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A Podcast Discussing Aldosterone and Mineralocorticoid Receptor Antagonists in 2021: A Paradigm Shift

The classic focus on the mechanisms of action of aldosterone was directed primarily on its role in modulating renal excretory function and maintaining volume homeostasis. In contrast, many recent studies have demonstrated a much wider and expanded role for aldosterone and for the mineralocorticoid r...

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Autor principal: Epstein, Murray
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Healthcare 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8991300/
https://www.ncbi.nlm.nih.gov/pubmed/35294746
http://dx.doi.org/10.1007/s13300-022-01236-w
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author Epstein, Murray
author_facet Epstein, Murray
author_sort Epstein, Murray
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description The classic focus on the mechanisms of action of aldosterone was directed primarily on its role in modulating renal excretory function and maintaining volume homeostasis. In contrast, many recent studies have demonstrated a much wider and expanded role for aldosterone and for the mineralocorticoid receptor (MR). Activation of the MR promotes inflammation, collagen formation, fibrosis, and necrosis with consequent renal injury. Increasing evidence has accrued that implicates the pathophysiological overactivation of the MR as a major determinant of progression of both diabetic and nondiabetic chronic kidney disease (CKD). By promoting cascades of injury encompassing inflammation and fibrosis, MR overactivation constitutes a pivotal determinant of CKD progression and consequently its associated morbidity and mortality. Based on this mechanism of action, blockade of the MR with the nonsteroidal MR antagonist finerenone is currently being investigated as a novel treatment regimen to slow the progression of CKD. The recently reported FIDELIO-DKD (FInerenone in reducing kiDnEy faiLure and dIsease prOgression in Diabetic Kidney Disease) study demonstrated that patients with CKD and type 2 diabetes (T2D) who were treated with finerenone manifested a lower risk of a composite primary outcome event compared with patients in the placebo arm (defined as kidney failure or a sustained decrease of ≥ 40% in the estimated glomerular filtration rate from baseline, or death from renal causes). In addition, patients in the finerenone group also manifested a lower risk of a key secondary outcome event (defined as death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure). Based on the success of these major clinical trials, finerenone was approved by the FDA on 9 July 2021 as a novel treatment for retarding CKD progression in patients with T2D (https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-drug-reduce-risk-serious-kidney-and-heart-complications-adults-chronic-kidney-disease). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13300-022-01236-w.
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spelling pubmed-89913002022-04-22 A Podcast Discussing Aldosterone and Mineralocorticoid Receptor Antagonists in 2021: A Paradigm Shift Epstein, Murray Diabetes Ther Commentary The classic focus on the mechanisms of action of aldosterone was directed primarily on its role in modulating renal excretory function and maintaining volume homeostasis. In contrast, many recent studies have demonstrated a much wider and expanded role for aldosterone and for the mineralocorticoid receptor (MR). Activation of the MR promotes inflammation, collagen formation, fibrosis, and necrosis with consequent renal injury. Increasing evidence has accrued that implicates the pathophysiological overactivation of the MR as a major determinant of progression of both diabetic and nondiabetic chronic kidney disease (CKD). By promoting cascades of injury encompassing inflammation and fibrosis, MR overactivation constitutes a pivotal determinant of CKD progression and consequently its associated morbidity and mortality. Based on this mechanism of action, blockade of the MR with the nonsteroidal MR antagonist finerenone is currently being investigated as a novel treatment regimen to slow the progression of CKD. The recently reported FIDELIO-DKD (FInerenone in reducing kiDnEy faiLure and dIsease prOgression in Diabetic Kidney Disease) study demonstrated that patients with CKD and type 2 diabetes (T2D) who were treated with finerenone manifested a lower risk of a composite primary outcome event compared with patients in the placebo arm (defined as kidney failure or a sustained decrease of ≥ 40% in the estimated glomerular filtration rate from baseline, or death from renal causes). In addition, patients in the finerenone group also manifested a lower risk of a key secondary outcome event (defined as death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure). Based on the success of these major clinical trials, finerenone was approved by the FDA on 9 July 2021 as a novel treatment for retarding CKD progression in patients with T2D (https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-drug-reduce-risk-serious-kidney-and-heart-complications-adults-chronic-kidney-disease). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13300-022-01236-w. Springer Healthcare 2022-03-16 2022-04 /pmc/articles/PMC8991300/ /pubmed/35294746 http://dx.doi.org/10.1007/s13300-022-01236-w Text en © The Author(s) 2022 https://creativecommons.org/licenses/by-nc/4.0/Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Commentary
Epstein, Murray
A Podcast Discussing Aldosterone and Mineralocorticoid Receptor Antagonists in 2021: A Paradigm Shift
title A Podcast Discussing Aldosterone and Mineralocorticoid Receptor Antagonists in 2021: A Paradigm Shift
title_full A Podcast Discussing Aldosterone and Mineralocorticoid Receptor Antagonists in 2021: A Paradigm Shift
title_fullStr A Podcast Discussing Aldosterone and Mineralocorticoid Receptor Antagonists in 2021: A Paradigm Shift
title_full_unstemmed A Podcast Discussing Aldosterone and Mineralocorticoid Receptor Antagonists in 2021: A Paradigm Shift
title_short A Podcast Discussing Aldosterone and Mineralocorticoid Receptor Antagonists in 2021: A Paradigm Shift
title_sort podcast discussing aldosterone and mineralocorticoid receptor antagonists in 2021: a paradigm shift
topic Commentary
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8991300/
https://www.ncbi.nlm.nih.gov/pubmed/35294746
http://dx.doi.org/10.1007/s13300-022-01236-w
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