Inhibition of aldosterone synthase: Does this offer advantages compared with the blockade of mineralocorticoid receptors?

Ando, Hitoshi

doi:10.1038/s41440-023-01188-z

Cited by 6 publications

(6 citation statements)

References 11 publications

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“…Beyond MRAs, the selective aldosterone synthase inhibitors (ASI) is emerging as a new class of drugs, specifically targeting aldosterone synthesis upstream of the MR [80]. MR is not only activated by aldosterone, but also by cortisol, and by not specific stimuli such as hyperglycemia, high salt intake, and oxidative stress.…”

Section: Mineralcorticoid Receptor Antagonistsmentioning

confidence: 99%

Molecular Targets of Novel Therapeutics for Diabetic Kidney Disease: A New Era of Nephroprotection

Mazzieri,

Porcellati,

Timio

et al. 2024

IJMS

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Diabetic kidney disease (DKD) is a chronic microvascular complication in patients with diabetes mellitus (DM) and the leading cause of end-stage kidney disease (ESKD). Although glomerulosclerosis, tubular injury and interstitial fibrosis are typical damages of DKD, the interplay of different processes (metabolic factors, oxidative stress, inflammatory pathway, fibrotic signaling, and hemodynamic mechanisms) appears to drive the onset and progression of DKD. A growing understanding of the pathogenetic mechanisms, and the development of new therapeutics, is opening the way for a new era of nephroprotection based on precision-medicine approaches. This review summarizes the therapeutic options linked to specific molecular mechanisms of DKD, including renin-angiotensin-aldosterone system blockers, SGLT2 inhibitors, mineralocorticoid receptor antagonists, glucagon-like peptide-1 receptor agonists, endothelin receptor antagonists, and aldosterone synthase inhibitors. In a new era of nephroprotection, these drugs, as pillars of personalized medicine, can improve renal outcomes and enhance the quality of life for individuals with DKD.

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Section: Mineralcorticoid Receptor Antagonistsmentioning

confidence: 99%

Molecular Targets of Novel Therapeutics for Diabetic Kidney Disease: A New Era of Nephroprotection

Mazzieri,

Porcellati,

Timio

et al. 2024

IJMS

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“…A different promising mechanism of RAASi is the inhibition of aldosterone synthase (Asi). At variance with MRAs which target to mitigate the effects of aldosterone, Asis act one step earlier by inhibiting the production of aldosterone itself [59]. Baxdrostat is a highly selective Asi, with no impact on cortisol secretion, that has shown promising results in the treatment of resistant hypertension [60].…”

Section: Aldosterone Synthase Inhibitorsmentioning

confidence: 99%

“…APA is a central enzyme converting angiotensin II to angiotensin III in the brain. Angiotensin III can increase blood pressure by increasing vasopressin release which inhibits diuresis, stimulating sympathetic tone and vascular resistance as well as stimulating baroreflex function [59]. Therefore, the inhibition of APA is meant to block all these mechanisms and decrease systemic blood pressure.…”

Section: Aminopeptidase a Inhibitorsmentioning

confidence: 99%

Renin–Angiotensin–Aldosterone System: From History to Practice of a Secular Topic

Ksiazek,

Hu,

Andò

et al. 2024

IJMS

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Renin–angiotensin–aldosterone system (RAAS) inhibitors are standard care in patients with hypertension, heart failure or chronic kidney disease (CKD). Although we have studied the RAAS for decades, there are still circumstances that remain unclear. In this review, we describe the evolution of the RAAS and pose the question of whether this survival trait is still necessary to humankind in the present age. We elucidate the benefits on cardiovascular health and kidney disease of RAAS inhibition and present promising novel medications. Furthermore, we address why more studies are needed to establish a new standard of care away from generally prescribing ACEi or ARB toward an improved approach to combine drugs tailored to the needs of individual patients.

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“…Aldosterone synthase inhibitors may decrease all genomic and non-genomic actions of aldosterone, including non-genomic actions not mediated by the MR [ 126 ]. To what extent they may have advantages and improve outcomes over available MRAs remains unclear [ 127 ]. In the phase 2 BrigHTN trial, 248 participants with treatment-resistant hypertension (BP ≥130/80 mmHg and receiving a diuretic and at least two other antihypertensive drugs) were randomized to the aldosterone synthase inhibitor baxdrostat (0.5–2.0 mg/day) or placebo.…”

Section: Mras Versus Aldosterone Synthase Inhibitorsmentioning

confidence: 99%

Mineralocorticoid receptor antagonist use in chronic kidney disease with type 2 diabetes: a clinical practice document by the European Renal Best Practice (ERBP) board of the European Renal Association (ERA)

Sarafidis

Iatridi

Ferro

et al. 2023

Clinical Kidney Journal

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Chronic kidney disease (CKD) in individuals with type 2 diabetes (T2D) represents a major public health issue; it develops in about 30-40% of patients with diabetes mellitus and is the commonest cause of CKD worldwide. Patients with CKD and T2D are at high risk of both developing kidney failure and of cardiovascular events. Renin-angiotensin system (RAS) blockers were considered the cornerstone of treatment of albuminuric CKD in T2D for more than 20 years. However, the residual risk of progression to more advanced CKD stages under RAS blockade remains high, while in major studies with these agents in patients with CKD and T2D no significant reductions in cardiovascular events and mortality were evident. Steroidal mineralocorticoid receptor antagonists (MRAs) are known to reduce albuminuria in individuals on RAS monotherapy, but their wide clinical use has been curtailed by the significant risk of hyperkalemia and absence of trials with hard renal outcomes. In recent years, non-steroidal MRAs have received increasing interest due to better pharmacologic profile. Finerenone, the first compound of this class, was shown to effectively reduce the progression of kidney disease and of cardiovascular outcomes in participants with T2D in phase 3 trials. This clinical practice document prepared from a task force of the European Renal Best Practice (ERBP) board summarizes current knowledge on the role of MRAs in the treatment of CKD in T2D aiming to support clinicians in decision-making and everyday management of patients with this condition.

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Inhibition of aldosterone synthase: Does this offer advantages compared with the blockade of mineralocorticoid receptors?

Cited by 6 publications

References 11 publications

Molecular Targets of Novel Therapeutics for Diabetic Kidney Disease: A New Era of Nephroprotection

Molecular Targets of Novel Therapeutics for Diabetic Kidney Disease: A New Era of Nephroprotection

Renin–Angiotensin–Aldosterone System: From History to Practice of a Secular Topic

Mineralocorticoid receptor antagonist use in chronic kidney disease with type 2 diabetes: a clinical practice document by the European Renal Best Practice (ERBP) board of the European Renal Association (ERA)

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