Renal Denervation for Hypertension Management: Past, Current Evidence and Future Directions

Hypertension remains the most prevalent modifiable cardiovascular risk factor worldwide, and continues to account for substantial morbidity, mortality, and health care burden despite established pharmacologic and lifestyle-based therapies. Poor long-term adherence, therapeutic inertia, polypharmacy, and persistent implementation gaps have generated interest in device-based therapies that provide durable BP reduction, independent of daily medication use. Renal denervation (RDN) has emerged as the most extensively studied catheter-based intervention targeting the sympathetic pathways that contribute to blood pressure regulation. This review summarizes the physiological basis for RDN, including the role of efferent and afferent renal sympathetic pathways in the development and maintenance of hypertension. We review the evolution of RDN technology from first-generation radiofrequency systems to multielectrode radiofrequency, ultrasound-based, and alcohol-mediated platforms, with attention to procedural refinements and lesion patterns over time. We then examine the clinical evidence across major trials, from early open-label studies to modern sham-controlled programs, which now consistently demonstrate modest but clinically meaningful reductions in ambulatory and office BP with an acceptable safety profile in selected patients. Beyond BP lowering, renal denervation may have broader biologic effects on cardiac remodeling, neurohormonal activation, inflammation, arrhythmias, metabolic dysfunction, and cardiorenal pathways, although these data remain preliminary, without any evidence from outcome studies. Important knowledge gaps persist, particularly the absence of cardiovascular outcomes trials, variability in treatment response, and the need for improved phenotyping to identify likely responders. As technology, patient selection, and mechanistic understanding continue to advance, RDN may become an increasingly important adjunct in the management of uncontrolled hypertension.