Current Cardiology Reports

, Volume 14, Issue 5, pp 619–625 | Cite as

Renal Denervation Therapies for Refractory Hypertension

Interventional Cardiology (DJ Moliterno, Section Editor)


The treatment of severe hypertension by the surgical obliteration of the renal sympathetic nerves was proposed almost 80 years ago. This approach, although highly effective in reducing blood pressure was associated with a significant amount of side effects and it was rapidly replaced by better tolerated medical therapy. The rapid progress in catheter based technologies occurring within the last 20 years facilitated the development of the first radio frequency renal artery denervation catheter. At the present time, several small trials have demonstrated the safety and efficacy of this approach among patients with refractory hypertension. Besides its effect on reducing blood pressure, other pleiotropic effects (ie, improving glycemia in diabetic patients) have been proposed. In this review, we discuss the anatomical and physiological rationale for this therapy, provide an update on the latest clinical data available and describe additional emerging technologies in this field.


Renal denervation Sympathetic Activation Hypertension Blood pressure Cardiovascular Renal nerve ablation Glucose metabolism Left ventricular hypertrophy Novel denervation therapies Refractory hypertension 



Conflicts of interest: J.F. Granada: none; P.P. Buszman: has received grant support from Medtronic, Warsaw, Poland.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Ezzati M, Lopez AD, Rodgers A, Vander Hoorn S, Murray CJ. Selected major risk factors and global and regional burden of disease. Lancet. 2002;360:1347–60.PubMedCrossRefGoogle Scholar
  2. 2.
    Law M, Wald N, Morris J. Lowering blood pressure to prevent myocardial infarction and stroke: a new preventive strategy. Health Technol Assess. 2003;7:1–94.PubMedGoogle Scholar
  3. 3.
    Mancia G, De Backer G, Dominiczak A, et al. 2007 ESH-ESC Practice Guidelines for the Management of Arterial Hypertension: ESH-ESC Task Force on the management of arterial hypertension. J Hypertens. 2007;25:1751–62.PubMedCrossRefGoogle Scholar
  4. 4.
    Mazzaglia G, Ambrosioni E, Alacqua M, et al. Adherence to antihypertensive medications and cardiovascular morbidity among newly diagnosed hypertensive patients. Circulation. 2009;120:1598–605.PubMedCrossRefGoogle Scholar
  5. 5.
    Burke TA, Sturkenboom MC, Lu SE, Wentworth CE, Lin Y, Rhoads GG. Discontinuation of antihypertensive drugs among newly diagnosed hypertensive patients in UK general practice. J Hypertens. 2006;24:1193–200.PubMedCrossRefGoogle Scholar
  6. 6.
    Calhoun DA, Jones D, Textor S, et al. Resistant hypertension: diagnosis, evaluation, and treatment: a scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Circulation. 2008;117:e510–26.PubMedCrossRefGoogle Scholar
  7. 7.
    Grimson KS. Total thoracic and partial to total lumbar sympathectomy and celiac ganglionectomy in the treatment of hypertension. Ann Surg. 1941;114:753–75.PubMedGoogle Scholar
  8. 8.
    Peet MWW, Braden S. The surgical treatment of hypertension: results in 350 consecutive cases treated by bilateral supradiaphragmatic splanchnicectomy and lower dorsal sympathetic gangliectomy. JAMA. 1940;115:1875–85.CrossRefGoogle Scholar
  9. 9.
    Perry CB. Malignant Hypertension cured by unilateral nephrectomy. Br Heart J. 1945;7:139–42.PubMedCrossRefGoogle Scholar
  10. 10.
    Lahuerta J, Bowsher D, Lipton S, Buxton PH. Percutaneous cervical cordotomy: a review of 181 operations on 146 patients with a study on the location of "pain fibers" in the C-2 spinal cord segment of 29 cases. J Neurosurg. 1994;80:975–85.PubMedCrossRefGoogle Scholar
  11. 11.
    Cohen SL. Hypertension in renal transplant recipients: role of bilateral nephrectomy. Br Med J. 1973;3:78–81.PubMedCrossRefGoogle Scholar
  12. 12.
    Huysmans FT, van Heusden FH, Wetzels JF, Hoitsma AJ, Koene RA. Antihypertensive effect of beta blockade in renal transplant recipients with or without host kidneys. Transplantation. 1988;46:234–7.PubMedCrossRefGoogle Scholar
  13. 13.
    Aperia A, Ibarra F, Svensson LB, Klee C, Greengard P. Calcineurin mediates alpha-adrenergic stimulation of Na+, K(+)-ATPase activity in renal tubule cells. Proc Natl Acad Sci U S A. 1992;89:7394–7.PubMedCrossRefGoogle Scholar
  14. 14.
    Skott O, Jensen BL. Cellular and intrarenal control of renin secretion. Clin Sci (Lond). 1993;84:1–10.Google Scholar
  15. 15.
    Ye S, Zhong H, Yanamadala V, Campese VM. Renal injury caused by intrarenal injection of phenol increases afferent and efferent renal sympathetic nerve activity. Am J Hypertens 2002;15:717–24.Google Scholar
  16. 16.
