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Renal sympathetic denervation: applications in hypertension and beyond

Abstract

Renal afferent and efferent sympathetic nerves are involved in the regulation of blood pressure and have a pathophysiological role in hypertension. Renal sympathetic denervation is a novel therapeutic technique for the treatment of patients with resistant hypertension. Clinical trials of renal sympathetic denervation have shown significant reductions in blood pressure in these patients. Renal sympathetic denervation also reduces heart rate, which is a surrogate marker of cardiovascular risk. Conditions that are comorbid with hypertension, such as heart failure and myocardial hypertrophy, obstructive sleep apnoea, atrial fibrillation, renal dysfunction, and metabolic syndrome are closely associated with enhanced sympathetic activity. In experimental models and case–control studies, renal denervation has had beneficial effects on these conditions. Renal denervation could become a commonly used procedure to treat resistant hypertension and chronic diseases associated with enhanced sympathetic activation. Current work is focused on refining the techniques and interventional devices to provide safe and effective renal sympathetic denervation. Controlled studies in patients with mild-to-moderate, nonresistant hypertension and comorbid conditions such as heart failure, diabetes mellitus, sleep apnoea, and arrhythmias are needed to investigate the capability of renal sympathetic denervation to improve cardiovascular outcomes.

Key Points

  • Sympathetic activity has an important role in the pathophysiology of diseases such as systemic hypertension, arrhythmias, metabolic syndrome, and heart failure

  • Signalling between the kidneys and the central sympathetic nervous system is bidirectional and occurs through the renal afferent and efferent nerves

  • Renal sympathetic denervation reduces both renal and central sympathetic activity, as well as blood pressure, in patients with resistant hypertension

  • Clinical and experimental data suggest that modulation of sympathetic activity might also reduce heart rhythm disturbances such as atrial fibrillation and ventricular arrhythmias

  • Reduced left ventricular hypertrophy and improved diastolic function have also been observed in patients after renal denervation, indicating that this technique could be used to treat diastolic heart failure

  • Whether renal denervation can improve other diseases characterized by elevated sympathetic activity, including hyperinsulinaemia, diabetes mellitus, metabolic syndrome, and obstructive sleep apnoea, is currently being investigated

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Figure 1: Pathophysiological interactions between the brain and kidney increase total body sympathetic activity.
Figure 2: Design and main results of the Symplicity-HTN2 study.
Figure 3: The technique of renal denervation.
Figure 4: Suggested timelines for clinical observations before and after interventional renal sympathetic denervation.
Figure 5: Effect of renal denervation on heart rate and SBP.
Figure 6: Effect of RDN on inducibility of AF in a pig model of obstructive sleep apnoea.
Figure 7: Effect of RDN on renal resistive indices, renal function, and UAE.
Figure 8: Changes in metabolic parameters at 1 month and 3 months after RDN versus a medically treated control group.

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Acknowledgements

M. Böhm's and C. Ukena's research is supported by the Deutsche Forschungsgemeinschaft (DFG, KFO 196). D. Linz's and F. Mahfoud's research is supported by the Deutsche Hochdruckliga. All the authors' research is supported by the German Cardiac Society.

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All the authors researched the data for the article, provided substantial contributions to discussions of its content, and undertook review and/or editing of the manuscript before submission. M. Böhm wrote the article.

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Correspondence to Michael Böhm.

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M. Böhm and F. Mahfoud declare that they have received grant or research support from Cordis, Medtronic Ardian, and St. Jude Medical. All authors declare that their institution has received scientific grants from Bayer, Boehringer Ingelheim, Medtronic, Pfizer, Servier, and St. Jude Medical.

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Böhm, M., Linz, D., Urban, D. et al. Renal sympathetic denervation: applications in hypertension and beyond. Nat Rev Cardiol 10, 465–476 (2013). https://doi.org/10.1038/nrcardio.2013.89

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