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Finerenone in Cardiorenal Disease: A Narrative Review of Molecular Mechanisms, Clinical Evidence, and Emerging
Giulio Geraci1,2, Nicola Sinatra3, Valentina Paternò2
1Department of Medicine and Surgery, "Kore" University of Enna, Enna, Italy.
Abstract:
Cardiorenal disease reflects a tightly interconnected pathophysiological continuum driven by neurohormonal activation, inflammation, oxidative stress, and progressive fibrosis. Among these mechanisms, mineralocorticoid receptor (MR) overactivation has emerged as a central mediator of cardiac and renal injury independent of blood pressure effects. Finerenone, a non-steroidal selective MR antagonist, exhibits distinct pharmacological properties compared with steroidal MR antagonists, including enhanced receptor selectivity, balanced cardiac and renal tissue distribution, and differential cofactor modulation that translates into potent anti-inflammatory and antifibrotic activity with an improved safety profile.Large outcome trials have established finerenone as an effective cardiorenal protective therapy. The FIDELIO-DKD and FIGARO-DKD trials demonstrated significant reductions in kidney disease progression and cardiovascular events in patients with type 2 diabetes and chronic kidney disease, with consistent benefits confirmed in the pooled FIDELITY analysis. More recently, the FINEARTS-HF trial extended these benefits to patients with heart failure with mildly reduced or preserved ejection fraction regardless of diabetes status. Across trials, hyperkalemia was infrequent when structured monitoring strategies were applied.Beyond established indications, emerging data suggest potential systemic effects on retinal and hepatic outcomes, while ongoing studies are evaluating finerenone in non-diabetic chronic kidney disease. Subgroup analyses consistently demonstrate preserved efficacy and favorable safety when finerenone is combined with sodium-glucose cotransporter-2 inhibitors, supporting complementary disease-modifying strategies.This review integrates molecular mechanisms, clinical trial evidence, systemic effects, and therapeutic positioning of finerenone within contemporary cardiorenal care, highlighting its expanding role in multidrug approaches targeting the cardiovascular-renal-metabolic axis.
Insights
Finerenone, a selective mineralocorticoid receptor antagonist, effectively protects against cardiorenal disease progression and cardiovascular events in patients with type 2 diabetes and chronic kidney disease. Its benefits extend to heart failure patients, with a favorable safety profile.
Area of Science:
- Cardiology
- Nephrology
- Pharmacology
Background:
- Cardiorenal disease involves interconnected pathways like neurohormonal activation and fibrosis.
- Mineralocorticoid receptor (MR) overactivation is a key driver of cardiac and renal injury.
- Finerenone is a novel non-steroidal selective MR antagonist with anti-inflammatory and antifibrotic properties.
Purpose of the Study:
- To review the molecular mechanisms, clinical evidence, and therapeutic role of finerenone in cardiorenal disease.
- To highlight finerenone's efficacy and safety in various patient populations.
- To discuss its positioning within contemporary cardiorenal care strategies.
Main Methods:
- Review of large outcome trials including FIDELIO-DKD, FIGARO-DKD, and FINEARTS-HF.
- Analysis of pooled data and subgroup findings.
- Integration of molecular data and clinical evidence.
Main Results:
- Finerenone significantly reduced kidney disease progression and cardiovascular events in patients with type 2 diabetes and CKD.
- Benefits were observed in heart failure patients (mildly reduced/preserved ejection fraction) regardless of diabetes status.
- Hyperkalemia was infrequent with structured monitoring; favorable safety profile noted.
Conclusions:
- Finerenone is an effective cardiorenal protective therapy with established indications.
- Emerging data suggest broader systemic benefits and potential use in non-diabetic CKD.
- Finerenone shows synergistic effects with SGLT2 inhibitors, supporting combination therapies for the cardiovascular-renal-metabolic axis.
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