    Atherton DS, Deep NL, Mendelsohn FO. Micro-anatomy of the renal sympathetic nervous system: a human postmortem histologic study. Clin Anat. 2012;25:628–33.PubMedCrossRefGoogle Scholar
  17. 17.
    •• Krum H, Schlaich M, Whitbourn R, et al. Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study. Lancet. 2009;373:1275–81. This is the first proof-of-concept single arm study that proved safety and efficacy of catheter based renal devervation.PubMedCrossRefGoogle Scholar
  18. 18.
    Sobotka P. Long-term follow-up of catheter-based renal sympathetic denervation for resistant hypertension confirms durable blood pressure reduction. Proceedings of the American College of Cardiology Scientific Session; March 25, 2012; Chicago, IL. 2012.Google Scholar
  19. 19.
    Symplicity HTN-1 Investigators. Catheter-based renal sympathetic denervation for resistant hypertension: durability of blood pressure reduction out to 24 months. Hypertension 2011;57:911–7.Google Scholar
  20. 20.
    •• Schlaich MP, Sobotka PA, Krum H, Lambert E, Esler MD. Renal sympathetic-nerve ablation for uncontrolled hypertension. N Engl J Med. 2009;361:932–4. This is the first randomized clinical trial that showed efficacy of renal denervation therapy when compared with standard medical therapy for resistant hypertension.PubMedCrossRefGoogle Scholar
  21. 21.
    Esler MD E. Renal sympathetic denervation for treatment of resistant hypertension: One-year results from the Symplicity HTN-2 randomized controlled trial. Proceedings of the American College of Cardiology Scientific Session; March 25, 2012; Chicago, IL. 2012.Google Scholar
  22. 22.
    Kandzari DE, Bhatt DL, Sobotka PA, et al. Catheter-based renal denevation for resistant hypertension: rationale and design of the SYMPLICITY HTN-3 trial. Clin Cardiol.Google Scholar
  23. 23.
    Prochnau D, Lucas N, Kuehnert H, Figulla HR, Surber R. Catheter-based renal denervation for drug-resistant hypertension by using a standard electrophysiology catheter. EuroIntervention 2012;7:1077–80.Google Scholar
  24. 24.
    Ukena C, Mahfoud F, Kindermann I, et al. Cardiorespiratory response to exercise after renal sympathetic denervation in patients with resistant hypertension. J Am Coll Cardiol. 2011;58:1176–82.PubMedCrossRefGoogle Scholar
  25. 25.
    • Brandt MC, Mahfoud F, Reda S, et al. Renal sympathetic denervation reduces left ventricular hypertrophy and improves cardiac function in patients with resistant hypertension. J Am Coll Cardiol. 2012;59:901–9. In this study for the first time a pleiotropic effect (reduction of LV hypertropy) after renal denervation has been reported.PubMedCrossRefGoogle Scholar
  26. 26.
    Mahfoud F, Schlaich M, Kindermann I, et al. Effect of renal sympathetic denervation on glucose metabolism in patients with resistant hypertension: a pilot study. Circulation. 2011;123:1940–6.PubMedCrossRefGoogle Scholar
  27. 27.
    Witkowski A, Prejbisz A, Florczak E, et al. Effects of renal sympathetic denervation on blood pressure, sleep apnea course, and glycemic control in patients with resistant hypertension and sleep apnea. Hypertension. 2011;58:559–65.PubMedCrossRefGoogle Scholar
  28. 28.
    ACCAD M. Single-step renal denervation with the oneshot! Ablation system. EuroPCR; Paris. 2012. Europa Organisation.Google Scholar
  29. 29.
    Hoppe UC. Clinical experience with Vessix Vascular renal denervation balloon catheter. EuroPCR; Paris. 2012.Google Scholar
  30. 30.
    Worthley SG. The St Jude renal denervation system technology and clinical review. EuroPCR; Paris. 2012. Europa Organisation.Google Scholar
  31. 31.
    Gertner M. Non-invasive renal nerve inhibition for treating hypertension. EuroPCR; Paris. 2012. Europa Organisation.Google Scholar
  32. 32.
    Bausback Y. Cardiosonic TIVUSTM Technology: an intra-vascular ultrasonic catheter for targeted renal denervation. EuroPCR; Paris. 2012. Europa Organisation. Europa Organisation.Google Scholar
  33. 33.
    Waksman R. Radiation therapy to the sympathetic trunk: rational and preclinical results. EuroPCR; Paris. 2012. Europa Organisation.Google Scholar
  34. 34.
    Stefanadis C, Toutouzas K, Synetos A, et al. Chemical denervation of the renal artery by vincristine in swine. A new catheter based technique. Int J Cardiol. 2012. doi: 10.1016/j.ijcard.2012.01.002.
  35. 35.
    Owens CD, Gasper WJ, Rousselle S. Peri-adventitial renal artery delivery of guanethidine monosulfate attenuates renal nerve function: preclinical experience and implication for resistant hypertension. J Am Coll Cardiol. 2011;58:B120.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Skirball Center for Cardiovascular Research for Cardiovascular Research FoundationOrangeburgUSA
  2. 2.American Heart of PolandCenter for Cardiovascular Research and DevelopmentKatowicePoland

Personalised recommendations