Aldosterone synthase inhibitors for uncontrolled and resistant hypertension in CKD: an assessment from bench to bedside

Hypertension is highly prevalent in chronic kidney disease (CKD) and frequently remains uncontrolled despite high treatment rates; resistant hypertension occurs in up to 40% of CKD patients and markedly increases renal and cardiovascular risk. Aldosterone dysregulation plays a central role in this setting, contributing not only to sodium retention and volume expansion but also to inflammation, fibrosis and target-organ damage in the kidney, heart and vasculature. While spironolactone is recommended as the preferable fourth agent in resistant hypertension, its use in advanced CKD is limited by scarce data, and high rates of hyperkalemia and declining kidney function. Aldosterone synthase inhibitors (ASIs) are an emerging therapeutic class that directly suppress aldosterone production. Recent Phase 2 and 3 randomized controlled trials demonstrate that next-generation, selective ASIs produce clinically meaningful reductions in office and ambulatory blood pressure (BP) in patients with uncontrolled and resistant hypertension, with an acceptable safety profile. Early Phase 2 trials have also shown that ASIs are effective in lowering office BP levels in CKD with accompanying substantial reductions in albuminuria. This review examines the potential clinical benefits of aldosterone synthesis targeted therapy in the management of uncontrolled and resistant hypertension in CKD.