Finerenone in Cardiorenal Disease: A Narrative Review of Molecular Mechanisms, Clinical Evidence, and Emerging Therapeutic Roles

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.

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Journal
Cardiovascular Drugs and Therapy
Published
2026-05-22
DOI
https://doi.org/10.1007/s10557-026-07890-7
Primary Topic
Hormonal Regulation and Hypertension
Type
article
Field-Weighted Citation Impact
0.00

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article

Finerenone in Cardiorenal Disease: A Narrative Review of Molecular Mechanisms, Clinical Evidence, and Emerging Therapeutic Roles

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Cardiovascular Drugs and Therapy
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article

Finerenone in Cardiorenal Disease: A Narrative Review of Molecular Mechanisms, Clinical Evidence, and Emerging Therapeutic Roles

Giuliano Cassataro, Giulio Geraci, Vincenzo Calabrese, Giuseppe Cuttone, Riccardo Polosa, Roberta Esposito, Nicola Sinatra, Giacomo Pucci, Caterina Carollo, Calogero Geraci, Valentina Paternò, Luca Zanoli, Pietro Ferrara, Costantino Mancusi, Giuseppe Mulè
article en

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.

Cardiovascular Drugs and Therapy
Università degli Studi di Enna Kore (IT), University of Perugia (IT), Santa Maria Nuova Hospital (IT), University of Catania (IT), Department of Health (ES), Federico II University Hospital (IT), Gibraltar Health Authority (GI), Fondazione Istituto G. Giglio di Cefalù (IT), IRCCS Istituto Auxologico Italiano (IT), Nini Hospital (LB), Ospedale San Bortolo (IT), Ospedali Riuniti Umberto I (IT), University of Milano-Bicocca (IT), University of Naples Federico II (IT), University of Palermo (IT)
Università degli Studi di Milano-Bicocca
Good health and well-being
Openalex Percentile: Top 6%
Hormonal Regulation and Hypertension
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