Combined Aldosterone Synthase and SGLT2 Inhibition: A Recipe for Success in CKD with Uncontrolled Blood Pressure?

To evaluate the emerging role of aldosterone synthase inhibitors (ASIs) in combination with sodium-glucose cotransporter 2 (SGLT2) inhibitors for the management of uncontrolled hypertension in patients with chronic kidney disease (CKD), and to assess their potential cardiorenal benefits.

SGLT2 inhibitors confer modest blood pressure reduction alongside cardiorenal protection across diverse CKD populations. ASIs such as baxdrostat and lorundrostat demonstrate clinically meaningful reductions in systolic blood pressure, with early evidence suggesting favorable effects on albuminuria. Recent trials in CKD populations demonstrate improved blood pressure control and reductions in proteinuria, while combination therapy suggests mitigation of hyperkalemia risk through SGLT2 inhibitor-induced kaliuresis. Ongoing large-scale trials are evaluating long-term renal and cardiovascular outcomes of this combination strategy. The combination of ASIs and SGLT2 inhibitors represents a mechanistically complementary approach to targeting RAAS dysregulation, volume status, and metabolic pathways. This strategy has the potential to redefine treatment paradigms for CKD-associated uncontrolled hypertension, pending evaluation of long-term outcome benefits.