The mineralocorticoid receptor in chronic kidney disease

Chronic kidney disease (CKD) is a major public health concern, affecting approximately 10% of the population worldwide. CKD of glomerular or tubular origin leads to the activation of stress mechanisms, including the renin–angiotensin–aldosterone system and mineralocorticoid receptor (MR) activation....

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Published inBritish journal of pharmacology Vol. 179; no. 13; pp. 3152 - 3164
Main Authors Barrera‐Chimal, Jonatan, Jaisser, Frédéric, Anders, Hans‐Joachim
Format Journal Article
LanguageEnglish
Published England Blackwell Publishing Ltd 01.07.2022
Wiley
Subjects
Aldosterone
Angiotensin
Animal models
Antagonists
cardiorenal
Clinical trials
Diabetes mellitus (non-insulin dependent)
fibrosis
kidney disease
Kidney diseases
Life Sciences
Pharmaceutical sciences
Pharmacology
Public health
Renin
Signal transduction
Therapeutic targets
kidney disease
cardiorenal
fibrosis
aldosterone
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Summary:Chronic kidney disease (CKD) is a major public health concern, affecting approximately 10% of the population worldwide. CKD of glomerular or tubular origin leads to the activation of stress mechanisms, including the renin–angiotensin–aldosterone system and mineralocorticoid receptor (MR) activation. Over the last two decades, blockade of the MR has arisen as a potential therapeutic approach against various forms of kidney disease. In this review, we summarize the experimental studies that have shown a protective effect of MR antagonists (MRAs) in nondiabetic and diabetic CKD animal models. Moreover, we review the main clinical trials that have shown the clinical application of MRAs to reduce albuminuria and, importantly, to slow CKD progression. Recent evidence from the FIDELIO trial showed that the MRA finerenone can reduce hard kidney outcomes when added to the standard of care in CKD associated with type 2 diabetes. Finally, we discuss the effects of MRAs relative to those of SGLT2 inhibitors, as well as the potential benefit of combination therapy to maximize organ protection. LINKED ARTICLES This article is part of a themed issue on Emerging Fields for Therapeutic Targeting of the Aldosterone‐Mineralocorticoid Receptor Signaling Pathway. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.13/issuetoc
Bibliography:Funding information
Frédéric Jaisser and Hans‐Joachim Anders shared senior authorship.
Fondation de France, Grant/Award Number: CARDIO 00086498; Fondation de Recherche sur l’Hypertension Artérielle, Grant/Award Number: REIN/NgalPA ‐ 2017/2018; Deutsche Forschungsgemeinschaft, Grant/Award Number: AN372/30‐1; Agence Nationale de la Recherche, Grant/Award Number: ANR‐19‐CE14‐0013
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SourceType-Scholarly Journals-1
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ObjectType-Review-1
ISSN:0007-1188
1476-5381
DOI:10.1111/bph.15734