Evidence and Uncertainties Surrounding Renin-Guided Medical Therapy for Primary Aldosteronism
Bibliographic record
Abstract
Primary aldosteronism (PA) is a common, yet vastly underdiagnosed, endocrine cause of hypertension. Recent studies report PA prevalence estimates ranging from approximately 10% to 15% in stage 1 hypertension to >20% in resistant hypertension.1,2 PA is characterized by autonomous secretion of aldosterone from one or both adrenal glands in a fashion independent of angiotensin II and often despite concurrent hypokalemia and intravascular volume expansion. Aldosterone binds the mineralocorticoid receptor (MR) of the distal nephron leading to epithelial sodium channel (ENaC)-mediated sodium reabsorption, excretion of potassium and acid, volume expansion, and a corresponding suppression of renin and angiotensin II. The suppression of angiotensin II leads to increased delivery of sodium to the distal nephron thereby perpetuating a vicious pathophysiologic cycle. The chronic sodium retention and volume expansion inherent to PA along with extra-renal MR activation results in heightened cardiovascular risk relative to essential hypertension, even independent of blood pressure.3 Traditionally, treatment recommendations for PA are dictated by whether the source of autonomous aldosterone secretion comes from one adrenal gland (lateralized PA) or both (non-lateralized PA).4 For lateralized PA, surgical adrenalectomy is preferred due to exceedingly high rates of clinical and biochemical “cure” with improved longitudinal cardiovascular outcomes.5,6 For non-lateralized PA (which represents the majority of PA cases), medical therapy with lifelong MR antagonist medications and dietary sodium restriction are advised.4 This treatment approach is also recommended for cases of PA when lateralization testing is unavailable and for lateralized PA patients who are either unwilling or unable to undergo adrenalectomy. Currently, the most commonly used MR antagonists are spironolactone and eplerenone though a number of novel, selective, nonsteroidal MR antagonists as well as aldosterone synthase inhibitors are being developed.7 When prescribing MR antagonists for PA, clinicians are faced with the dilemma of “what is the objective of medical therapy in PA?” Translating the strategy used in essential hypertension, most clinicians aim for blood pressure control (often achieved by combining MR antagonists with other antihypertensive medications) and assume mitigation of hypokalemia as evidence of success. What this approach misses is that mitigating the disproportionately elevated cardiovascular risk inherent to PA should instead be the goal of MR antagonism.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.032 | 0.254 |
| Meta-epidemiology (narrow) | 0.000 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.003 | 0.003 |
| Science and technology studies | 0.002 | 0.005 |
| Scholarly communication | 0.005 | 0.005 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.009 | 0.017 |
| Insufficient payload (model declined to judge) | 0.008 | 0.003 |
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 source (direct Gemma or distilled Codex), 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".