Front Neurosci. 2026 Jul 31;20:1863953. doi: 10.3389/fnins.2026.1863953. eCollection 2026.
ABSTRACT
Chronic kidney disease (CKD) confers disproportionate high risk for cardiovascular morbidity and mortality. Hypertension remains both a driver and consequence of progressive renal dysfunction. Beyond sodium retention, volume expansion, and renin-angiotensin-aldosterone system activation, increasing evidence supports a CKD phenotype of sustained sympathetic activation coupled with impaired autonomic buffering and altered vascular responsiveness. Baroreflex sensitivity is reduced across pre-dialysis and dialysis cohorts and is linked to arterial stiffening and vascular calcification, changes that amplify blood pressure variability and central hemodynamic load. In parallel, CKD has been associated with enhanced α1-adrenergic responsiveness, suggesting that sympathetic neurovascular transduction may be altered and thereby contribute to elevated total peripheral resistance and blood pressure lability. Renal denervation (RDN) disrupts renal sympathetic nerve traffic and has re-emerged as an adjunctive therapy for selected patients with uncontrolled or resistant hypertension in contemporary international guidelines. By attenuating renal efferent signaling and interrupting afferent kidney-brain reflex pathways, RDN provides both a therapeutic option and a translational probe into the kidney's contribution to global sympathetic drive. In end-stage kidney disease, early proof-of-concept studies demonstrate feasibility and report reductions in sympathetic indices in subsets undergoing repeat physiological assessment. This review summarizes current evidence on vascular function and autonomic control of the vasculature in CKD, emphasizing kidney-brain signaling, baroreflex impairment, endothelial dysfunction, arterial stiffening, and neurovascular transduction, and examines available evidence for RDN in patients with diminished renal function. We highlight mechanistic gaps, responder phenotypes, and priorities for future research aimed at targeted neuromodulation strategies in CKD.
PMID:42602013 | PMC:PMC13472995 | DOI:10.3389/fnins.2026.1863953