The following are key points to remember about this state-of-the-art review on renal denervation (RDN) from the International Sympathetic Nervous System Summit:

What is known about RDN-mediated blood pressure (BP) lowering:

• Mechanisms of RDN-induced BP lowering include selective inhibition of renal efferent and afferent neural signaling, as well as potential anti-inflammatory and drug interactions.
• The sham-controlled SYMPLICITY HTN-3 trial did not demonstrate superiority of RDN in reducing BP compared with a sham group at 6 months’ post-procedure. These results were attributed to patient selection, medication adherence, suboptimal procedural performance, and operator experience.
• Since then, four other adequately designed, randomized, sham-controlled trials have confirmed the BP-lowering efficacy of catheter-based RDN: the DENERHTN, SPYRAL HTN-OFF MED, RADIANCE-HTN SOLO, and SPYRAL HTN-ON MED trials. All demonstrated a clinically significant reduction (5-7 mm Hg) of ambulatory systolic BP in comparison with respective sham-control groups.

What is unknown about RDN-mediated BP lowering:

• Underlying mechanisms capable of chronically maintaining a sustained decrease in BP despite potential re-innervation are unknown. Reduced renal vascular resistance, decreased intra-renal levels of renin, changes in central autonomic nuclei, and others are possible explanations that require further exploration.
• There is evidence suggesting that inflammation of the vasculature, brain, and kidneys contributes to chronic increases in BP but there is a shortage of clinical studies directly measuring renal inflammation after RDN. Further clinical and preclinical investigations are necessary to elucidate the anti-inflammatory effect of RDN.
• Centrally acting agents like clonidine are useful in hypertension patients with a hyperactive sympathetic nervous system. The premise that patients with greater sympathetic-dependent hypertension (clonidine-sensitive) may represent a more susceptible population for RDN remains to be tested.

Conclusion:

• Sympathetic nervous system activation is a key contributor to elevated BP. Catheter-based RDN reduces BP in both treated and drug-naïve patients. Improved trial design, patient selection, and optimized procedural approaches contributed to these positive findings. Future research should focus on reducing the variability of the BP response and indications beyond hypertension. Several unsolved issues include identifying patients who will benefit most, assessing long-term durability and safety of RDN, and developing tests to better identify technical success at the time of the procedure.

Keywords: Blood Pressure, Blood Pressure Monitoring, Ambulatory, Clonidine, Denervation, Drug Interactions, Hypertension, Inflammation, Medication Adherence, Metabolic Syndrome, Patient Selection, Primary Prevention, Renin, Sympathetic Nervous System, Vascular Diseases, Vascular Resistance

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