2025 Update on resistant hypertension in CKD: where do we stand and where do we go?

Resistant hypertension is highly prevalent among individuals with chronic kidney disease (CKD) and is closely associated with accelerated decline of renal function and increased cardiovascular morbidity and mortality. Recent clinical guidelines have established clearer blood pressure (BP) targets for this population, generally recommending office BP values below 140/90 mmHg, with a more stringent target of <130/80 mmHg for patients with albuminuria, diabetes, high cardiovascular risk, or transplant. Conversely, systolic pressure <120 mmHg is not advised due to concerns regarding renal hypoperfusion and associated adverse cardiovascular outcomes. Initial treatment involves an optimized triple therapy regimen with a renin-angiotensin system blocker, a calcium channel blocker, and a diuretic, with the addition of beta-blockers in patients with cardiac comorbidities. Patients with poorly controlled BP require a fourth agent. Spironolactone remains a preferred option when the estimated glomerular filtration rate is ≥30 ml/min/1.73 m², but long-term adherence is poor. Chlorthalidone is suitable in more advanced CKD, particularly combined with loop diuretics. Centrally sympatholytic agents represent a valuable alternative. Sodium-glucose cotransporter 2 inhibitors, non-steroidal mineralocorticoid receptor antagonists, and glucagon-like peptide 1 receptor agonists have demonstrated both antihypertensive effects and clear renal and cardiovascular benefits. Dual endothelin receptor antagonist may offer an additional option in patients with resistant hypertension. Renal denervation represents another promising approach. In selected cases of atherosclerotic renovascular disease with high-grade stenosis and clinical risk features, revascularization may provide benefit. Collectively, these developments support a more individualized and evidence-based approach to managing resistant hypertension in CKD.