Hypertension and chronic kidney disease frequently coexist and mutually accelerate cardiovascular and renal injury. This narrative review prioritizes direct human autonomic phenotyping (Level 1: microneurography, HRV/BRS), human vascular correlates (Level 2: PWV, FMD), and complementary preclinical evidence (Level 3) to elucidate autonomic-vascular mechanisms. Autonomic imbalance, characterized by sympathetic overactivity and reduced parasympathetic restraint, represents a key interface between neural control and vascular pathology in this setting. This narrative review synthesizes experimental and clinical evidence on how the autonomic nervous system shapes vascular function in hypertension and CKD. We outline physiological autonomic control of vascular tone (baroreflex pathways, central networks, brain–kidney communication), characteristic autonomic alterations in hypertension (elevated MSNA, impaired HRV/BRS), and their vascular consequences (endothelial dysfunction, arterial stiffness). We emphasize CKD-specific autonomic drivers (renal afferents, uremic toxins, inflammation) and their translation to exaggerated vascular injury and adverse BP phenotypes. Finally, we discuss pharmacological/device-based strategies targeting autonomic–vascular pathways, highlighting opportunities for neuromodulation, biomarker-guided risk stratification, and individualized treatment. By integrating multidisciplinary evidence, this review frames CKD hypertension as amplified autonomic–vascular injury and positions the autonomic nervous system as a promising therapeutic target.

