Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Selective renal denervation guided by renal nerve stimulation: mapping renal nerves for unmet clinical needs

Subjects

Abstract

Renal denervation (RDN) is a well-known innovative therapy for hypertension. However, the effects of global RDN on blood pressure (BP) lowering are quite variable. Insufficient and futile denervation is considered a major factor contributing to the variable results. Mapping renal nerves by renal nerve stimulation (RNS) is the most promising technique to improve the efficacy of RDN. We summarize the clinical and experimental data available regarding RNS-guided RDN and explain the roles of renal efferent nerves, afferent nerves and vagal nerves in BP changes. We further identify five different BP response patterns to RNS and provide an explanation of the underlying neuroanatomical basis.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Fudim M, Sobotka AA, Yin YH, Wang JW, Levin H, Esler M, et al. Selective vs. global renal denervation: a case for less is more. Curr Hypertens Rep. 2018;20:37.

    Article  Google Scholar 

  2. de Jong MR, Hoogerwaard AF, Adiyaman A, Smit JJJ, Heeg JE, van Hasselt B, et al. Renal nerve stimulation identifies aorticorenal innervation and prevents inadvertent ablation of vagal nerves during renal denervation. Blood Pressure. 2018:27:271–9.

  3. Krum H, Schlaich M, Whitbourn R, Sobotka PA, Sadowski J, Bartus K, et al. Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study. Lancet 2009;373:1275–81.

    Article  Google Scholar 

  4. Esler MD, Krum H, Sobotka PA, Schlaich MP, Schmieder RE, Bohm M. Renal sympathetic denervation in patients with treatment-resistant hypertension (the symplicity htn-2 trial): a randomised controlled trial. Lancet 2010;376:1903–9.

    Article  Google Scholar 

  5. Esler MD, Krum H, Schlaich M, Schmieder RE, Bohm M, Sobotka PA. Renal sympathetic denervation for treatment of drug-resistant hypertension: one-year results from the symplicity htn-2 randomized, controlled trial. Circulation 2012;126:2976–82.

    Article  CAS  Google Scholar 

  6. Bakris GL, Townsend RR, Liu M, Cohen SA, D’Agostino R, Flack JM, et al. Impact of renal denervation on 24-hour ambulatory blood pressure: results from symplicity htn-3. J Am Coll Cardiol. 2014;64:1071–8.

    Article  Google Scholar 

  7. Azizi M, Sapoval M, Gosse P, Monge M, Bobrie G, Delsart P, et al. Optimum and stepped care standardised antihypertensive treatment with or without renal denervation for resistant hypertension (denerhtn): a multicentre, open-label, randomised controlled trial. Lancet 2015;385:1957–65.

    Article  Google Scholar 

  8. Bohm M, Mahfoud F, Ukena C, Hoppe UC, Narkiewicz K, Negoita M, et al. First report of the global symplicity registry on the effect of renal artery denervation in patients with uncontrolled hypertension. Hypertension. 2015;65:766–74.

    Article  Google Scholar 

  9. Volz S, Spaak J, Elf J, Jagren C, Lundin C, Stenborg A, et al. Renal sympathetic denervation in sweden: a report from the swedish registry for renal denervation. J Hypertens. 2018;36:151–8.

    Article  Google Scholar 

  10. Tsioufis C, Dimitriadis K, Papademetriou V, Tousoulis D. Spyral htn-off med study: renal denervation in the spiral orbits of current results and future studies. Hell J Cardiol: HJC=Hell Kardiol Epitheorese. 2017;58:320–1.

    Article  Google Scholar 

  11. Azizi M, Schmieder RE, Mahfoud F, Weber MA, Daemen J, Davies J, et al. Endovascular ultrasound renal denervation to treat hypertension (radiance-htn solo): A multicentre, international, single-blind, randomised, sham-controlled trial. Lancet. 2018;391:2335–45.

  12. Kandzari DE, Bohm M, Mahfoud F, Townsend RR, Weber MA, Pocock S, et al. Effect of renal denervation on blood pressure in the presence of antihypertensive drugs: 6-month efficacy and safety results from the spyral htn-on med proof-of-concept randomised trial. Lancet. 2018;391:P2346–55.

  13. Kandzari DE, Bhatt DL, Brar S, Devireddy CM, Esler M, Fahy M, et al. Predictors of blood pressure response in the symplicity htn-3 trial. Eur Heart J. 2015;36:219–27.

    Article  Google Scholar 

  14. Prochnau D, Heymel S, Otto S, Figulla HR, Surber R. Renal denervation with cryoenergy as second-line option is effective in the treatment of resistant hypertension in non-responders to radiofrequency ablation. EuroIntervention. 2014;10:640–5.

    Article  Google Scholar 

  15. Kaiser L, Beister T, Wiese A, von Wedel J, Meincke F, Kreidel F, et al. Results of the alster bp real-world registry on renal denervation employing the symplicity system. EuroIntervention. 2014;10:157–65.

    Article  Google Scholar 

  16. Fengler K, Rommel KP, Blazek S, Besler C, Hartung P, von Roeder M, et al. A three-arm randomized trial of different renal denervation devices and techniques in patients with resistant hypertension (radiosound-htn). Circulation 2019;139:590–600.

    Article  Google Scholar 

  17. Krum H, Schlaich MP, Sobotka PA, Bohm M, Mahfoud F, Rocha-Singh K, et al. Percutaneous renal denervation in patients with treatment-resistant hypertension: final 3-year report of the symplicity htn-1 study. Lancet 2014;383:622–9.

