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Review
. 2023 Dec;55(1):502-513.
doi: 10.1080/07853890.2023.2171110.

Cardiorenal benefits of finerenone: protecting kidney and heart

José R González-Juanatey  1 , Jose Luis Górriz  2 , Alberto Ortiz  3 , Alfonso Valle  4 , Maria Jose Soler  5 , Lorenzo Facila  6
Affiliations
Review

Cardiorenal benefits of finerenone: protecting kidney and heart

José R González-Juanatey et al. Ann Med. 2023 Dec.

Abstract

Persons with diabetes and chronic kidney disease (CKD) have a high residual risk of developing cardiovascular (CV) complications despite treatment with renin-angiotensin system blockers and sodium-glucose cotransporter type 2 inhibitors. Overactivation of mineralocorticoid receptors plays a key role in the progression of renal and CV disease, mainly by promoting inflammation and fibrosis. Finerenone is a nonsteroidal selective mineralocorticoid antagonist. Recent clinical trials, such as FIDELIO-DKD and FIGARO-DKD and the combined analysis FIDELITY have demonstrated that finerenone decreases albuminuria, risk of CKD progression, and CV risk in subjects with type 2 diabetes (T2D) and CKD. As a result, finerenone should thus be considered as part of a holistic approach to kidney and CV risk in persons with T2D and CKD. In this narrative review, the impact of finerenone treatment on the CV system in persons with type 2 diabetes and CKD is analyzed from a practical point of view.Key messages:Despite inhibition of renin-angiotensin system and sodium-glucose cotransporter type 2, persons with type 2 diabetes (T2D) and chronic kidney disease (CKD) remain on high cardiovascular (CV) residual risk.Overactivation of mineralocorticoid receptors plays a key role in the progression of renal and CV disease, mainly by promoting inflammation and fibrosis that is not targeted by traditional treatments.Finerenone is a nonsteroidal selective mineralocorticoid antagonist that decreases not only albuminuria, but also the risk of CKD progression, and CV risk in subjects with T2D and CKD.

Keywords: Albuminuria; cardiovascular; chronic kidney disease; finerenone; inflammation; type 2 diabetes.

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Conflict of interest statement

AO research is supported by Instituto de Salud Carlos III (ISCIII) RICORS program to RICORS2040 (RD21/0005/0001) and SPACKDc PMP21/00109, FEDER funds. MJS research is supported by Instituto de Salud Carlos III (ISCIII) RICORS program to RICORS2040 (RD21/0005/0016) and Marató TV3 2020 421/C/2020, Marató TV3 2021 215/C/2021, (PI21/01292) FEDER funds, and EIN2020-1123381.

JRGJ reports fees for conferences and for participating in Bayer’s advisory council.

JLG reports personal fees from NovoNordisk (Fees, Advisory), Boehringer (Fees, Advisory and Consulting), Eli Lilly (Fees), AstraZeneca (Fees, Advisory and Grants), Esteve (Fees), Bayer (Fees, Advisory and Consulting) and Vifor (fees and advice).

AO has received grants from Sanofi and consultancy or speaker fees or travel support from Advicciene, Astellas, Astrazeneca, Amicus, Amgen, Fresenius Medical Care, GSK, Bayer, Sanofi-Genzyme, Menarini, Mundipharma, Kyowa Kirin, Alexion, Freeline, Idorsia, Chiesi, Otsuka, Novo-Nordisk, Sysmex and Vifor Fresenius Medical Care Renal Pharma and is Director of the Catedra Mundipharma-UAM of kidney disease and diabetes and the Catedra Astrazeneca-UAM of chronic kidney disease and electrolytes.

MJS has received personal fees from NovoNordisk (fees, consulting), Janssen (fees), Boehringer (fees, consulting, grants and consulting), Eli Lilly (fees), AstraZeneca (fees and consulting), Esteve (fees), Fresenius Medical Care (fees), Mundipharma (fees and advice), NovoNordisk (fees, advice and advice), Bayer (fees, advice and advice), Travere Therapeutics (fees and advice), GE Healthcare (advice) and Vifor (fees and advice). MJS is also the editor in chief of the Clinical Kidney Journal.

AV has received honoraria for presentations from Bayer, Boehringer-Ingelheim, Daiichi Sankyo, and Pfizer-BMS.

MJS has received personal fees from NovoNordisk (fees, consulting), Janssen (fees), Boehringer (fees, consulting, grants and consulting), Eli Lilly (fees), AstraZeneca (fees and consulting), Esteve (fees), Fresenius Medical Care (fees), Mundipharma (fees and advice), NovoNordisk (fees, advice and advice), Bayer (fees, advice and advice), Travere Therapeutics (fees and advice), GE Healthcare (advice) and Vifor (fees and advice). MJS is also the editor in chief of the Clinical Kidney Journal.

LF has received fees from Novonordisk, Boehringer, AstraZeneca, Bayer, Esteve, Eli Lilly.

Figures

Figure 1.
Figure 1.
Mechanisms of action of ACE inhibitors/ARB, SGLT2 inhibitors and MRA on kidneys. ARB: angiotensin receptor blockers; ACE: angiotensin converting enzyme; SGLT2: sodium-glucose cotransporter type 2; MRA: mineralocorticoid receptor antagonists. Figure made with reference data [19,24–27].
Figure 2.
Figure 2.
Consequences of hyperactivation of the mineralocorticoid receptor in persons with chronic kidney disease and diabetes. MR: mineralocorticoid receptor; T2D: type 2 diabetes. Figure was made with reference data [4,19–22,32,33].
Figure 3.
Figure 3.
General characteristics of the FIDELIO-DKD and FIGARO-DKD studies. UACR: urine albumin-creatinine ratio; CV: cardiovascular; CKD: chronic kidney disease; eGFR: estimated glomerular filtration rate; HFrEF: heart failure with reduced ejection fraction; MI: myocardial infarction; SBP: systolic blood pressure. Figure made with data from the references [29,30].
Figure 4.
Figure 4.
Relative risk reduction of main cardiovascular outcomes (finerenone vs. placebo) of the combined analysis of FIDELITY study. *Time to first CV death, nonfatal MI, non-fatal stroke, or HF hospitalization. CV: cardiovascular; HF: heart failure; MI: myocardial infarction; HR: Hazard ratio; 95% CI: 95% confidence interval. Figure made with reference data [31].
Figure 5.
Figure 5.
Primary cardiovascular endpoint* in the FIGARO-DKD study, depending on baseline treatment with SGLT2 inhibitors. *Death from cardiovascular causes, non-fatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. CI: confidence interval; HR: Hazard ratio; SGLT2i: SGLT2 inhibitors. Figure made with reference data [30].
See this image and copyright information in PMC

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