Skip to main content
SpringerLink
Log in

Pathophysiology: The Target for Renal Denervation

  • Chapter
  • First Online:
Renal Denervation

Abstract

In 1842 the first description of sympathetic nerves surrounding the renal artery was provided in the thesis in Latin by Carl Ludwig [1]. Since then the field became a matter of ongoing scientific interest. Mechanosensitive baroreceptors, volume sensors and chemoreceptors regulate afferent signaling to various nuclei in the brain stem. In the renal arteries both afferent and efferent nerve fibers are found in the adventitia, where they surround the arteries with a netlike appearance [2]. The challenge for renal denervation is to reach the adventitia from the intraluminal side and affecting both efferent and afferent nervous fibers to interrupt the interaction between sensory signals generated in the kidney and central sympathetic outflow [2] (Fig. 1.1). Sympathetic nervous outflow is regulated by the nucleus tractus solitarius located in the midbrain [3]. From there the efferent signaling reaches not only the kidney but also other peripheral structures like the heart, the vessels, the liver and other parts of the central nervous system [3].

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 59.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 79.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Ludwig C. De viribus physicis secretionem urinae adjuvantibus (Latin). Thesis, University of Marburg; 1842.

    Google Scholar 

  2. Sobotka PA, Mahfoud F, Schlaich MP, Hoppe UC, Böhm M, Krum H. Sympatho-renal axis in chronic disease. Clin Res Cardiol. 2011;100:1049–57.

    Article  PubMed Central  PubMed  Google Scholar 

  3. Esler M. The 2009 Carl Ludwig lecture: pathophysiology of the human sympathetic nervous system in cardiovascular diseases: the transition from mechanisms to medical management. J Appl Physiol. 2010;108:227–37.

    Article  CAS  PubMed  Google Scholar 

  4. Katholi RE. Renal nerves in the pathogenesis of hypertension in experimental animals and humans. Am J Physiol. 1983;245:F1–14.

    CAS  PubMed  Google Scholar 

  5. Hering D, Zdrojewski Z, Król E, Kara T, Kucharska W, Somers VK, Rutkowski B, Narkiewicz K. Tonic chemoreflex activation contributes to the elevated muscle sympathetic nerve activity in patients with chronic renal failure. J Hypertens. 2007;25:157–61.

    Article  CAS  PubMed  Google Scholar 

  6. Converse Jr RL, Jacobsen TN, Toto RD, Jost CM, Cosentino F, Fouad-Tarazi F, Victor RG. Sympathetic overactivity in patients with chronic renal failure. N Engl J Med. 1992;327:1912–8.

    Article  PubMed  Google Scholar 

  7. Campese VM. Neurogenic factors and hypertension in chronic renal failure. J Nephrol. 1997;10:184–7.

    CAS  PubMed  Google Scholar 

  8. Hausberg M, Kosch M, Harmelink P, Barenbrock M, Hohage H, Kisters K, Dietl KH, Rahn KH. Sympathetic nerve activity in end-stage renal disease. Circulation. 2002;106:1974–9.

    Article  PubMed  Google Scholar 

  9. Dolezel S. Monoaminergic innervation of the arteries and veins of the kidneys observed using fluorescence reaction. Folia Morphol. 1966;14:168–74.

    CAS  Google Scholar 

  10. Ljungqvist A, Wågermark J. The adrenergic innervation of intrarenal glomerular and extra-glomerular circulatory routes. Nephron. 1970;7:218–29.

    Article  CAS  PubMed  Google Scholar 

  11. Wyss JM, Carlson SH. The role of the central nervous system in hypertension. Curr Hypertens Rep. 1999;1:246–53.

    Article  CAS  PubMed  Google Scholar 

  12. Hering D, Esler MD, Krum H, Mahfoud F, Böhm M, Sobotka PA, Schlaich MP. Recent advances in the treatment of hypertension. Expert Rev Cardiovasc Ther. 2011;9:729–44.

    Article  PubMed  Google Scholar 

  13. Bradley T, Hjemdahl P. Influence of afferent renal nerve activity on contralateral renal overflow of noradrenaline and dopamine to plasma in the dog. Acta Physiol Scand. 1986;128:119–20.

    Article  CAS  PubMed  Google Scholar 

  14. Patel KP, Knuepfer MM. Effect of afferent renal nerve stimulation on blood pressure, heart rate and noradrenergic activity in conscious rats. J Auton Nerv Syst. 1986;17:121–30.

