Aldosterone Synthase Inhibitors for Cardiorenal Protection: Ready for Prime Time?

Abstract: Background: Aldosterone is the principal mineralocorticoid hormone and the final effector of the renin-angiotensin-aldosterone system. This hormone is primarily synthesized by the CYP11B2 enzyme and produced by the adrenal zona glomerulosa. Through genomic and non-genomic effects, it plays an important role in cardiovascular and renal disease. To counteract aldosterone-mediated damage, steroidal mineralocorticoid receptor antagonists are recommended by international guidelines, but endocrine side effects often limit their use in a substantial proportion of patients. Conversely, nonsteroidal mineralocorticoid receptor antagonists, with an improved selectivity and safety profile, are gaining a prominent position among therapeutic pillars. However, blocking the mineralocorticoid receptors does not completely inhibit aldosterone effects because of escape mechanisms and non-genomic activity. Thus, inhibiting aldosterone synthesis could be a promising strategy to prevent aldosterone-mediated cardiorenal damage. The limited specificity for CYP11B2 and side effects due to off-target activity hampered the development of first-generation aldosterone synthase inhibitors (ASIs). Summary: The development of highly specific ASIs led to successful clinical trials in patients with resistant and uncontrolled hypertension. Additionally, a recent randomized clinical trial showed a significant benefit of ASIs in patients with chronic kidney disease and albuminuria. Key Messages: The strength of the clinical evidence collected so far is still limited, and larger outcome-based clinical trials are needed to confirm the promising role of ASIs in cardiorenal damage.

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch

Erschienen in
Aldosterone Synthase Inhibitors for Cardiorenal Protection: Ready for Prime Time? ; volume:49 ; number:1 ; year:2024 ; pages:1041-1056 ; extent:16
Kidney & blood pressure research ; 49, Heft 1 (2024), 1041-1056 (gesamt 16)

Urheber
Mazzieri, Alessio
Timio, Francesca
Patera, Francesco
Trepiccione, Francesco
Bonomini, Mario
Reboldi, Gianpaolo

DOI
10.1159/000542621
URN
urn:nbn:de:101:1-2412260154034.863580064170
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
15.08.2025, 07:25 MESZ

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Beteiligte

  • Mazzieri, Alessio
  • Timio, Francesca
  • Patera, Francesco
  • Trepiccione, Francesco
  • Bonomini, Mario
  • Reboldi, Gianpaolo

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