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

BACKGROUND: Mineralocorticoid receptor antagonists (MRAs) are often empirically used for patients with low-renin hypertension (LRH) or probable primary aldosteronism (PA) who decline surgery. However, the optimal approach to MRA therapy is unknown. Studies have shown that a rise in renin is an effective biomarker of prevention of cardiovascular complications of PA. This study aimed to determine whether empiric MRA therapy in patients with LRH or probable PA targeting unsuppressed renin is associated with a decrease in blood pressure and/or proteinuria. METHODS: Retrospective single-center cohort study from 2005 to 2021 included adults with LRH or probable PA (renin activity <1.0 ng/ml/h and detectable aldosterone levels). All patients were empirically treated with an MRA, targeting renin ≥1.0 ng/ml/h. RESULTS: Out 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 mm Hg, respectively (P < 0.001 for both). Similar blood pressure reductions were seen whether patients had high (>10 ng/dl) or low (<10 ng/dl) aldosterone levels. The majority (24/39; 61.5%) of patients had at least one baseline anti-hypertensive medication stopped. Among the six patients who had detectable proteinuria and albumin-to-creatinine (ACR) measurements post-treatment, the mean ACR decreased from 179.0 to 36.1 mg/g (P = 0.03). None of the patients studied had to completely stop treatment due to adverse reactions. CONCLUSIONS: Empiric MRA therapy in patients with LRH or probable PA targeting unsuppressed renin can safely and effectively improve blood pressure control and reduce proteinuria.