Pathophysiology of Hypertension in Chronic Kidney Disease: Role of the Sympathetic Nervous System Activation

Hypertension is a prevalent and multifactorial complication of chronic kidney disease (CKD), affecting more than 80% of patients and significantly contributing to cardiovascular morbidity and mortality. Among the numerous mechanisms involved, sympathetic nervous system (SNS) overactivation has emerged as a key pathophysiological driver. In CKD, impaired renal excretory and endocrine function leads to compensatory activation of neural and hormonal systems, including persistent SNS stimulation. Afferent renal nerve signaling, accumulation of uremic toxins, baroreceptor dysfunction, enhanced renin–angiotensin-aldosterone system activity, nitric oxide deficiency, and oxidative stress collectively contribute to chronic sympathoexcitation. This overactivity not only elevates blood pressure but also promotes structural and functional damage to the heart, vasculature, and kidneys—independent of hemodynamic effects. Therapeutic strategies targeting SNS overactivity, including pharmacological agents, device-based interventions, and lifestyle modifications, offer a promising approach to improving cardiovascular outcomes and slowing CKD progression. This chapter provides a comprehensive overview of the mechanisms, clinical consequences, and current and emerging therapeutic options related to SNS activation in the setting of CKD.