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Renal denervation therapy for resistant hypertension: a clinical update

Journal of Human Hypertension volume 28, pages 699–704 (2014)Cite this article

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Abstract

Severe hypertension (systolic blood pressure (BP) ⩾160 mm Hg) resistant to treatment with multiple antihypertensive medications, poses a serious challenge to therapeutic treatment. Catheter-based renal denervation (RDN) is being increasingly proposed and researched as a safe and effective method of treating this condition. This article evaluates the existing evidence on the effects of RDN on BP reduction and other conditions with increased sympathetic tone. Findings indicate that RDN is a safe and effective treatment for severe hypertension. Moreover, the antihypertensive response to RDN is sustained for up to 3 years of follow-up. RDN decreases office BP more than ambulatory BP, which may be explained by the white-coat effect that causes an increase in office BP. Findings indicate that although reinnervation may occur following RDN, it does not appear to attenuate or reverse the BP response over 24–36 months. There is also evidence that patients with milder forms of hypertension may benefit from RDN. Furthermore, there is emerging evidence that RDN may have a role in the treatment of heart failure, obstructive sleep apnea, insulin resistance, atrial fibrillation and hypertension associated with end-stage renal disease. Taking into account that resistant hypertension and other diseases associated with elevated sympathetic tone are associated with significant morbidity and mortality rates, RDN therapy may be expected to have a significant impact on public health.

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References

  1. Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J . Global burden of hypertension: analysis of worldwide data. Lancet 2005; 365: 217–223.

    Article  Google Scholar 

  2. Calhoun DA, Jones D, Textor S, Goff DC, Murphy TP, Toto RD 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–e526.

    Article  Google Scholar 

  3. Epstein M, Calhoun DA . Aldosterone blockers (mineralocorticoid receptor antagonism) and potassium-sparing diuretics. J Clin Hypertens (Greenwich) 2011; 13: 644–648.

    Article  CAS  Google Scholar 

  4. Pimenta E, Calhoun DA . Resistant hypertension: incidence, prevalence, and prognosis. Circulation 2012; 125: 1594–1596.

    Article  Google Scholar 

  5. Muxfeldt ES, de Souza F, Salles GF . Resistant hypertension: a practical clinical approach. J Hum Hypertens 2013; 27: 657–662.

    Article  CAS  Google Scholar 

  6. 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: 1275–1281.

    Article  Google Scholar 

  7. Mahfoud F, Lüscher TF, Andersson B, Baumgartner I, Cifkova R, Dimario C et al. Expert consensus document from the European Society of Cardiology on catheter-based renal denervation. Eur Heart J 2013; 34: 2149–2157.

    Article  Google Scholar 

  8. Hering D, Lambert EA, Marusic P, Ika-Sari C, Walton AS, Krum H et al. Substantial reduction in single sympatheticnerve firing after renal denervation in patients with resistant hypertension. Hypertension 2013; 61: 457–464.

    Article  CAS  Google Scholar 

  9. Symplicity HTN-1 Investigators. Catheter-based renal sympathetic denervation for resistant hypertension: durability of blood pressure reduction out to 24 months. Hypertension 2011; 57: 911–917.

    Article  Google Scholar 

  10. Esler MD, Krum H, Sobotka PA, Schlaich MP, Schmieder RE, Bohm M . Renal sympathetic denervation in patients with treatment-resistant hypertension (The SymplicityHTN-2 Trial): a randomised controlled trial. Lancet 2010; 376: 1903–1909.

    Article  Google Scholar 

  11. Mahfoud F, Ukena C, Schmieder RE, Cremers B, Rump LC, Vonened O et al. Ambulatory blood pressure changes after renal sympathetic denervation in patients with resistant hypertension. Circulation 2013; 128: 132–140.

    Article  CAS  Google Scholar 

  12. Davies JE, Manisty CH, Petraco R, Barron AJ, Unsworth B, Mayet J et al. First-in-man safety evaluation of renal denervation for chronic systolic heart failure: primary outcome from REACH Pilotstudy. Int J Cardiol 2013; 162: 189–192.

    Article  Google Scholar 

  13. 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: 1163–1170.

    Article  Google Scholar 

  14. Mahfoud F, Schlaich M, Kindermann I, Ukena C, Cremers B, Brandt MC et al. Effect of renal sympathetic denervation on glucose metabolism in patients with resistant hypertension: a pilot study. Circulation 2011; 123: 1940–1946.

    Article  CAS  Google Scholar 

  15. Schlaich MP, Bart B, Hering D, Walton A, Marusic P, Mahfoud F et al. Feasibility of catheter-based renal nerve ablation and effects on sympathetic nerve activity and blood pressure in patients with end-stage renal disease. Int J Cardiol 2013; 168: 2214–2220.

    Article  Google Scholar 

  16. Ukena C, Mahfoud F, Kindermann I, Barth C, Lenski M, Kindermann M et al. Cardiorespiratory response to exercise after renal sympathetic denervation in patients with resistant hypertension. J Am Coll Cardiol 2011; 58: 1176–1182.

    Article  Google Scholar 

  17. Mahfoud F, Cremers B, Janker J, Link B, Vonend O, Ukena C et al. Renal hemodynamics and renal function after catheter-based renal sympathetic denervation in patients with resistant hypertension. Hypertension 2012; 60: 419–424.

    Article  CAS  Google Scholar 

  18. Hering D, Mahfoud F, Walton AS, Krum H, Lambert GW, Lambert EA et al. Renal denervation in moderate to severe CKD. J Am Soc Nephrol 2012; 23: 1250–1257.