    Article  Google Scholar 

  18. Townsend RR, Mahfoud F, Kandzari DE, Kario K, Pocock S, Weber MA, et al. Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (spyral htn-off med): a randomised, sham-controlled, proof-of-concept trial. Lancet 2017;390:2160–70.

    Article  Google Scholar 

  19. Dobrowolski LC, Eeftinck Schattenkerk DW, Krediet CTP, Van Brussel PM, Vogt L, Bemelman FJ, et al. Renal sympathetic nerve activity after catheter-based renal denervation. EJNMMI Res. 2018;8:8.

    Article  Google Scholar 

  20. Pokushalov E, Romanov A, Corbucci G, Artyomenko S, Baranova V, Turov A, et al. A randomized comparison of pulmonary vein isolation with versus without concomitant renal artery denervation in patients with refractory symptomatic atrial fibrillation and resistant hypertension. J Am Coll Cardiol. 2012;60:1163–70.

    Article  Google Scholar 

  21. Chinushi M, Izumi D, Iijima K, Suzuki K, Furushima H, Saitoh O, et al. Blood pressure and autonomic responses to electrical stimulation of the renal arterial nerves before and after ablation of the renal artery. Hypertension 2013;61:450–6.

    Article  CAS  Google Scholar 

  22. Chinushi M, Suzuki K, Saitoh O, Furushima H, Iijima K, Izumi D, et al. Electrical stimulation-based evaluation for functional modification of renal autonomic nerve activities induced by catheter ablation. Heart Rhythm 2016;13:1707–15.

    Article  Google Scholar 

  23. Lu J, Wang Z, Zhou T, Chen S, Chen W, Du H, et al. Selective proximal renal denervation guided by autonomic responses evoked via high-frequency stimulation in a preclinical canine model. Circ Cardiovasc Interv. 2015;8.

  24. Gal P, de Jong MR, Smit JJ, Adiyaman A, Staessen JA, Elvan A. Blood pressure response to renal nerve stimulation in patients undergoing renal denervation: a feasibility study. J Hum Hypertens. 2015;29:292–5.

    Article  CAS  Google Scholar 

  25. de Jong MR, Adiyaman A, Gal P, Smit JJ, Delnoy PP, Heeg JE, et al. Renal nerve stimulation-induced blood pressure changes predict ambulatory blood pressure response after renal denervation. Hypertension 2016;68:707–14.

    Article  Google Scholar 

  26. Xu Y, Xiao P, Fan J, Chen W, Du H, Ling Z, et al. Blood pressure elevation response to radiofrequency energy delivery: one novel predictive marker to long-term success of renal denervation. J Hypertens. 2018;36:2460–70.

    Article  CAS  Google Scholar 

  27. Barber-Chamoux N, Esler MD. Predictive factors for successful renal denervation: should we use them in clinical trials? Eur J Clin Investig. 2017;47:860–7.

    Article  Google Scholar 

  28. Mahfoud F, Schmieder RE, Azizi M, Pathak A, Sievert H, Tsioufis C, et al. Proceedings from the 2nd european clinical consensus conference for device-based therapies for hypertension: state of the art and considerations for the future. Eur Heart J. 2017;38:3272–81.

    Article  CAS  Google Scholar 

  29. Mompeo B, Maranillo E, Garcia-Touchard A, Larkin T, Sanudo J. The gross anatomy of the renal sympathetic nerves revisited. Clin Anat. 2016;29:660–4.

    Article  Google Scholar 

  30. Fujisawa Y, Nagai Y, Lei B, Nakano D, Fukui T, Hitomi H, et al. Roles of central renin-angiotensin system and afferent renal nerve in the control of systemic hemodynamics in rats. Hypertens Res: Off J Jpn Soc Hypertens. 2011;34:1228–32.

    Article  CAS  Google Scholar 

  31. Sakakura K, Ladich E, Cheng Q, Otsuka F, Yahagi K, Fowler DR, et al. Anatomic assessment of sympathetic peri-arterial renal nerves in man. J Am Coll Cardiol. 2014;64:635–43.

    Article  Google Scholar 

  32. van Amsterdam WA, Blankestijn PJ, Goldschmeding R, Bleys RL. The morphological substrate for renal denervation: nerve distribution patterns and parasympathetic nerves. A post-mortem histological study. Ann Anat. 2016;204:71–79.

    Article  Google Scholar 

  33. Henegar JR, Zhang Y, Hata C, Narciso I, Hall ME, Hall JE. Catheter-based radiofrequency renal denervation: location effects on renal norepinephrine. Am J Hypertens. 2015;28:909–14.

    Article  CAS  Google Scholar 

  34. Murai H, Okuyama Y, Sakata Y, Kaneko S, Hamaoka T, Okabe Y, et al. Different responses of arterial blood pressure to electrical stimulation of the renal artery in patients with resistant hypertension. Int J Cardiol. 2015;190:296–8.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yuehui Yin.

Ethics declarations

Conflict of interest

The authors declare no conflicts of interest. YHY is a consultant to SyMap Medical Ltd. JW is a cofounder of SyMap Medical Ltd.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tan, K., Lai, Y., Chen, W. et al. Selective renal denervation guided by renal nerve stimulation: mapping renal nerves for unmet clinical needs. J Hum Hypertens 33, 716–724 (2019). https://doi.org/10.1038/s41371-019-0244-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41371-019-0244-5

This article is cited by

Search

Quick links