Beyond the Anatomy of Renal Nerves: Functional Diversity of Renal Nerves

Excerpt

Renal denervation (RDN) has been considered a very promising therapeutic option for patients with resistant hypertension (HTN) and uncontrolled hypertension. Early clinical studies demonstrated remarkable reductions in blood pressure among patients with elevated baseline systolic BP despite taking three or more antihypertensive medications [1, 2]. However, the first large sham-controlled clinical trial evaluating RDN did not demonstrate reduction in office systolic BP at 6 months [3], and another study failed to demonstrate consistent reductions in 24-h ambulatory BP at 3 months [4]. The most recent sham-controlled trial revealed significant heterogeneity of BP reduction at 3 months with unselected RDN in the absence of antihypertensive medications (SPYRAL HTN OFF-MED trial) [5]. Yet, unselected RDN with utilization of antihypertensive medications yielded varying results at 3-month and 6-month follow-up (SPYRAL HTN ON-MED) [6]. Both studies further confirmed the efficacy and safety of RDN but the amplitude of office systolic BP reduction was moderate: around 10 mmHg because 20–30% patients were no-responders whose BP was not decreased or even increased after RDN. This may counteract BP-lowering effects achieved by RDN. Comparisons of different RDN methods have also yielded varying results. Among patients with resistant hypertension, endovascular ultrasound–based RDN demonstrated superiority to radiofrequency ablation of the main renal arteries only, whereas a combined approach of radiofrequency ablation of the main arteries, accessories, and side branches proved no difference (RADIOSOUND-HTN) [7]. It has been demonstrated that an approximately 30% non-responder rate was consistently observed among various energies-based RDN [8]. These cumulative findings have motivated the scientific community and medical device industry to re-evaluate the subtle implications of renal vascular anatomy, physiological responses to renal nerve stimulations, and differences in device and trial design. This recognition that RDN can produce heterogeneous afferent sympathetic effects has both changed therapeutic goals and revitalized the potential of therapeutic RDN to provide significant clinical benefits by closely examining the renal neurovascular interactions. …