Aldosterone Dysregulation in Hypertensive Crises: A New Endocrine–renal Risk Model

Objective: To determine whether aldosterone dysregulation within the renin angiotensin aldosterone system (RAAS) identifies a distinct high risk phenotype in hypertensive crises and to explore its interaction with renal function and target organ damage on clinical severity. Design and method: Patients admitted to the Coronary Care Unit of Hospital Espanol de Mendoza between January 1, 2024 and October 31, 2025, with a diagnosis of hypertensive crisis requiring hospitalization were prospectively included. Inclusion criteria were age greater than or equal to 18 years and severe hypertension defined as systolic blood pressure greater than or equal to 180 mmHg and/or diastolic blood pressure greater than or equal to 120 mmHg, with or without evidence of target organ damage. Exclusion criteria were secondary hypertension or any identifiable endocrine cause. Demographic, clinical, and biochemical variables were recorded, including plasma aldosterone, renin, potassium, creatinine, and lipid metabolic parameters. Aldosterone dysregulation (ALDODYSREG) was defined as aldosterone above the 75th percentile, renin below the 25th percentile, or potassium lower than 3. 5 mmol/L, representing a dissociation within the RAAS. Patients were categorized into four combined phenotypes integrating aldosterone dysregulation and organ damage. The primary outcome was length of hospitalization in calendar days. Between group differences were analyzed using Kruskal Wallis and Dunn's post hoc tests, and a linear model assessed the modifying effect of creatinine. Results: Median hospitalization increased across phenotypes 0 to 3 (3, 5, 6, and 8 days respectively, p<0. 001). The interaction between aldosterone dysregulation and creatinine was significant (beta 1. 31, 95 percent CI 0. 47 to 2. 15, p=0. 002), confirming a synergistic endocrine renal effect. Increasing quartiles of aldosterone and aldosterone renin ratio correlated with longer hospitalization (p for trend <0. 001). Cluster analysis identified hyporeninemic hyperaldosteronic and elderly renal dysfunction phenotypes as the most severe profiles. Conclusions: Aldosterone dysregulation defines a high risk endocrine renal phenotype in hypertensive crises, characterized by longer hospitalization and greater target organ damage. These findings support an endocrine renal risk model and the potential role of mineralocorticoid targeted therapies for precision management of severe hypertension.