    Article  CAS  PubMed  Google Scholar 

  15. Rogenes PR. Single-unit and multiunit analyses of renorenal reflexes elicited by stimulation of renal chemoreceptors in the rat. J Auton Nerv Syst. 1982;6:143–56.

    Article  CAS  PubMed  Google Scholar 

  16. Bradley T, Hjemdahl P. Further studies on renal nerve stimulation induced release of noradrenaline and dopamine from the canine kidney in situ. Acta Physiol Scand. 1984;122:369–79.

    Article  CAS  PubMed  Google Scholar 

  17. Oliver JA, Pinto J, Sciacca RR, Cannon PJ. Basal norepinephrine overflow into the renal vein: effect of renal nerve stimulation. Am J Physiol. 1980;239:F371–7.

    CAS  PubMed  Google Scholar 

  18. DiBona GF, Esler M. Translational medicine: the antihypertensive effect of renal denervation. Am J Physiol Regul Integr Comp Physiol. 2010;298:R245–53.

    Article  CAS  PubMed  Google Scholar 

  19. Katholi RE, Whitlow PL, Winternitz SR, Oparil S. Importance of the renal nerves in established two-kidney, one clip Goldblatt hypertension. Hypertension. 1982;4:166–74.

    CAS  PubMed  Google Scholar 

  20. Gattone II VH, Siqueira Jr TM, Powell CR, Trambaugh CM, Lingeman JE, Shalhav AL. Contribution of renal innervation to hypertension in rat autosomal dominant polycystic kidney disease. Exp Biol Med. 2008;233:952–95.

    Article  CAS  Google Scholar 

  21. Page IH. The effect on renal efficiency of lowering arterial blood pressure in cases of essential hypertension and nephritis. J Clin Invest. 1934;13:909–15.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Page IH, Heuer GJ. The effect of renal denervation on the level of arterial blood pressure and renal function in essential hypertension. J Clin Invest. 1935;14:27–30.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Smithwick RH, Thompson JE. Splanchnicectomy for essential hypertension; results in 1,266 cases. JAMA. 1953;152:1501–4.

    Article  CAS  Google Scholar 

  24. Krum H, Schlaich M, Whitbourn R, Sobotka PA, Sadowski J, Bartus K, Kapelak B, Walton A, Sievert H, Thambar S, Abraham WT, Esler M. Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study. Lancet. 2009;373:1275–81.

    Article  PubMed  Google Scholar 

  25. Symplicity HTN-2 Investigators, Esler MD, Krum H, Sobotka PA, Schlaich MP, Schmieder RE, Böhm 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  PubMed  Google Scholar 

  26. Krum H, Schlaich MP, Böhm M, Mahfoud F, Rocha-Singh K, Katholi R, Esler MD. Percutaneous renal denervation in patients with treatment-resistant hypertension: final 3-year report of the Symplicity HTN-1 study. Lancet. 2013. doi:10.1016/S0140-6736(13)62192-3. pii: S0140-6736(13)62192-3.

    PubMed  Google Scholar 

  27. Esler MD, Krum H, Schlaich M, Schmieder RE, Böhm M, Sobotka PA, Symplicity HTN-2 Investigators. 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  PubMed  Google Scholar 

  28. Mahfoud F, Ukena C, Schmieder RE, Cremers B, Rump LC, Vonend O, Weil J, Schmidt M, Hoppe UC, Zeller T, Bauer A, Ott C, Blessing E, Sobotka PA, Krum H, Schlaich M, Esler M, Böhm M. Ambulatory blood pressure changes after renal sympathetic denervation in patients with resistant hypertension. Circulation. 2013;128:132–40.

    Article  CAS  PubMed  Google Scholar 

  29. Ott C, Mahfoud F, Schmid A, Ditting T, Sobotka PA, Veelken R, Spies A, Ukena C, Laufs U, Uder M, Böhm M, Schmieder RE. Renal denervation in moderate treatment-resistant hypertension. J Am Coll Cardiol. 2013;62:1880–6.

    Article  PubMed  Google Scholar 

  30. 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.

    Article  CAS  PubMed  Google Scholar 

  31. Doumas M, Douma S. Renal sympathetic denervation: the jury is still out. Lancet. 2010;376:1878–80.

    Article  PubMed  Google Scholar 

  32. Ukena C, Mahfoud F, Kindermann I, Barth C, Lenski M, Kindermann M, Brandt MC, Hoppe UC, Krum H, Esler M, Sobotka PA, Böhm M. Cardiorespiratory response to exercise after renal sympathetic denervation in patients with resistant hypertension. J Am Coll Cardiol. 2011;58:1176–82.

