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Phase 3 FIND-CKD data show finerenone slows kidney decline and reduces CV events in adults with nondiabetic CKD, Rajiv Agarwal, MD, adds his perspective.
Finerenone (Kerendia), a nonsteroidal mineralocorticoid receptor antagonist (MRA) already approved for chronic kidney disease (CKD) linked to type 2 diabetes, slowed the rate of kidney function decline in adults with CKD who did not have diabetes, according to results of the phase 3 FIND-CKD trial published in the New England Journal of Medicine.
Rajiv Agarwal, MD, professor emeritus of medicine at Indiana University School of Medicine and staff physician at the Richard L. Roudebush VA Medical Center, frames finerenone as completing a trio of complementary mechanisms: RAS inhibitors work hemodynamically, SGLT2 inhibitors act on tubular and metabolic pathways, and finerenone targets inflammation and fibrosis. Together, he said, they may now function as 3 distinct pillars of CKD care.
Agarwal and colleagues randomly assigned 1584 adults with CKD and albuminuria who were already taking a renin–angiotensin system (RAS) inhibitor to finerenone, 10 or 20 mg daily, or placebo.
At baseline, participants had an eGFR of 25 to less than 90 mL/min/1.73 m² and a urinary albumin-to-creatinine ratio of 200 to 3500, with a similar mean baseline eGFR between groups, at roughly 47 mL/min/1.73 m².
Over 32 months, the mean annual rate of change in eGFR, the trial's primary outcome, was −3.3 mL/min/1.73 m² with finerenone compared with −4.0 mL/min/1.73 m² with placebo, a difference of 0.7 mL/min/1.73 m² (95% CI, 0.3-1.1; P < .001).
A prespecified hierarchical analysis also showed a reduced risk of a composite kidney or cardiovascular outcome, defined as a sustained eGFR decline of at least 57%, kidney failure, heart failure hospitalization, or cardiovascular death, with finerenone versus placebo (hazard ratio, 0.77; 95% CI, 0.60-0.99; P = .04).
In FIND-CKD alone, the cardiovascular composite trended favorably but did not reach statistical significance on its own (hazard ratio, 0.60; 95% CI, 0.27-1.33). A larger pooled analysis, Infinity, combining FIND-CKD with finerenone's prior diabetic CKD trials, filled in that picture: heart failure hospitalization and cardiovascular death were each independently, statistically significant, with reductions of 22% and 18%, respectively.
Notably, cardiovascular death reached nominal significance in the pooled analysis after narrowly missing it in an earlier pooled analysis limited to diabetic CKD trials (P = .076). Agarwal said this pattern, along with a parallel signal for all-cause mortality, represents a mortality benefit worth continued follow-up, since both cardiovascular and all-cause mortality comparisons were nominally significant across the pooled cohort.
Agarwal said the Infinity data support positioning finerenone as a foundational therapy to be layered in early alongside RAS and SGLT2 inhibitors, rather than reserved as a later-line option.
Finerenone selectively blocks the mineralocorticoid receptor, a pathway implicated in inflammation and fibrosis across multiple kidney disease etiologies, independent of glycemic status.
The agent was first approved by the FDA in 2021 for adults with CKD associated with type 2 diabetes, based on the FIDELIO-DKD trial, which showed reduced risk of CKD progression and cardiovascular events compared with placebo in that population.
FIND-CKD extends that evidence base to CKD without diabetes, a population that historically has had fewer disease-modifying options despite representing a substantial share of overall CKD cases.
Only about 17% of FIND-CKD participants were using an SGLT2 inhibitor at baseline, leaving the finerenone–SGLT2 inhibitor combination in nondiabetic CKD an open question.
Of the roughly 14,500 participants in the Infinity pooled analysis, only about 1500 came from FIND-CKD itself, meaning the hard-outcome evidence in nondiabetic CKD still leans heavily on the diabetic trials within the pool. Agarwal pointed to a need for prospective combination data, including potassium and volume effects, adequately powered biopsy-confirmed studies in IgA nephropathy and FSGS, longer-term safety and durability data, and biomarker work to identify which patients benefit most.
Editor’s Note: Agarwal reports relevant disclosures with Alexion Pharmaceuticals, Inc. AstraZeneca, Bayer HealthCare Pharmaceuticals Inc., Boehringer Ingelheim, and others.
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