Low-renin hypertension is a common but under-recognised form of hypertension characterised by low circulating renin levels and variable degrees of mineralocorticoid receptor activation. Although often considered synonymous with primary aldosteronism, it encompasses a broader spectrum of disorders with important implications for diagnosis, cardiovascular risk, and treatment.

Studies suggest that low-renin hypertension is prevalent in both community and specialist settings and is likely to be identified more frequently with the increasing use of renin and aldosterone measurements for primary aldosteronism screening. Diagnosis remains challenging because of heterogeneous definitions and limitations of current screening approaches. Emerging techniques, including steroid profiling, are providing new insights into the pathophysiology of low-renin hypertension and may support more precise, mechanism-based classification.

This presentation will review contemporary concepts in low-renin hypertension, including the growing recognition of a continuum that extends beyond classical primary aldosteronism. Evidence regarding its prevalence, clinical characteristics, cardiovascular significance, and practical challenges in diagnosis and management will be discussed. By integrating advances in epidemiology, pathophysiology, steroid profiling, and therapeutics, this presentation will outline a contemporary framework for understanding low-renin hypertension and its implications for personalised hypertension care.

The actions of the mineralocorticoid, aldosterone, are mediated by the mineralocorticoid receptor (MR), a member of the nuclear receptor superfamily of ligand-dependent transcription factors. The MR appears in vertebrate evolution before aldosterone and indeed responds to two physiological ligands, aldosterone and cortisol (and also perhaps a third, progesterone). In epithelial tissues, aldosterone selectivity is determined by 11β-hydroxysteroid dehydrogenase type II. In other tissues cortisol is the primary ligand with multiple roles in cardiovascular function, immune cell signalling, neuronal function and adipocyte differentiation. These actions, beyond simply sodium homeostasis and hypertension, contribute to the disproportionate morbidity associated with hyperaldosteronism and the benefit observed more broadly in cardiovascular disease with the use of MR antagonists. This diversity of responses at the MR, including ligand- and tissue-specificity, is achieved through critical interactions involved in MR-mediated signal transduction. Signalling is initiated by ligand-binding which confers a ligand-specific, agonist or antagonist, conformation upon the receptor. This conformation then determines subsequent interactions within the receptor, with other transcription factors independent of DNA-binding, and with coregulatory molecules. Studies of MR evolution, targeted mutagenesis in transgenic mice and receptor chimeras have enabled dissection of the determinants of these conformational changes. Identification of the structural basis of antagonism at the MR, and of ligand-specific interactions of the MR, may provide the basis for the development of novel ligands with the ability to modulate the MR response and provide tissue specificity.

Aldosterone plays a central role in hypertension, cardiovascular disease, and chronic kidney disease (CKD) through effects that extend beyond blood pressure elevation, including inflammation, fibrosis, and adverse cardiorenal remodeling. Growing evidence has positioned aldosterone-targeted therapies as an important component of contemporary cardiorenal risk reduction strategies.
This presentation will review the evolving evidence supporting mineralocorticoid receptor antagonism and aldosterone synthase inhibition in patients at high cardiovascular and kidney risk. Key data from landmark trials of finerenone in CKD have demonstrated meaningful reductions in kidney disease progression and cardiovascular events, establishing non-steroidal mineralocorticoid receptor antagonism as a foundational therapy in cardiorenal medicine. Emerging evidence for aldosterone synthase inhibitors, including their effects on blood pressure reduction and aldosterone suppression, will also be examined, alongside their potential role in resistant hypertension and broader cardiorenal protection.
The session will explore the biological rationale for targeting aldosterone, compare currently available and investigational therapeutic approaches, and discuss practical considerations for implementation in clinical practice. Together, these advances signal a new era in hypertension management, where aldosterone-directed therapies may deliver benefits extending well beyond blood pressure control to improve long-term kidney and cardiovascular outcomes.