Aldosterone-targeted therapies: early implementation in resistant hypertension and chronic kidney disease

Abstract Treatment-resistant hypertension (TRH) often coexists with chronic kidney disease (CKD), and the presence of both conditions increases the risk of adverse cardiovascular outcomes. Patients with TRH and CKD exhibit enhanced aldosterone and mineralocorticoid receptor expression, which promote inflammation and fibrosis in cardiac and renal tissues, contributing to the development and progression of cardiorenal diseases. Both achieving optimal blood pressure (BP) control and mitigating the risk of aldosterone-related adverse events are cornerstones in the management of patients with TRH and CKD. Mineralocorticoid receptor antagonists (MRAs) are recommended for the treatment of TRH. To date, the efficacy has been investigated in populations with mostly normal renal function. However, the potential risk of hyperkalaemia limits the use of MRAs, particularly in patients with CKD. Non-steroidal MRAs and sodium glucose cotransporter-2 inhibitors have slowed renal function decline and shown cardiorenal benefits. Additionally, aldosterone synthase inhibitors may emerge as a therapeutic option for patients with TRH. Clinical trials for TRH primarily centred on assessing BP-lowering effects; however, merely lowering BP might not be a sufficient target to prevent a risk of cardiorenal disease progression. This paper presents evidence and potential benefits of aldosterone-targeted therapy in the treatment of TRH and CKD and re-consider the treatment strategies in clinical practice and trial design.