    Article  PubMed  Google Scholar 

  33. Cole CR, Blackstone EH, Pashkow FJ, Snader CE, Lauer MS. Heart-rate recovery immediately after exercise as a predictor of mortality. N Engl J Med. 1999;341:1351–7.

    Article  CAS  PubMed  Google Scholar 

  34. Jouven X, Empana JP, Schwartz PJ, Desnos M, Courbon D, Ducimetière P. Heart-rate profile during exercise as a predictor of sudden death. N Engl J Med. 2005;352:1951–8.

    Article  CAS  PubMed  Google Scholar 

  35. Ukena C, Mahfoud F, Spies A, Kindermann I, Linz D, Cremers B, Laufs U, Neuberger HR, Böhm M, et al. Effects of renal sympathetic denervation on heart rate and atrioventricular conduction in patients with resistant hypertension. Int J Cardiol. 2013;167:2846–51. dx.doi.org/10.1016/j.iicard.2012.07.027.

    Google Scholar 

  36. Smit AA, Halliwill JR, Low PA, Wieling W. Pathophysiological basis of orthostatic hypotension in autonomic failure. J Physiol. 1999;519:1–10.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Laurent S, Schlaich M, Esler M. New drugs, procedures, and devices for hypertension. Lancet. 2012;380:591–600.

    Article  CAS  PubMed  Google Scholar 

  38. Jardine DL, Melton IC, Crozier IG, English S, Bennett SI, Frampton CM, Ikram H. Decrease in cardiac output and muscle sympathetic activity during vasovagal syncope. Am J Physiol Heart Circ Physiol. 2002;282:H1804–9.

    CAS  PubMed  Google Scholar 

  39. Mosqueda-Garcia R, Furlan R, Fernandez-Violante R, Desai T, Snell M, Jarai Z, Ananthram V, Robertson RM, Robertson D. Sympathetic and baroreceptor reflex function in neurally mediated syncope evoked by tilt. J Clin Invest. 1997;99:2736–44.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Morillo CA, Eckberg DL, Ellenbogen KA, Beightol LA, Hoag JB, Tahvanainen KU, Kuusela TA. Diedrich AMVagal and sympathetic mechanisms in patients with orthostatic vasovagal syncope. Circulation. 1997;96:2509–13.

    Article  CAS  PubMed  Google Scholar 

  41. Wallin BG, Sundlöf G. Sympathetic outflow to muscles during vasovagal syncope. J Auton Nerv Syst. 1982;6:287–91.

    Article  CAS  PubMed  Google Scholar 

  42. Lenski M, Mahfoud F, Razouk A, Ukena C, Lenski D, Barth C, Linz D, Laufs U, Kindermann I, Böhm M. Orthostatic function after renal sympathetic denervation in patients with resistant hypertension. Int J Cardiol. 2013;169:418–24.

    Article  PubMed  Google Scholar 

  43. Rafanelli C, Offidani E, Gostoli S, Roncuzzi R. Psychological correlates in patients with different levels of hypertension. Psychiatry Res. 2012;198:154–60.

    Article  PubMed  Google Scholar 

  44. Bajkó Z, Szekeres CC, Kovács KR, Csapó K, Molnár S, Soltész P, Nyitrai E, Magyar MT, Oláh L, Bereczki D, Csiba L. Anxiety, depression and autonomic nervous system dysfunction in hypertension. J Neurol Sci. 2012;317:112–6.

    Article  PubMed  Google Scholar 

  45. Brown ES, Varghese FP, McEwen BS. Association of depression with medical illness: does cortisol play a role? Biol Psychiatry. 2004;55:1–9.

    Article  CAS  PubMed  Google Scholar 

  46. Barton DA, Dawood T, Lambert EA, Esler MD, Haikerwal D, Brenchley C, Socratous F, Kaye DM, Schlaich MP, Hickie I, Lambert GW. Sympathetic activity in major depressive disorder: identifying those at increased cardiac risk? J Hypertens. 2007;25:2117–24.

    Article  CAS  PubMed  Google Scholar 

  47. Lambert GW, Hering D, Esler MD, Marusic P, Lambert EA, Tanamas SK, Shaw J, Krum H, Dixon JB, Barton DA, Schlaich MP. Health-related quality of life after renal denervation in patients with treatment-resistant hypertension. Hypertension. 2012;60:1479–84.

