Steroidal and non-steroidal mineralocorticoid receptor antagonists in cardiorenal medicine.
Cardiorenal
Chronic kidney disease
Finerenone
Mineralocorticoid receptor antagonists
Mineralocorticoids
Journal
European heart journal
ISSN: 1522-9645
Titre abrégé: Eur Heart J
Pays: England
ID NLM: 8006263
Informations de publication
Date de publication:
07 01 2021
07 01 2021
Historique:
received:
15
05
2020
revised:
08
07
2020
accepted:
01
09
2020
pubmed:
26
10
2020
medline:
15
5
2021
entrez:
25
10
2020
Statut:
ppublish
Résumé
This review covers the last 80 years of remarkable progress in the development of mineralocorticoid receptor (MR) antagonists (MRAs) from synthesis of the first mineralocorticoid to trials of nonsteroidal MRAs. The MR is a nuclear receptor expressed in many tissues/cell types including the kidney, heart, immune cells, and fibroblasts. The MR directly affects target gene expression-primarily fluid, electrolyte and haemodynamic homeostasis, and also, but less appreciated, tissue remodelling. Pathophysiological overactivation of the MR leads to inflammation and fibrosis in cardiorenal disease. We discuss the mechanisms of action of nonsteroidal MRAs and how they differ from steroidal MRAs. Nonsteroidal MRAs have demonstrated important differences in their distribution, binding mode to the MR and subsequent gene expression. For example, the novel nonsteroidal MRA finerenone has a balanced distribution between the heart and kidney compared with spironolactone, which is preferentially concentrated in the kidneys. Compared with eplerenone, equinatriuretic doses of finerenone show more potent anti-inflammatory and anti-fibrotic effects on the kidney in rodent models. Overall, nonsteroidal MRAs appear to demonstrate a better benefit-risk ratio than steroidal MRAs, where risk is measured as the propensity for hyperkalaemia. Among patients with Type 2 diabetes, several Phase II studies of finerenone show promising results, supporting benefits on the heart and kidneys. Furthermore, finerenone significantly reduced the combined primary endpoint (chronic kidney disease progression, kidney failure, or kidney death) vs. placebo when added to the standard of care in a large Phase III trial.
Identifiants
pubmed: 33099609
pii: 5936792
doi: 10.1093/eurheartj/ehaa736
pmc: PMC7813624
doi:
Substances chimiques
Mineralocorticoid Receptor Antagonists
0
Mineralocorticoids
0
Spironolactone
27O7W4T232
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
152-161Informations de copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.
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