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Arian Mansur

Pronouns

He/Him/His

Job Title

Research Trainee

Academic Rank

Department

Medicine

Authors

Arian Mansur, Anand Vaidya, Alexander Turchin

Principal Investigator

Alexander Turchin

Research Category: Cardiovascular, Diabetes, and Metabolic Disorders

Tags

Using Renin Activity to Guide Mineralocorticoid Antagonist Therapy in Patients with Low-Renin Hypertension

Scientific Abstract

A significant proportion of patients with hypertension have low/suppressed renin. The aim of this study was to determine whether treatment with a mineralocorticoid receptor agonist (MRA) dosed to achieve unsuppressed renin is associated with a decrease in blood pressure and/or proteinuria in patients with low-renin hypertension (LRH). A retrospective single-center cohort study of adults with hypertension with suppressed (<1.0 ng/mL/h) plasma renin activity (PRA) and detectable aldosterone levels between 2005 and 2021 was conducted. All patients were treated with spironolactone (women) or eplerenone (men), gradually increasing the dose to target a PRA ≥1.0 ng/ml/h or the maximum tolerated dose. Of 39 patients studied, 32 (82.1%) achieved unsuppressed renin. Systolic and diastolic blood pressure decreased from 148.0 and 81.2 to 125.8 and 71.6 mmHg, respectively (Ps<0.001). Similar findings were seen in patients with high (>10 ng/dL) or low (<10 ng/dL) aldosterone levels. 24 (61.5%) patients had ≥1 baseline anti-hypertensive medication stopped. Among six patients who had detectable proteinuria, the mean albumin-to-creatinine ratio decreased from 179.0 to 36.1 mg/g (P=0.03). No patient had to stop treatment due to adverse reactions. Our findings suggest that MRA therapy to target unsuppressed renin can safely and effectively improve blood pressure control and reduce proteinuria.

Lay Abstract

Hypertension is a highly common chronic disease that affects over 1 billion people worldwide. Primary aldosteronism is increasingly recognized as a significant cause of hypertension that occurs when the adrenal glands produce too much aldosterone. In most healthy people aldosterone production is induced by the hormone renin. However, emerging studies have shown that there are also many hypertensive patients with low renin who experience renin-independent aldosterone production. While mineralocorticoid receptor antagonist (MRA) therapy to induce an increase in renin is associated with improved outcomes in primary aldosteronism, it is unknown whether MRA therapy is beneficial in patients with low-renin hypertension. We therefore conducted a prospective observational study to determine whether hypertensive patients with suppressed renin levels and detectable aldosterone levels benefit from MRA therapy. We studied 39 patients treated between 2005 and 2021. We found that in patients who had their renin levels unsuppressed after MR blockade experienced significant decreases in their blood pressure and urine protein (an indicator of kidney damage). These findings suggest that suppressed renin may be sufficient to identify patients who could benefit from MR blockade, and that dosing MR antagonists to achieve unsuppressed renin could lower both elevated blood pressure and proteinuria.

Clinical Implications

For patients with low-renin hypertension, treatment with a mineralocorticoid receptor antagonist, titrated to achieve unsuppressed renin, should be considered.