    Article  CAS  PubMed  Google Scholar 

  48. Lenski D, Kindermann I, Lenski M, Ukena C, Bunz M, Mahfoud F, Böhm M. Anxiety, depression, quality of life and stress in patients with resistant hypertension before and after catheter-based renal sympathetic denervation. EuroIntervention. 2013;9:700–8.

    PubMed  Google Scholar 

  49. Böhm M, Linz D, Urban D, Mahfoud F, Ukena C. Renal sympathetic denervation: applications in hypertension and beyond. Nat Rev Cardiol. 2013;10:465–76.

    Article  PubMed  Google Scholar 

  50. Mahfoud F, Cremers B, Janker J, Link B, Vonend O, Ukena C, Linz D, Schmieder R, Rump LC, Kindermann I, Sobotka PA, Krum H, Scheller B, Schlaich M, Laufs U, Böhm M. Renal hemodynamics and renal function after catheter-based renal sympathetic denervation in patients with resistant hypertension. Hypertension. 2012;60:419–24.

    Article  CAS  PubMed  Google Scholar 

  51. Linz D, Mahfoud F, Schotten U, Ukena C, Hohl M, Neuberger HR, Wirth K, Böhm M. Renal sympathetic denervation provides ventricular rate control but does not prevent atrial electrical remodeling during atrial fibrillation. Hypertension. 2013;61:225–31.

    Article  CAS  PubMed  Google Scholar 

  52. Ukena C, Bauer A, Mahfoud F, Schreieck J, Neuberger HR, Eick C, Sobotka PA, Gawaz M, Böhm M. Renal sympathetic denervation for treatment of electrical storm: first-in-man experience. Clin Res Cardiol. 2012;101:63–7.

    Article  PubMed  Google Scholar 

  53. Witkowski A, Prejbisz A, Florczak E, Kądziela J, Śliwiński P, Bieleń P, Michałowska I, Kabat M, Warchoł E, Januszewicz M, Narkiewicz K, Somers VK, Sobotka PA, Januszewicz A. 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.

    Article  CAS  PubMed  Google Scholar 

  54. Brandt MC, Mahfoud F, Reda S, Schirmer SH, Erdmann E, Böhm M, Hoppe UC. Renal sympathetic denervation reduces left ventricular hypertrophy and improves cardiac function in patients with resistant hypertension. J Am Coll Cardiol. 2012;59:901–9.

    Article  PubMed  Google Scholar 

  55. Davies JE, Manisty CH, Petraco R, Barron AJ, Unsworth B, Mayet J, Hamady M, Hughes AD, Sever PS, Sobotka PA, Francis DP. First-in-man safety evaluation of renal denervation for chronic systolic heart failure: primary outcome from REACH-Pilot study. Int J Cardiol. 2013;162:189–92.

    Article  PubMed  Google Scholar 

  56. Mahfoud F, Schlaich M, Kindermann I, Ukena C, Cremers B, Brandt MC, Hoppe UC, Vonend O, Rump LC, Sobotka PA, Krum H, Esler M, Böhm M. Effect of renal sympathetic denervation on glucose metabolism in patients with resistant hypertension: a pilot study. Circulation. 2011;123:1940–6.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cardiology, University Hospital of Saarland, 1 Kirrberger Street, 66420, Homburg/Saar, Germany

    Michael Böhm MD, Dominik Linz MD, PhD, Christian Ukena Dr. med. & Felix Mahfoud MD

Authors
  1. Michael Böhm MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dominik Linz MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christian Ukena Dr. med.
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Felix Mahfoud MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael Böhm MD .

Editor information

Editors and Affiliations

  1. St. Luke's Medical Center, Phoenix, Arizona, USA

    Richard R. Heuser

  2. Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia

    Markus Schlaich

  3. CardioVascular Center Frankfurt Sankt Katharinen, Frankfurt, Germany

    Horst Sievert

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer-Verlag London

About this chapter

Cite this chapter

Böhm, M., Linz, D., Ukena, C., Mahfoud, F. (2015). Pathophysiology: The Target for Renal Denervation. In: Heuser, R., Schlaich, M., Sievert, H. (eds) Renal Denervation. Springer, London. https://doi.org/10.1007/978-1-4471-5223-1_1

Download citation

  • DOI: https://doi.org/10.1007/978-1-4471-5223-1_1

  • Published:

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-4471-5222-4

  • Online ISBN: 978-1-4471-5223-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation