Aldosterone synthase inhibition: a novel bullet to fight cardiovascular–kidney–metabolic syndrome
Bibliographic record
Abstract
Aldosterone is synthesized by the CYP11B2 enzyme, primarily in the zona glomerulosa of the adrenal gland. It exerts its classical effects on sodium and water balance in the renal distal nephron through binding to the mineralocorticoid receptor (MR). Excess aldosterone production or overactivation of the MR outside the distal nephron leads to cardiac, renal, and vascular injury by increasing oxidative stress and activating the inflammatory and fibrotic pathways. MR antagonists (MRAs) have proved effective at decreasing organ damage and the deleterious effects of excess aldosterone/MR activation. However, MRAs do not fully block the non-genomic effects of aldosterone, which may contribute to residual risks. CYP11B2 inhibition has emerged as an additional therapeutic approach to decreasing the deleterious genomic and non-genomic effects of aldosterone. The development of specific aldosterone synthase inhibitors (ASi) has proved challenging due to the considerable similarity between aldosterone synthase and 11β-hydroxylase, an enzyme encoded by the CYP11B1 gene that catalyzes cortisol synthesis. In this review, we summarize the latest developments on preclinical evidence and clinical trials for ASi and explore the potential clinical advantages of ASi.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".