    Article  CAS  Google Scholar 

  19. Brandt MC, Mahfoud F, Reda S, Schirmer SH, Erdmann E, Bohm M et al. Renal sympathetic denervation reduces left ventricular hypertrophy and improves cardiac function in patients with resistant hypertension. J Am Coll Cardiol 2012; 59: 901–909.

    Article  Google Scholar 

  20. Templin C, Jaguszewski M, Ghadri JR, Sudano I, Gaehwiler R, Hellermann JP et al. Vascular lesions induced by renal nerve ablation as assessed by optical coherence tomography: pre- and post-procedural comparison with the Simplicity(R) cathetersystem and the EnligHTN multi-electrode renal denervation catheter. Eur Heart J 2013; 34: 2141–2148.

    Article  CAS  Google Scholar 

  21. Rippy MK, Zarins D, Barman NC, Wu A, Duncan KL, Zarins CK . Catheter-based renal sympathetic denervation: chronic preclinical evidence for renal artery safety. Clin Res Cardiol 2011; 100: 1095–01.

    Article  Google Scholar 

  22. Atherton DS, Deep NL, Mendelsohn FO . Micro-anatomy of the renal sympathetic nervous system: a human postmortem histologic study. Clin Anat 2012; 25: 628–633.

    Article  Google Scholar 

  23. DiBona GF, Kopp UC . Neural control of renal function. Physiol Rev 1997; 77: 75–197.

    Article  CAS  Google Scholar 

  24. Stella A, Zanchetti A . Functional role of renal afferents. Physiol Rev 1991; 71: 659–682.

    Article  CAS  Google Scholar 

  25. Krum H, Schlaich M, Sobotka P, Esler M, Mahfoud F, Bohm M et al. Long-term follow up of catheter-based renal denervation for resistant hypertension confirms durable blood pressure reduction. J Am Coll Cardiol 2012; 60: 17–1.

    Article  Google Scholar 

  26. Esler M, Krum H, Schmieder R, Böhm M . Renal sympathetic denervation for treatment of resistant hypertension: two-year update from the Symplicity HTN-2 randomized controlled trial. J Am Coll Cardiol 2013; 61: 10–11.

    Article  Google Scholar 

  27. Doumas M, Anyfanti P, Bakris G . Should ambulatory blood pressure monitoring be mandatory for future studies in resistant hypertension: a perspective. J Hypertens 2012; 30: 874–876.

    Article  CAS  Google Scholar 

  28. Kandzari DE, Bhatt DL, Sobotka PA, O’Neill WW, Esler M, Flack JM et al. Catheter-based renal denervation for resistant hypertension: rationale and design of the SYMPLICITY HTN-3 trial. Clin Cardiol 2012; 35: 528–535.

    Article  Google Scholar 

  29. 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: 2976–2982.

    Article  CAS  Google Scholar 

  30. Brandt MC, Mahfoud F, Reda S, Schirmer SH, Erdmann E, Bohm M et al. Renal sympathetic denervation reduces left ventricular hypertrophy and improves cardiac function in patients with resistant hypertension. J Am Coll Cardiol 2012; 59: 901–909.

    Article  Google Scholar 

  31. Hansen JM, Abildgaard U, Fogh-Andersen N, Kanstrup IL, Bratholm P, Plum I et al. The transplanted human kidney does not achieve functional reinnervation. Clin Sci (Lond) 1994; 87: 13–20.

    Article  CAS  Google Scholar 

  32. Ott C, Mahfoud F, Schmid A, Ditting T, Sobotka PA, Veelken R et al. Renal denervation in moderate treatment resistant hypertension. J Am Coll Cardiol 2013; 62: 1880–1886.

    Article  Google Scholar 

  33. Agabiti-Rosei E, Mancia G, O'Rourke MF, Roman MJ, Safar ME, Smulyan H et al. Central blood pressure measurements and antihypertensive therapy: a consensus document. Hypertension 2007; 50: 154–160.

    Article  CAS  Google Scholar 

  34. Taborsky M, Lazarova ML, Vaclavik J . The effect of renal denervation in patients with advanced heart failure. Eur Heart J 2012; 33, Abstract Supplement 517.

    Google Scholar 

  35. Himmel F, Weil J, Reppel M, Mortensen K, Franzen K, Ansgar L et al. Improved heart rate dynamics in patients undergoing percutaneous renal denervation. J Clin Hypertens (Greenwich) 2012; 14: 654–655.

    Article  Google Scholar 

  36. Ukena C, Mahfoud F, Spies A, Kindermann I, Linz D, Cremers B et al. Effects of renal sympathetic denervation on heart rate and atrioventricular conduction in patients with resistant hypertension. Int J Cardiol 2012; 167: 2846–2851.

    Article  Google Scholar 

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Authors and Affiliations

  1. Apollo Institute for Blood Pressure Management, Apollo Blood Pressure Clinics, Apollo Hospitals, Hyderabad, India

    C V S Ram

  2. Texas Blood Pressure Institute, University of Texas Southwestern Medical School, Dallas, TX, USA

    C V S Ram

  3. Cardiology Department, Continental Hospitals, Hyderabad, India

    A S Kumar

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  1. C V S Ram
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  2. A S Kumar
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Correspondence to C V S Ram.

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Competing interests

Dr CVSR is a consultant to Daiichi-Sankyo, Forest and Medtronic. ASK declares no conflict of interest.

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Ram, C., Kumar, A. Renal denervation therapy for resistant hypertension: a clinical update. J Hum Hypertens 28, 699–704 (2014). https://doi.org/10.1038/jhh.2014.6

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