Low-renin hypertension: a distinct phenotype enabling mechanism-based treatment

Low-renin hypertension is increasingly recognized as a common and clinically important form of hypertension. Expanded screening for primary aldosteronism has revealed many individuals with suppressed renin who do not meet the diagnostic criteria for aldosterone excess, yet exhibit features consistent with sodium retention or increased mineralocorticoid activity. This review synthesizes evidence from targeted literature searches on the epidemiology, mechanisms, diagnostic challenges, and treatment of low-renin hypertension. Early studies proposed renin, in the presence of hypertension, as a marker of excess sodium retention and volume expansion, suggesting that renin could guide individualized therapy. Adoption of a renin-guided treatment approach was historically limited by assay variability and concerns regarding adverse effects from high-dose mineralocorticoid receptor antagonists. However, improvements in renin assay performance, increased accessibility and use of renin testing, and the availability of lower-dose and better-tolerated mineralocorticoid receptor antagonists have renewed interest in this strategy. Low-renin hypertension encompasses primary aldosteronism, conditions that mimic mineralocorticoid excess, and disorders of renal tubular sodium transport. Across this spectrum, patients respond more favorably to therapies targeting sodium retention: mineralocorticoid receptor antagonists, epithelial sodium channel inhibitors, or thiazide diuretics, than to agents directed primarily at vasoconstriction. Recognition of low-renin hypertension as a distinct phenotype enables mechanism-based therapy and may improve blood pressure control, reduce medication burden, and mitigate long-term cardiovascular risk.