Τίτλος:
Nonsteroidal Mineralocorticoid Receptor Antagonism by Finerenone—Translational Aspects and Clinical Perspectives across Multiple Organ Systems
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Perception of the role of the aldosterone/mineralocorticoid receptor (MR) ensemble has been extended from a previously renal epithelial-centered focus on sodium and volume homeostasis to an understanding of their role as systemic modulators of reactive oxygen species, inflammation, and fibrosis. Steroidal MR antagonists (MRAs) are included in treatment paradigms for resistant hypertension and heart failure with reduced ejection fraction, while more recently, the nonsteroidal MRA finerenone was shown to reduce renal and cardiovascular outcomes in two large phase III trials (FIDELIO-DKD and FIGARO-DKD) in patients with chronic kidney disease and type 2 diabetes, respectively. Here, we provide an overview of the pathophysiologic role of MR overactivation and preclinical evidence with the nonsteroidal MRA finerenone in a range of different disease models with respect to major components of the aggregate mode of action, including interfering with reactive oxygen species generation, inflammation, fibrosis, and hypertrophy. We describe a time-dependent effect of these mechanistic components and the potential modification of major clinical parameters, as well as the impact on clinical renal and cardiovascular outcomes as observed in FIDELIO-DKD and FIGARO-DKD. Finally, we provide an outlook on potential future clinical indications and ongoing clinical studies with finerenone, including a combination study with a sodium–glucose cotransporter-2 inhibitor. © 2022 by the authors.
Συγγραφείς:
Kolkhof, P.
Lawatscheck, R.
Filippatos, G.
Bakris, G.L.
Περιοδικό:
International Journal of Molecular Sciences
Λέξεις-κλειδιά:
finerenone; mineralocorticoid receptor; reactive oxygen metabolite; sodium; sodium glucose cotransporter 2 inhibitor; finerenone; mineralocorticoid antagonist; mineralocorticoid receptor; naphthyridine derivative; reactive oxygen metabolite; sodium, adipose tissue; cardiovascular disease; cardiovascular system; carditis; clinical outcome; combination drug therapy; drug effect; drug indication; drug mechanism; eye; heart muscle fibrosis; heart ventricle hypertrophy; heart ventricle remodeling; human; kidney; kidney disease; kidney fibrosis; lung; nephritis; nonhuman; oxidative stress; pathophysiology; Review; sodium retention; vascular fibrosis; chronic kidney failure; fibrosis; inflammation; non insulin dependent diabetes mellitus, Diabetes Mellitus, Type 2; Fibrosis; Humans; Inflammation; Mineralocorticoid Receptor Antagonists; Naphthyridines; Reactive Oxygen Species; Receptors, Mineralocorticoid; Renal Insufficiency, Chronic; Sodium; Sodium-Glucose Transporter 2 Inhibitors
DOI:
10.3390/ijms23169243
