and T2D given either finerenone (Kerendia, Bayer) or placebo. Risk reduction was measured by a change in kidney injury indicated by the change in UACR from baseline to the fourth month of treatment.
Several clinical sites in 48 countries were chosen for the study.
At baseline, the median UACR was 514 mg/g in both patient groups. “A 30% or greater reduction in UACR was seen in 3,338 (53.2%) patients in the finerenone group and 1,684 (27%) patients in the placebo group. Reduction in UACR (analyzed as a continuous variable) mediated 84% and 37% of the treatment effect on the kidney and cardiovascular outcomes, respectively,” the researchers wrote. “When change in UACR was analyzed as a binary variable (that is, whether the guideline-recommended 30% reduction threshold was met), the proportions mediated for each outcome were 64% and 26%, respectively.”
Cardiovascular outcomes
Patients who showed improvement in kidney outcomes had a UACR of 300 mg/g or greater, the researchers said. While the benefits of a reduced UACR were less for cardiovascular outcomes among patients taking placebo — “there was little discernible difference in composite cardiovascular outcomes whether patients had 30% or greater reduction or less than 30% reduction in UACR among those who received placebo,” the researchers wrote — patients who received finerenone and achieved 30% or greater reduction in UACR “had fewer composite cardiovascular outcome events than those who did not” receive the drug, the researchers wrote.
“Our findings indicate that an early finerenone-induced reduction in UACR may mediate a substantial proportion (84%) of the effect on long-term kidney outcomes, that this benefit was more pronounced in patients with a 30% or greater reduction in UACR after 4 months of treatment, and that this effect was largely driven by patients with UACR of 300 mg/g or greater,” the researchers concluded.
“ ... [I]n addition to showing that change in kidney injury as captured by UACR reduction may partly mediate the treatment effect on cardiovascular outcomes (37%), our results show that patients receiving finerenone with 30% or greater reduction in UACR had the lowest incidence of composite cardiovascular outcome events compared with patients receiving placebo .... This indicates that a 30% or greater UACR reduction therapeutic target may also be beneficial to reduce cardiovascular risk,” they wrote.
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