New pharmacologic and interventional horizons in hypertension and nondialysis chronic kidney disease: bridging innovation and clinical translation.

Abstract

Hypertension is highly prevalent among patients with chronic kidney disease (CKD), where it functions both as a cause and a consequence of disease progression. Renin-angiotensin-aldosterone system inhibitors remain foundational for nephroprotection, with calcium channel blockers, thiazide diuretics and mineralocorticoid receptor antagonists (MRAs) commonly added to improve blood pressure (BP) control. However, the limited efficacy of thiazides at low estimated glomerular filtration rate and the increased risk of hyperkalemia with MRAs, together with polypharmacy, and suboptimal adherence, further complicate BP management in advanced CKD. Emerging pharmacologic strategies - including nonsteroidal MRAs, aldosterone synthase inhibitors, and RNA-based therapies - offer mechanism-oriented approaches to optimize cardiorenal outcomes. Complementary interventional strategies, such as renal denervation and low-intensity shockwave intravascular lithotripsy, are being evaluated for their potential to improve BP control, while therapies targeting inflammatory pathways, enhancing natriuretic peptide signaling, or leveraging vaccine-based mechanisms may address residual risk and adherence challenges. In this review, we provide a comprehensive overview of emerging pharmacologic and interventional approaches for BP management in nondialysis CKD, highlighting mechanism-driven innovations and their potential clinical translation.