Aldosterone, Mineralocorticoid Receptor Activation, and CKD: A Review of Evolving Treatment Paradigms

Nutrient-derived modification of mineral corticoid receptors is relevant to diabetic kidney disease progression

“…Furthermore, MR activation has been shown to be regulated by either coregulators or posttranslational modifications, such as phosphorylation, acetylation, ubiquitination, sumoylation, and oxidation. These data suggest that MR activation plays an essential role in the homeostasis of organs through fine-tuning at several levels (e.g., ligand production or degradation, nonligand activation, posttranslational modification of MR) [7].…”

“…Heavy proteinuric (>2 g/24-h) kidney disease patients were found to display prominent kidney scarring with a significant 5-fold increase in MR levels [6]. In addition to ligand (mineralocorticoid)-induced activation, MR can be activated by nonligand activation with the regulatory protein Rac family small guanosine triphosphatase 1 (Rac1), oxidative stress, elevated glucose, or high salt levels [7]. Furthermore, MR activation has been shown to be regulated by either coregulators or posttranslational modifications, such as phosphorylation, acetylation, ubiquitination, sumoylation, and oxidation.…”

Consenso de la Sociedad Latinoamericana de Nefrología e Hipertensión en relación con el papel de los antagonistas del receptor mineralocorticoide en enfermedad renal crónica

“…Actualmente no hay evidencia contundente del uso de finerenona en la ERC de etiología no diabética, sin embargo, se está llevando a cabo el estudio FIND-CKD (Clinicaltrials.gov identificador NCT05047263), el cual tendrá como objetivo primario evaluar finerenona en progresión de enfermedad renal en paciente adultos con ERC (diabética y no diabética) con albuminuria 49 .…”

“…No existe evidencia clínica contundente que soporte el uso de ARM en ERD con fenotipo no albuminúrico 49 .…”

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

“…For these cases, antagonists of the mineralocorticoid receptor (MR), a major receptor for aldosterone, are recommended owing to their efficacy in controlling both blood pressure and disease progression [3]. Although traditional steroidal MR antagonists (spironolactone and eplerenone) have certain limitations with respect to their low selectivity and affinity for MR, respectively, novel highly selective and potent MR antagonists (esaxerenone and finerenone) have been developed for the treatment of hypertension and diabetic kidney disease [4]. An alternative approach to suppressing the activity of aldosterone involves the inhibition of aldosterone synthase (AS; CYP11B2).…”