Chronic kidney disease (CKD) and high blood pressure (BP) are closely linked and, when not managed appropriately, can lead to serious outcomes such as myocardial infarction, stroke, heart failure, and progression to kidney failure. Among patients with CKD, uncontrolled hypertension (HTN) is one of the most common modifiable risk factors for cardiovascular events and CKD progression, regardless of the cause of CKD. The prevalence of HTN is 67% to as high as 92% among individuals with CKD; the majority of patients with CKD and HTN do not achieve BP targets. In a recent World Health Organization report, 62% of deaths from CKD were attributed to elevated systolic BP.
Pathological excess of aldosterone induces HTN by forcing the kidneys to excessively retain sodium and water, increasing blood volume, and lowering potassium. Beyond fluid retention, it causes HTN by increasing vascular resistance, stimulating inflammation, and promoting vascular/cardiac fibrosis and remodeling. Excessive aldosterone damages the kidneys; achieving optimal BP control and mitigating the risk of aldosterone-related adverse events are cornerstones in the management of patients with HTN and CKD.
Mineralocorticoid receptor antagonists (MRAs), which target the renin-angiotensin-aldosterone system (RAAS), do not fully inhibit the deleterious effects of aldosterone and may increase serum aldosterone concentrations. Highly selective aldosterone synthase inhibitors (ASIs) have emerged as potential alternatives to MRAs; ASIs decrease aldosterone synthesis, providing another strategy to inhibit aldosterone effects without affecting cortisol production. In this symposium, the role of aldosterone dysregulation in the pathophysiology of cardiovascular, endocrine, and renal diseases will be explained. Evidence with currently available MRAs for the treatment of uncontrolled and resistant hypertension will be interpreted. The rationale for development of highly selective ASIs will be described, and emerging data with ASIs for the treatment of hypertension discussed.
Upon completion of this activity, participants should be able to: