Skip to main content
SpringerLink
Log in
Book cover

Renal Denervation pp 25–43Cite as

The Endpoint on Measuring the Clinical Effects of Renal Denervation: What Are the Best Surrogates

  • Chapter
  • First Online:

  • 895 Accesses

Abstract

In the past several years, renal denervation has proven to be an effective treatment for resistant hypertension (HTN). Unfortunately the procedure does not always lower blood pressure and many patients continue to need drugs for HTN. While there are several potential explanations for this persistent elevation of blood pressure after renal denervation, one is that the renal nerves were not completely ablated. Another is that the HTN was not caused by increased sympathetic nerve activity (SNA) in the individual patient, and that other stimuli for HTN persists after renal denervation. In addition, accumulating evidence suggests that renal denervation also benefits other conditions including heart failure (HF), atrial fibrillation and insulin resistance. Thus in the near future this procedure might be frequently employed for several common medical problems. A major problem is that it will not be sufficient to simply measure blood pressure to ascertain successful renal denervation. Given these considerations, it is apparent that we need surrogate measures of increased sympathetic activity and procedural success. In this chapter we will discuss direct and indirect methods for assessing SNA in humans, how these can be used to screen patients for renal denervation, how they could be used to gauge technical success and how these various methods might be used in specific diseases.

This is a preview of subscription content, 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

Learn about institutional subscriptions

References

  1. Johns EJ, Kopp UC, Dibona GF. Neural control of renal function. Compr Physiol. 2011;1:731–67.

    PubMed  Google Scholar 

  2. 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.

    PubMed  Google Scholar 

  3. Campese VM. Neurogenic factors and hypertension in renal disease. Kidney Int Suppl. 2000;75:S2–6.

    CAS  PubMed  Google Scholar 

  4. Kopp UC. Neural control of renal function. San Rafael: Morgan & Claypool Life Sciences; 2011.

    Google Scholar 

  5. Pernow J, Schwieler J, Kahan T, Hjemdahl P, Oberle J, Wallin BG, Lundberg JM. Influence of sympathetic discharge pattern on norepinephrine and neuropeptide y release. Am J Physiol. 1989;257:H866–72.

    CAS  PubMed  Google Scholar 

  6. Schwartz DD, Malik KU. Renal periarterial nerve stimulation-induced vasoconstriction at low frequencies is primarily due to release of a purinergic transmitter in the rat. J Pharmacol Exp Ther. 1989;250:764–71.

    CAS  PubMed  Google Scholar 

  7. Williams NG, Zhong H, Minneman KP. Differential coupling of alpha1-, alpha2-, and beta-adrenergic receptors to mitogen-activated protein kinase pathways and differentiation in transfected pc12 cells. J Biol Chem. 1998;273:24624–32.

    CAS  PubMed  Google Scholar 

  8. Azroyan A, Morla L, Crambert G, Laghmani K, Ramakrishnan S, Edwards A, Doucet A. Regulation of pendrin by camp: possible involvement in beta-adrenergic-dependent nacl retention. Am J Physiol Renal Physiol. 2012;302:F1180–7.

    CAS  PubMed  Google Scholar 

  9. Pernow J, Lundberg JM. Modulation of noradrenaline and neuropeptide y (npy) release in the pig kidney in vivo: involvement of alpha 2, npy and angiotensin ii receptors. Naunyn Schmiedebergs Arch Pharmacol. 1989;340:379–85.

    CAS  PubMed  Google Scholar 

  10. Unwin RJ, Bailey MA, Burnstock G. Purinergic signaling along the renal tubule: the current state of play. News Physiol Sci Int J Physiol Produced Jointly Int Union Physiol Sci Am Physiol Soc. 2003;18:237–41.

    CAS  Google Scholar 

  11. Barajas L, Powers K, Wang P. Innervation of the renal cortical tubules: a quantitative study. Am J Physiol. 1984;247:F50–60.

    CAS  PubMed  Google Scholar 

  12. Barajas L, Powers K. Innervation of the renal proximal convoluted tubule of the rat. Am J Anat. 1989;186:378–88.

    CAS  PubMed  Google Scholar 

  13. Barajas L, Powers K. Monoaminergic innervation of the rat kidney: a quantitative study. Am J Physiol. 1990;259:F503–11.

    CAS  PubMed  Google Scholar 

  14. Zanchetti AS. Neural regulation of renin release: experimental evidence and clinical implications in arterial hypertension. Circulation. 1977;56:691–8.

    CAS  PubMed  Google Scholar 

  15. Osborn JL, DiBona GF, Thames MD. Beta-1 receptor mediation of renin secretion elicited by low-frequency renal nerve stimulation. J Pharmacol Exp Ther. 1981;216:265–9.

    CAS  PubMed  Google Scholar 

  16. Holmer S, Rinne B, Eckardt KU, Le Hir M, Schricker K, Kaissling B, Riegger G, Kurtz A. Role of renal nerves for the expression of renin in adult rat kidney. Am J Physiol. 1994;266:F738–45.

    CAS  PubMed  Google Scholar 

  17. Barrett CJ, Navakatikyan MA, Malpas SC. Long-term control of renal blood flow: what is the role of the renal nerves? Am J Physiol Regul Integr Comp Physiol. 2001;280:R1534–45.

    CAS  PubMed  Google Scholar 

  18. Abdala AP, McBryde FD, Marina N, Hendy EB, Engelman Z, Fudim M, Sobotka PA, Gourine A, Paton J. Hypertension is critically dependent on the carotid body input in the spontaneously hypertensive rat. J Physiol. 2012;590(Pt 17):4269–77.

    CAS  PubMed Central  PubMed  Google Scholar 

  19. Paton JF, Sobotka PA, Fudim M, Engleman ZJ, Hart EC, McBryde FD, Abdala AP, Marina N, Gourine AV, Lobo M, Patel N, Burchell A, Ratcliffe L, Nightingale A. The carotid body as a therapeutic target for the treatment of sympathetically mediated diseases. Hypertension. 2013;61(1):5–13.

    CAS  PubMed  Google Scholar 

  20. Esler M, Jennings G, Korner P, Willett I, Dudley F, Hasking G, Anderson W, Lambert G. Assessment of human sympathetic nervous system activity from measurements of norepinephrine turnover. Hypertension. 1988;11:3–20.

    CAS  PubMed  Google Scholar 

  21. Lundin S, Ricksten SE, Thoren P. Interaction between “mental stress” and baroreceptor reflexes concerning effects on heart rate, mean arterial pressure and renal sympathetic activity in conscious spontaneously hypertensive rats. Acta Physiol Scand. 1984;120:273–81.

    CAS  PubMed  Google Scholar 

  22. Hasking GJ, Esler MD, Jennings GL, Burton D, Johns JA, Korner PI. Norepinephrine spillover to plasma in patients with congestive heart failure: evidence of increased overall and cardiorenal sympathetic nervous activity. Circulation. 1986;73:615–21.

    CAS  PubMed  Google Scholar 

  23. Ramchandra R, Hood SG, Denton DA, Woods RL, McKinley MJ, McAllen RM, May CN. Basis for the preferential activation of cardiac sympathetic nerve activity in heart failure. Proc Natl Acad Sci U S A. 2009;106:924–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  24. Solano-Flores LP, Rosas-Arellano MP, Ciriello J. Fos induction in central structures after afferent renal nerve stimulation. Brain Res. 1997;753:102–19.

    CAS  PubMed  Google Scholar 

  25. Ciriello J, de Oliveira CV. Renal afferents and hypertension. Curr Hypertens Rep. 2002;4:136–42.

    PubMed  Google Scholar 

  26. Stella A, Zanchetti A. Functional role of renal afferents. Physiol Rev. 1991;71:659–82.

    CAS  PubMed  Google Scholar 

  27. Smits JF, Brody MJ. Activation of afferent renal nerves by intrarenal bradykinin in conscious rats. Am J Physiol. 1984;247:R1003–8.

    CAS  PubMed  Google Scholar 

  28. Katholi RE, Whitlow PL, Hageman GR, Woods WT. Intrarenal adenosine produces hypertension by activating the sympathetic nervous system via the renal nerves in the dog. J Hypertens. 1984;2:349–59.

    CAS  PubMed  Google Scholar 

  29. Campese VM, Kogosov E. Renal afferent denervation prevents hypertension in rats with chronic renal failure. Hypertension. 1995;25:878–82.

    CAS  PubMed  Google Scholar 

  30. 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.

    PubMed  Google Scholar 

  31. Kopp UC, Cicha MZ, Smith LA. Endogenous angiotensin modulates pge(2)-mediated release of substance p from renal mechanosensory nerve fibers. Am J Physiol Regul Integr Comp Physiol. 2002;282:R19–30.

    CAS  PubMed  Google Scholar 

  32. Siddiqi L, Joles JA, Grassi G, Blankestijn PJ. Is kidney ischemia the central mechanism in parallel activation of the renin and sympathetic system? J Hypertens. 2009;27:1341–9.

    CAS  PubMed  Google Scholar 

  33. Gontijo JA, Kopp UC. Activation of renal pelvic chemoreceptors in rats: role of calcitonin gene-related peptide receptors. Acta Physiol Scand. 1999;166:159–65.

    CAS  PubMed  Google Scholar 

  34. Kopp UC, Cicha MZ, Farley DM, Smith LA, Dixon BS. Renal substance p-containing neurons and substance p receptors impaired in hypertension. Hypertension. 1998;31:815–22.

    CAS  PubMed  Google Scholar 

  35. Zhu Y, Xie C, Wang DH. Trpv1-mediated diuresis and natriuresis induced by hypertonic saline perfusion of the renal pelvis. Am J Nephrol. 2007;27:530–7.

    CAS  PubMed  Google Scholar 

  36. Ditting T, Freisinger W, Siegel K, Fiedler C, Small L, Neuhuber W, Heinlein S, Reeh PW, Schmieder RE, Veelken R. Tonic postganglionic sympathetic inhibition induced by afferent renal nerves? Hypertension. 2012;59:467–76.

    CAS  PubMed  Google Scholar 

  37. Feng NH, Lee HH, Shiang JC, Ma MC. Transient receptor potential vanilloid type 1 channels act as mechanoreceptors and cause substance p release and sensory activation in rat kidneys. Am J Physiol Renal Physiol. 2008;294:F316–25.

    CAS  PubMed  Google Scholar 

  38. Fallick C, Sobotka PA, Dunlap ME. Sympathetically mediated changes in capacitance: redistribution of the venous reservoir as a cause of decompensation. Circ Heart Fail. 2011;4:669–75.

    PubMed  Google Scholar 

  39. Bencsath P, Szenasi G, Takacs L. Water and electrolyte transport in henle’s loop and distal tubule after renal sympathectomy in the rat. Am J Physiol. 1985;249:F308–14.

    CAS  PubMed  Google Scholar 

  40. Bachmann S, Bosse HM, Mundel P. Topography of nitric oxide synthesis by localizing constitutive no synthases in mammalian kidney. Am J Physiol. 1995;268:F885–98.

    CAS  PubMed  Google Scholar 

  41. Kopp UC, Cicha MZ, Smith LA. Impaired responsiveness of renal mechanosensory nerves in heart failure: role of endogenous angiotensin. Am J Physiol Regul Integr Comp Physiol. 2003;284:R116–24.

    CAS  PubMed  Google Scholar 

  42. Kline RL, Mercer PF. Functional reinnervation and development of supersensitivity to NE after renal denervation in rats. Am J Physiol. 1980;238:R353–8.

    CAS  PubMed  Google Scholar 

  43. Couch NP, Mc BR, Dammin GJ, Murray JE. Observations on the nature of the enlargement, the regeneration of the nerves, and the function of the canine renal autograft. Br J Exp Pathol. 1961;42:106–13.

    CAS  PubMed Central  PubMed  Google Scholar 

  44. Gazdar AF, Dammin GJ. Neural degeneration and regeneration in human renal transplants. N Engl J Med. 1970;283:222–4.

    CAS  PubMed  Google Scholar 

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

    CAS  Google Scholar 

  46. Mulder J, Hokfelt T, Knuepfer MM, Kopp UC. Renal sensory and sympathetic nerves reinnervate the kidney in a similar time-dependent fashion after renal denervation in rats. Am J Physiol Regul Integr Comp Physiol. 2013;304:R675–82.

    CAS  PubMed Central  PubMed  Google Scholar 

  47. Friberg P, Meredith I, Jennings G, Lambert G, Fazio V, Esler M. Evidence for increased renal norepinephrine overflow during sodium restriction in humans. Hypertension. 1990;16:121–30.

    CAS  PubMed  Google Scholar 

  48. Dunlap ME, Sobotka PA. Fluid re-distribution rather than accumulation causes most cases of decompensated heart failure. J Am Coll Cardiol. 2013;62:165–6.

    PubMed  Google Scholar 

  49. Ma MC, Huang HS, Chen CF. Impaired renal sensory responses after unilateral ureteral obstruction in the rat. J Am Soc Nephrol: JASN. 2002;13:1008–16.

    PubMed  Google Scholar 

  50. Pan HL, Longhurst JC, Eisenach JC, Chen SR. Role of protons in activation of cardiac sympathetic c-fibre afferents during ischaemia in cats. J Physiol. 1999;518(Pt 3):857–66.

    CAS  PubMed Central  PubMed  Google Scholar 

  51. Kostreva DR, Zuperku EJ, Hess GL, Coon RL, Kampine JP. Pulmonary afferent activity recorded from sympathetic nerves. J Appl Physiol. 1975;39:37–40.

    CAS  PubMed  Google Scholar 

  52. Kostreva DR, Castaner A, Kampine JP. Reflex effects of hepatic baroreceptors on renal and cardiac sympathetic nerve activity. Am J Physiol. 1980;238:R390–4.

    CAS  PubMed  Google Scholar 

  53. Vaz M, Jennings G, Turner A, Cox H, Lambert G, Esler M. Regional sympathetic nervous activity and oxygen consumption in obese normotensive human subjects. Circulation. 1997;96:3423–9.

    CAS  PubMed  Google Scholar 

  54. Malpas SC. Sympathetic nervous system overactivity and its role in the development of cardiovascular disease. Physiol Rev. 2010;90:513–57.

    CAS  PubMed  Google Scholar 

  55. Iriki M, Simon E. Differential control of efferent sympathetic activity revisited. J Physiol Sci J Physiol Sci. 2012;62:275–98.

    Google Scholar 

  56. Esler M, Jennings G, Korner P, Blombery P, Sacharias N, Leonard P. Measurement of total and organ-specific norepinephrine kinetics in humans. Am J Physiol. 1984;247:E21–8.

    CAS  PubMed  Google Scholar 

  57. Esler M, Jennings G, Korner P, Blombery P, Burke F, Willett I, Leonard P. Total, and organ-specific, noradrenaline plasma kinetics in essential hypertension. Clin Exp Hypertens A Theory Pract. 1984;6:507–21.

    CAS  Google Scholar 

  58. Esler M, Willett I, Leonard P, Hasking G, Johns J, Little P, Jennings G. Plasma noradrenaline kinetics in humans. J Auton Nerv Syst. 1984;11:125–44.

    CAS  PubMed  Google Scholar 

  59. 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.

    CAS  PubMed  Google Scholar 

  60. Hagbarth KE, Vallbo AB. Pulse and respiratory grouping of sympathetic impulses in human muscle-nerves. Acta Physiol Scand. 1968;74:96–108.

    CAS  PubMed  Google Scholar 

  61. Charkoudian N, Joyner MJ, Johnson CP, Eisenach JH, Dietz NM, Wallin BG. Balance between cardiac output and sympathetic nerve activity in resting humans: role in arterial pressure regulation. J Physiol. 2005;568:315–21.

    CAS  PubMed Central  PubMed  Google Scholar 

  62. Wallin BG, Charkoudian N. Sympathetic neural control of integrated cardiovascular function: insights from measurement of human sympathetic nerve activity. Muscle Nerve. 2007;36:595–614.

    CAS  PubMed  Google Scholar 

  63. Fagius J, Wallin BG. Long-term variability and reproducibility of resting human muscle nerve sympathetic activity at rest, as reassessed after a decade. Clin Auton Res. 1993;3:201–5.

    CAS  PubMed  Google Scholar 

  64. Macefield VG, Wallin BG, Vallbo AB. The discharge behaviour of single vasoconstrictor motoneurones in human muscle nerves. J Physiol. 1994;481(Pt 3):799–809.

    CAS  PubMed Central  PubMed  Google Scholar 

  65. Hering D, Lambert EA, Marusic P, Walton AS, Krum H, Lambert GW, Esler MD, Schlaich MP. Substantial reduction in single sympathetic nerve firing after renal denervation in patients with resistant hypertension. Hypertension. 2013;61:457–64.

    CAS  PubMed  Google Scholar 

  66. Lambert E, Dawood T, Schlaich M, Straznicky N, Esler M, Lambert G. Single-unit sympathetic discharge pattern in pathological conditions associated with elevated cardiovascular risk. Clin Exp Pharmacol Physiol. 2008;35:503–7.

    CAS  PubMed  Google Scholar 

  67. Macefield VG, Wallin BG. Respiratory and cardiac modulation of single sympathetic vasoconstrictor and sudomotor neurones to human skin. J Physiol. 1999;516(Pt 1):303–14.

    CAS  PubMed Central  PubMed  Google Scholar 

  68. Murai H, Takata S, Maruyama M, Nakano M, Kobayashi D, Otowa K, Takamura M, Yuasa T, Sakagami S, Kaneko S. The activity of a single muscle sympathetic vasoconstrictor nerve unit is affected by physiological stress in humans. Am J Physiol Heart Circ Physiol. 2006;290:H853–60.

    CAS  PubMed  Google Scholar 

  69. Macefield VG, Rundqvist B, Sverrisdottir YB, Wallin BG, Elam M. Firing properties of single muscle vasoconstrictor neurons in the sympathoexcitation associated with congestive heart failure. Circulation. 1999;100:1708–13.

    CAS  PubMed  Google Scholar 

  70. Barretto AC, Santos AC, Munhoz R, Rondon MU, Franco FG, Trombetta IC, Roveda F, de Matos LN, Braga AM, Middlekauff HR, Negrao CE. Increased muscle sympathetic nerve activity predicts mortality in heart failure patients. Int J Cardiol. 2009;135:302–7.

    PubMed  Google Scholar 

  71. Parati G, Saul JP, Di Rienzo M, Mancia G. Spectral analysis of blood pressure and heart rate variability in evaluating cardiovascular regulation. A critical appraisal. Hypertension. 1995;25:1276–86.

    CAS  PubMed  Google Scholar 

  72. Task force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Heart rate variability. Standards of measurement, physiological interpretation, and clinical use. Eur Heart J. 1996;17:354–81.

    Google Scholar 

  73. Gilder M, Ramsbottom R. Measures of cardiac autonomic control in women with differing volumes of physical activity. J Sports Sci. 2008;26:781–6.

    PubMed  Google Scholar 

  74. La Rovere MT, Bigger Jr JT, Marcus FI, Mortara A, Schwartz PJ. Baroreflex sensitivity and heart-rate variability in prediction of total cardiac mortality after myocardial infarction. Atrami (autonomic tone and reflexes after myocardial infarction) investigators. Lancet. 1998;351:478–84.

    PubMed  Google Scholar 

  75. Malpas SC. Neural influences on cardiovascular variability: possibilities and pitfalls. Am J Physiol Heart Circ Physiol. 2002;282:H6–20.

    CAS  PubMed  Google Scholar 

  76. Fox K, Borer JS, Camm AJ, Danchin N, Ferrari R, Lopez Sendon JL, Steg PG, Tardif JC, Tavazzi L, Tendera M. Resting heart rate in cardiovascular disease. J Am Coll Cardiol. 2007;50:823–30.

    PubMed  Google Scholar 

  77. Julien C, Chapuis B, Cheng Y, Barres C. Dynamic interactions between arterial pressure and sympathetic nerve activity: role of arterial baroreceptors. Am J Physiol Regul Integr Comp Physiol. 2003;285:R834–41.

    CAS  PubMed  Google Scholar 

  78. Narkiewicz K, Winnicki M, Schroeder K, Phillips BG, Kato M, Cwalina E, Somers VK. Relationship between muscle sympathetic nerve activity and diurnal blood pressure profile. Hypertension. 2002;39:168–72.

    PubMed  Google Scholar 

  79. Parati G, Esler M. The human sympathetic nervous system: its relevance in hypertension and heart failure. Eur Heart J. 2012;33:1058–66.

    CAS  PubMed  Google Scholar 

  80. Bristow JD, Honour AJ, Pickering GW, Sleight P, Smyth HS. Diminished baroreflex sensitivity in high blood pressure. Circulation. 1969;39:48–54.

    CAS  PubMed  Google Scholar 

  81. Ellenbogen KA, Mohanty PK, Szentpetery S, Thames MD. Arterial baroreflex abnormalities in heart failure. Reversal after orthotopic cardiac transplantation. Circulation. 1989;79:51–8.

    CAS  PubMed  Google Scholar 

  82. Parati G, Di Rienzo M, Mancia G. How to measure baroreflex sensitivity: from the cardiovascular laboratory to daily life. J Hypertens. 2000;18:7–19.

    CAS  PubMed  Google Scholar 

  83. Despas F, Lambert E, Vaccaro A, Labrunee M, Franchitto N, Lebrin M, Galinier M, Senard JM, Lambert G, Esler M, Pathak A. Peripheral chemoreflex activation contributes to sympathetic baroreflex impairment in chronic heart failure. J Hypertens. 2012;30:753–60.

    CAS  PubMed  Google Scholar 

  84. Ponikowski P, Chua TP, Anker SD, Francis DP, Doehner W, Banasiak W, Poole-Wilson PA, Piepoli MF, Coats AJ. Peripheral chemoreceptor hypersensitivity: an ominous sign in patients with chronic heart failure. Circulation. 2001;104:544–9.

    CAS  PubMed  Google Scholar 

  85. McBryde FD, Abdala AP, Hendy EB, Pijacka W, Marvar P, Moraes DJ, Sobotka PA, Paton JF. The carotid body as a putative therapeutic target for the treatment of neurogenic hypertension. Nat Commun. 2013;4:2395.

    PubMed  Google Scholar 

  86. Niewinski P, Engelman ZJ, Fudim M, Tubek S, Paleczny B, Jankowska EA, Banasiak W, Sobotka PA, Ponikowski P. Clinical predictors and hemodynamic consequences of elevated peripheral chemosensitivity in optimally treated men with chronic systolic heart failure. J Card Fail. 2013;19:408–15.

    CAS  PubMed  Google Scholar 

  87. Biaggioni I, Olafsson B, Robertson RM, Hollister AS, Robertson D. Cardiovascular and respiratory effects of adenosine in conscious man. Evidence for chemoreceptor activation. Circ Res. 1987;61:779–86.

    CAS  PubMed  Google Scholar 

  88. Stickland MK, Fuhr DP, Haykowsky MJ, Jones KE, Paterson DI, Ezekowitz JA, McMurtry MS. Carotid chemoreceptor modulation of blood flow during exercise in healthy humans. J Physiol. 2011;589:6219–30.

    CAS  PubMed Central  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  90. 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, Bohm M. Ambulatory blood pressure changes after renal sympathetic denervation in patients with resistant hypertension. Circulation. 2013;128:132–40.

    CAS  PubMed  Google Scholar 

  91. Zuern CS, Eick C, Rizas KD, Bauer S, Langer H, Gawaz M, Bauer A. Impaired cardiac baroreflex sensitivity predicts response to renal sympathetic denervation in patients with resistant hypertension. J Am Coll Cardiol. 2013;62(22):2124–30.

    PubMed  Google Scholar 

  92. Rocha-Singh KJ, Katholi RE. Renal sympathetic denervation for treatment-resistant hypertension…in moderation. J Am Coll Cardiol. 2013;62:1887–9.

    PubMed  Google Scholar 

  93. Morlin C, Wallin BG, Eriksson BM. Muscle sympathetic activity and plasma noradrenaline in normotensive and hypertensive man. Acta Physiol Scand. 1983;119:117–21.

    CAS  PubMed  Google Scholar 

  94. Hart EC, McBryde FD, Burchell AE, Ratcliffe LE, Stewart LQ, Baumbach A, Nightingale A, Paton JF. Translational examination of changes in baroreflex function after renal denervation in hypertensive rats and humans. Hypertension. 2013;62(3):533–41.

    CAS  PubMed  Google Scholar 

  95. 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.

    PubMed  Google Scholar 

  96. Chinushi M, Izumi D, Iijima K, Suzuki K, Furushima H, Saitoh O, Furuta Y, Aizawa Y, Iwafuchi M. 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.

    CAS  PubMed  Google Scholar 

  97. Rafiq K, Noma T, Fujisawa Y, Ishihara Y, Arai Y, Nabi AH, Suzuki F, Nagai Y, Nakano D, Hitomi H, Kitada K, Urushihara M, Kobori H, Kohno M, Nishiyama A. Renal sympathetic denervation suppresses de novo podocyte injury and albuminuria in rats with aortic regurgitation. Circulation. 2012;125:1402–13.

    CAS  PubMed Central  PubMed  Google Scholar 

  98. Luippold G, Beilharz M, Muhlbauer B. Chronic renal denervation prevents glomerular hyperfiltration in diabetic rats. Nephrol Dial Transplant. 2004;19:342–7.

    PubMed  Google Scholar 

  99. Clayton SC, Haack KK, Zucker IH. Renal denervation modulates angiotensin receptor expression in the renal cortex of rabbits with chronic heart failure. Am J Physiol Renal Physiol. 2011;300:F31–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  100. Veelken R, Vogel EM, Hilgers K, Amann K, Hartner A, Sass G, Neuhuber W, Tiegs G. Autonomic renal denervation ameliorates experimental glomerulonephritis. J Am Soc Nephrol: JASN. 2008;19:1371–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  101. Wang W, Falk SA, Jittikanont S, Gengaro PE, Edelstein CL, Schrier RW. Protective effect of renal denervation on normotensive endotoxemia-induced acute renal failure in mice. Am J Physiol Renal Physiol. 2002;283:F583–7.

    CAS  PubMed  Google Scholar 

  102. Salman IM, Ameer OZ, Sattar MA, Abdullah NA, Yam MF, Najim HS, Khan AH, Johns EJ. Role of the renal sympathetic nervous system in mediating renal ischaemic injury-induced reductions in renal haemodynamic and excretory functions. Pathology. 2010;42:259–66.

    PubMed  Google Scholar 

  103. van de Borne P. The kidney and the sympathetic system: a short review. Curr Clin Pharmacol. 2013;8(3):175–81.

    PubMed  Google Scholar 

  104. 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.

    CAS  PubMed  Google Scholar 

  105. Ezzahti M, Moelker A, Friesema EC, van der Linde NA, Krestin GP, van den Meiracker AH. Blood pressure and neurohormonal responses to renal nerve ablation in treatment-resistant hypertension. J Hypertens. 2014;32(1):135–41.

    CAS  PubMed  Google Scholar 

  106. Ahmed H, Neuzil P, Skoda J, Petru J, Sediva L, Schejbalova M, Reddy VY. Renal sympathetic denervation using an irrigated radiofrequency ablation catheter for the management of drug-resistant hypertension. JACC Cardiovasc Interv. 2012;5:758–65.

    PubMed  Google Scholar 

  107. Schlaich MP, Bart B, Hering D, Walton A, Marusic P, Mahfoud F, Bohm M, Lambert EA, Krum H, Sobotka PA, Schmieder RE, Ika-Sari C, Eikelis N, Straznicky N, Lambert GW, Esler MD. 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(3):2214–20.

    PubMed  Google Scholar 

  108. Seva Pessoa B, van der Lubbe N, Verdonk K, Roks AJ, Hoorn EJ, Danser AH. Key developments in renin-angiotensin-aldosterone system inhibition. Nat Rev Nephrol. 2013;9:26–36.

    CAS  PubMed  Google Scholar 

  109. Wagman G, Fudim M, Kosmas CE, Panni RE, Vittorio TJ. The neurohormonal network in the raas can bend before breaking. Curr Heart Fail Rep. 2012;9:81–91.

    CAS  PubMed  Google Scholar 

  110. Kowalski R, Kreft E, Kasztan M, Jankowski M, Szczepanska-Konkel M. Chronic renal denervation increases renal tubular response to p2x receptor agonists in rats: implication for renal sympathetic nerve ablation. Nephrol Dial Transplant. 2012;27:3443–8.

    CAS  PubMed  Google Scholar 

  111. Christy IJ, Denton KM, Anderson WP. Renal denervation potentiates the natriuretic and diuretic effects of atrial natriuretic peptide in anaesthetized rabbits. Clin Exp Pharmacol Physiol. 1994;21:41–8.

    CAS  PubMed  Google Scholar 

  112. Kompanowska-Jezierska E, Walkowska A, Johns EJ, Sadowski J. Early effects of renal denervation in the anaesthetised rat: natriuresis and increased cortical blood flow. J Physiol. 2001;531:527–34.

    CAS  PubMed Central  PubMed  Google Scholar 

  113. Pettersson A, Hedner J, Hedner T. Renal interaction between sympathetic activity and anp in rats with chronic ischaemic heart failure. Acta Physiol Scand. 1989;135:487–92.

    CAS  PubMed  Google Scholar 

  114. Wenting GJ, Blankestijn PJ, Poldermans D, van Geelen J, Derkx FH, Man in’t Veld AJ, Schalekamp MA. Blood pressure response of nephrectomized subjects and patients with essential hypertension to ramipril: indirect evidence that inhibition of tissue angiotensin converting enzyme is important. Am J Cardiol. 1987;59:92D–7.

    CAS  PubMed  Google Scholar 

  115. Wang L, Lu CZ, Zhang X, Luo D, Zhao B, Yu X, Xia DS, Chen X, Zhao XD. The effect of catheter based renal synthetic denervation on renin-angiotensin-aldosterone system in patients with resistant hypertension. Zhonghua Xin Xue Guan Bing Za Zhi. 2013;41:3–7.

    PubMed  Google Scholar 

  116. Di Daniele N, De Francesco M, Violo L, Spinelli A, Simonetti G. Renal sympathetic nerve ablation for the treatment of difficult-to-control or refractory hypertension in a haemodialysis patient. Nephrol Dial Transplant. 2012;27:1689–90.

    PubMed  Google Scholar 

  117. Masuo K, Lambert GW, Esler MD, Rakugi H, Ogihara T, Schlaich MP. The role of sympathetic nervous activity in renal injury and end-stage renal disease. Hypertens Res. 2010;33:521–8.

    CAS  PubMed  Google Scholar 

  118. 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.

    PubMed  Google Scholar 

  119. Hering D, Lambert EA, Marusic P, Ika-Sari C, Walton AS, Krum H, Sobotka PA, Mahfoud F, Bohm M, Lambert GW, Esler MD, Schlaich MP. Renal nerve ablation reduces augmentation index in patients with resistant hypertension. J Hypertens. 2013;31(9):1893–900.

    CAS  PubMed  Google Scholar 

  120. Greenwood JP, Stoker JB, Mary DA. Single-unit sympathetic discharge: quantitative assessment in human hypertensive disease. Circulation. 1999;100:1305–10.

    CAS  PubMed  Google Scholar 

  121. Oliveira VL, Irigoyen MC, Moreira ED, Strunz C, Krieger EM. Renal denervation normalizes pressure and baroreceptor reflex in high renin hypertension in conscious rats. Hypertension. 1992;19:II17–21.

    CAS  PubMed  Google Scholar 

  122. Janssen BJ, van Essen H, Vervoort-Peters LH, Struyker-Boudier HA, Smits JF. Role of afferent renal nerves in spontaneous hypertension in rats. Hypertension. 1989;13:327–33.

    CAS  PubMed  Google Scholar 

  123. Schiller ACP, Haack K, Zucker I. Unilateral renal denervation enhances baroreflex function in concious rabbits with chronic heart failure. Physiologist. 2012;55:A13.19.43.

    Google Scholar 

  124. Brinkmann J, Heusser K, Schmidt BM, Menne J, Klein G, Bauersachs J, Haller H, Sweep FC, Diedrich A, Jordan J, Tank J. Catheter-based renal nerve ablation and centrally generated sympathetic activity in difficult-to-control hypertensive patients: prospective case series. Hypertension. 2012;60:1485–90.

    CAS  PubMed  Google Scholar 

  125. Fujisawa Y, Nagai Y, Lei B, Nakano D, Fukui T, Hitomi H, Mori H, Masaki T, Nishiyama A. Roles of central renin-angiotensin system and afferent renal nerve in the control of systemic hemodynamics in rats. Hypertens Res. 2011;34:1228–32.

    CAS  PubMed  Google Scholar 

  126. Ito S, Komatsu K, Tsukamoto K, Kanmatsuse K, Sved AF. Ventrolateral medulla at1 receptors support blood pressure in hypertensive rats. Hypertension. 2002;40:552–9.

    CAS  PubMed  Google Scholar 

  127. Weyhenmeyer JA, Phillips MI. Angiotensin-like immunoreactivity in the brain of the spontaneously hypertensive rat. Hypertension. 1982;4:514–23.

    CAS  PubMed  Google Scholar 

  128. Krum H, Barman N, Schlaich M, Sobotka P, Esler M, Mahfoud F, Bohm M, Dunlap M, Sadowski J, Bartus K, Kapelak B, Rocha-Singh KJ, Katholi RE,Witkowski A, Kadziela J, Januszewicz A, Prejbisz A, Walton AS, Sievert H, Id D, Wunderlich N, Whitbourn R, Rump LC, Vonend O, Saleh A, Thambar S, Nanra R, Zeller T, Erglis A, Sagic D, Boskovic S, Brachmann J, Schmidt M, Wenzel UO, Bart BA, Schmieder RE, Scheinert D, Börgel J, Straley C. Catheter-based renal sympathetic denervation for resistant hypertension: durability of blood pressure reduction out to 24 months. Hypertension. 2011;57:911–7.

    CAS  Google Scholar 

  129. Ukena C, Mahfoud F, Spies A, Kindermann I, Linz D, Cremers B, Laufs U, Neuberger HR, Bohm M. Effects of renal sympathetic denervation on heart rate and atrioventricular conduction in patients with resistant hypertension. Int J Cardiol. 2013;167(6):2846–51.

    PubMed  Google Scholar 

  130. Brandt MC, Reda S, Mahfoud F, Lenski M, Bohm M, Hoppe UC. Effects of renal sympathetic denervation on arterial stiffness and central hemodynamics in patients with resistant hypertension. J Am Coll Cardiol. 2012;60:1956–65.

    PubMed  Google Scholar 

  131. Huang WC, Fang TC, Cheng JT. Renal denervation prevents and reverses hyperinsulinemia-induced hypertension in rats. Hypertension. 1998;32:249–54.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  134. 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, Bohm M. Renal hemodynamics and renal function after catheter-based renal sympathetic denervation in patients with resistant hypertension. Hypertension. 2012;60:419–24.

    CAS  PubMed  Google Scholar 

  135. Schmieder RE, Mann JF, Schumacher H, Gao P, Mancia G, Weber MA, McQueen M, Koon T, Yusuf S. Changes in albuminuria predict mortality and morbidity in patients with vascular disease. J Am Soc Nephrol: JASN. 2011;22:1353–64.

    PubMed Central  PubMed  Google Scholar 

  136. Villarreal D, Freeman RH, Johnson RA, Simmons JC. Effects of renal denervation on postprandial sodium excretion in experimental heart failure. Am J Physiol. 1994;266:R1599–604.

    CAS  PubMed  Google Scholar 

  137. Brandt MC, Mahfoud F, Reda S, Schirmer SH, Erdmann E, Bohm 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.

    PubMed  Google Scholar 

  138. 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.

    PubMed  Google Scholar 

  139. Linz D, Schotten U, Neuberger HR, Bohm M, Wirth K. Negative tracheal pressure during obstructive respiratory events promotes atrial fibrillation by vagal activation. Heart Rhythm. 2011;8:1436–43.

    PubMed  Google Scholar 

  140. Linz D, Mahfoud F, Schotten U, Ukena C, Neuberger HR, Wirth K, Bohm M. Renal sympathetic denervation suppresses postapneic blood pressure rises and atrial fibrillation in a model for sleep apnea. Hypertension. 2012;60:172–8.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  142. Pokushalov E, Romanov A, Corbucci G, Artyomenko S, Baranova V, Turov A, Shirokova N, Karaskov A, Mittal S, Steinberg JS. 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.

    PubMed  Google Scholar 

  143. 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.

    PubMed  Google Scholar 

  144. Law MR, Morris JK, Wald NJ. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies. BMJ. 2009;338:b1665.

    CAS  PubMed Central  PubMed  Google Scholar 

  145. Ohkubo T, Imai Y, Tsuji I, Nagai K, Watanabe N, Minami N, Itoh O, Bando T, Sakuma M, Fukao A, Satoh H, Hisamichi S, Abe K. Prediction of mortality by ambulatory blood pressure monitoring versus screening blood pressure measurements: a pilot study in ohasama. J Hypertens. 1997;15:357–64.

    CAS  PubMed  Google Scholar 

  146. Pickering TG, Shimbo D, Haas D. Ambulatory blood-pressure monitoring. N Engl J Med. 2006;354:2368–74.

    CAS  PubMed  Google Scholar 

  147. Mancia G, Zanchetti A, Agabiti-Rosei E, Benemio G, De Cesaris R, Fogari R, Pessina A, Porcellati C, Rappelli A, Salvetti A, Trimarco B. Ambulatory blood pressure is superior to clinic blood pressure in predicting treatment-induced regression of left ventricular hypertrophy. Sample study group. Study on ambulatory monitoring of blood pressure and lisinopril evaluation. Circulation. 1997;95:1464–70.

    CAS  PubMed  Google Scholar 

  148. Mancia G, Parati G. Ambulatory blood pressure monitoring and organ damage. Hypertension. 2000;36:894–900.

    CAS  PubMed  Google Scholar 

  149. Fagard RH, Celis H, Thijs L, Staessen JA, Clement DL, De Buyzere ML, De Bacquer DA. Daytime and nighttime blood pressure as predictors of death and cause-specific cardiovascular events in hypertension. Hypertension. 2008;51:55–61.

    CAS  PubMed  Google Scholar 

  150. Metoki H, Ohkubo T, Kikuya M, Asayama K, Obara T, Hashimoto J, Totsune K, Hoshi H, Satoh H, Imai Y. Prognostic significance for stroke of a morning pressor surge and a nocturnal blood pressure decline: the Ohasama study. Hypertension. 2006;47:149–54.

    CAS  PubMed  Google Scholar 

  151. Dolan E, Stanton A, Thijs L, Hinedi K, Atkins N, McClory S, Den Hond E, McCormack P, Staessen JA, O’Brien E. Superiority of ambulatory over clinic blood pressure measurement in predicting mortality: the Dublin outcome study. Hypertension. 2005;46:156–61.

    CAS  PubMed  Google Scholar 

  152. Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, Grassi G, Heagerty AM, Kjeldsen SE, Laurent S, Narkiewicz K, Ruilope L, Rynkiewicz A, Schmieder RE, Struijker Boudier HA, Zanchetti A, Vahanian A, Camm J, De Caterina R, Dean V, Dickstein K, Filippatos G, Funck-Brentano C, Hellemans I, Kristensen SD, McGregor K, Sechtem U, Silber S, Tendera M, Widimsky P, Zamorano JL, Erdine S, Kiowski W, Agabiti-Rosei E, Ambrosioni E, Lindholm LH, Manolis A, Nilsson PM, Redon J, Struijker-Boudier HA, Viigimaa M, Adamopoulos S, Bertomeu V, Clement D, Farsang C, Gaita D, Lip G, Mallion JM, Manolis AJ, O’Brien E, Ponikowski P, Ruschitzka F, Tamargo J, van Zwieten P, Waeber B, Williams B, The task force for the management of arterial hypertension of the European Society of H, The task force for the management of arterial hypertension of the European Society of C. 2007 guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European Society of Hypertension (esh) and of the European Society of Cardiology (esc). Eur Heart J. 2007;28:1462–536.

    PubMed  Google Scholar 

  153. Williams B, Lacy PS, Thom SM, Cruickshank K, Stanton A, Collier D, Hughes AD, Thurston H, O’Rourke M. Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes: principal results of the conduit artery function evaluation (cafe) study. Circulation. 2006;113:1213–25.

    CAS  PubMed  Google Scholar 

  154. Lindholm LH, Carlberg B, Samuelsson O. Should beta blockers remain first choice in the treatment of primary hypertension? A meta-analysis. Lancet. 2005;366:1545–53.

    CAS  PubMed  Google Scholar 

  155. Mancia G, Parati G. Office compared with ambulatory blood pressure in assessing response to antihypertensive treatment: a meta-analysis. J Hypertens. 2004;22:435–45.

    CAS  PubMed  Google Scholar 

  156. Zuern CS, Rizas KD, Eick C, Stoleriu C, Bunk L, Barthel P, Balletshofer B, Gawaz M, Bauer A. Effects of renal sympathetic denervation on 24-hour blood pressure variability. Front Physiol. 2012;3:134.

    PubMed Central  PubMed  Google Scholar 

  157. Parati G, Pomidossi G, Albini F, Malaspina D, Mancia G. Relationship of 24-hour blood pressure mean and variability to severity of target-organ damage in hypertension. J Hypertens. 1987;5:93–8.

    CAS  PubMed  Google Scholar 

  158. Kikuya M, Hozawa A, Ohokubo T, Tsuji I, Michimata M, Matsubara M, Ota M, Nagai K, Araki T, Satoh H, Ito S, Hisamichi S, Imai Y. Prognostic significance of blood pressure and heart rate variabilities: the Ohasama study. Hypertension. 2000;36:901–6.

    CAS  PubMed  Google Scholar 

  159. Muntner P, Shimbo D, Tonelli M, Reynolds K, Arnett DK, Oparil S. The relationship between visit-to-visit variability in systolic blood pressure and all-cause mortality in the general population: findings from nhanes iii, 1988 to 1994. Hypertension. 2011;57:160–6.

    CAS  PubMed  Google Scholar 

  160. Hsieh YT, Tu ST, Cho TJ, Chang SJ, Chen JF, Hsieh MC. Visit-to-visit variability in blood pressure strongly predicts all-cause mortality in patients with type 2 diabetes: a 5.5-year prospective analysis. Eur J Clin Invest. 2012;42:245–53.

    PubMed  Google Scholar 

  161. Perticone F, Ceravolo R, Pujia A, Ventura G, Iacopino S, Scozzafava A, Ferraro A, Chello M, Mastroroberto P, Verdecchia P, Schillaci G. Prognostic significance of endothelial dysfunction in hypertensive patients. Circulation. 2001;104:191–6.

    CAS  PubMed  Google Scholar 

  162. Redfield MM, Jacobsen SJ, Burnett Jr JC, Mahoney DW, Bailey KR, Rodeheffer RJ. Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. JAMA: J Am Med Assoc. 2003;289:194–202.

    Google Scholar 

  163. Bombelli M, Facchetti R, Carugo S, Madotto F, Arenare F, Quarti-Trevano F, Capra A, Giannattasio C, Dell’Oro R, Grassi G, Sega R, Mancia G. Left ventricular hypertrophy increases cardiovascular risk independently of in-office and out-of-office blood pressure values. J Hypertens. 2009;27:2458–64.

    CAS  PubMed  Google Scholar 

  164. Koren MJ, Devereux RB, Casale PN, Savage DD, Laragh JH. Relation of left ventricular mass and geometry to morbidity and mortality in uncomplicated essential hypertension. Ann Intern Med. 1991;114:345–52.

    CAS  PubMed  Google Scholar 

  165. Okin PM, Devereux RB, Jern S, Kjeldsen SE, Julius S, Nieminen MS, Snapinn S, Harris KE, Aurup P, Edelman JM, Wedel H, Lindholm LH, Dahlof B. Regression of electrocardiographic left ventricular hypertrophy during antihypertensive treatment and the prediction of major cardiovascular events. JAMA: J Am Med Assoc. 2004;292:2343–9.

    CAS  Google Scholar 

  166. Pierdomenico SD, Cuccurullo F. Risk reduction after regression of echocardiographic left ventricular hypertrophy in hypertension: a meta-analysis. Am J Hypertens. 2010;23:876–81.

    PubMed  Google Scholar 

  167. Vakili BA, Okin PM, Devereux RB. Prognostic implications of left ventricular hypertrophy. Am Heart J. 2001;141:334–41.

    CAS  PubMed  Google Scholar 

  168. Mathew J, Sleight P, Lonn E, Johnstone D, Pogue J, Yi Q, Bosch J, Sussex B, Probstfield J, Yusuf S, Heart Outcomes Prevention Evaluation I. Reduction of cardiovascular risk by regression of electrocardiographic markers of left ventricular hypertrophy by the angiotensin-converting enzyme inhibitor ramipril. Circulation. 2001;104:1615–21.

    CAS  PubMed  Google Scholar 

  169. Mancini GB, Dahlof B, Diez J. Surrogate markers for cardiovascular disease: structural markers. Circulation. 2004;109:IV22–30.

    PubMed  Google Scholar 

  170. Devereux RB, Agabiti-Rosei E, Dahlof B, Gosse P, Hahn RT, Okin PM, Roman MJ. Regression of left ventricular hypertrophy as a surrogate end-point for morbid events in hypertension treatment trials. J Hypertens Suppl. 1996;14:S95–101; discussion S101–2.

    CAS  PubMed  Google Scholar 

  171. Dahlof B, Devereux R, de Faire U, Fyhrquist F, Hedner T, Ibsen H, Julius S, Kjeldsen S, Kristianson K, Lederballe-Pedersen O, Lindholm LH, Nieminen MS, Omvik P, Oparil S, Wedel H. The losartan intervention for endpoint reduction (life) in hypertension study: rationale, design, and methods. The life study group. Am J Hypertens. 1997;10:705–13.

    CAS  PubMed  Google Scholar 

  172. Okin PM, Devereux RB, Jern S, Kjeldsen SE, Julius S, Nieminen MS, Snapinn S, Harris KE, Aurup P, Edelman JM, Wedel H, Lindholm LH, Dahlof B, Investigators LS. Regression of electrocardiographic left ventricular hypertrophy during antihypertensive treatment and the prediction of major cardiovascular events. JAMA: J Am Med Assoc. 2004;292:2343–9.

    CAS  Google Scholar 

  173. Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med. 1990;322:1561–6.

    CAS  PubMed  Google Scholar 

  174. Bikkina M, Levy D, Evans JC, Larson MG, Benjamin EJ, Wolf PA, Castelli WP. Left ventricular mass and risk of stroke in an elderly cohort. The Framingham Heart Study. JAMA: J Am Med Assoc. 1994;272:33–6.

    CAS  Google Scholar 

  175. Liao Y, Cooper RS, McGee DL, Mensah GA, Ghali JK. The relative effects of left ventricular hypertrophy, coronary artery disease, and ventricular dysfunction on survival among black adults. JAMA: J Am Med Assoc. 1995;273:1592–7.

    CAS  Google Scholar 

  176. Ghali JK, Liao Y, Simmons B, Castaner A, Cao G, Cooper RS. The prognostic role of left ventricular hypertrophy in patients with or without coronary artery disease. Ann Intern Med. 1992;117:831–6.

    CAS  PubMed  Google Scholar 

  177. Bolognese L, Dellavesa P, Rossi L, Sarasso G, Bongo AS, Scianaro MC. Prognostic value of left ventricular mass in uncomplicated acute myocardial infarction and one-vessel coronary artery disease. Am J Cardiol. 1994;73:1–5.

    CAS  PubMed  Google Scholar 

  178. Fagard RH, Pardaens K, Staessen JA, Thijs L. Prognostic value of invasive hemodynamic measurements at rest and during exercise in hypertensive men. Hypertension. 1996;28:31–6.

    CAS  PubMed  Google Scholar 

  179. Kokkinos P, Myers J, Faselis C, Panagiotakos DB, Doumas M, Pittaras A, Manolis A, Kokkinos JP, Karasik P, Greenberg M, Papademetriou V, Fletcher R. Exercise capacity and mortality in older men: a 20-year follow-up study. Circulation. 2010;122:790–7.

    PubMed  Google Scholar 

  180. Blacher J, Guerin AP, Pannier B, Marchais SJ, Safar ME, London GM. Impact of aortic stiffness on survival in end-stage renal disease. Circulation. 1999;99:2434–9.

    CAS  PubMed  Google Scholar 

  181. Laurent S, Boutouyrie P, Asmar R, Gautier I, Laloux B, Guize L, Ducimetiere P, Benetos A. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension. 2001;37:1236–41.

    CAS  PubMed  Google Scholar 

  182. Willum-Hansen T, Staessen JA, Torp-Pedersen C, Rasmussen S, Thijs L, Ibsen H, Jeppesen J. Prognostic value of aortic pulse wave velocity as index of arterial stiffness in the general population. Circulation. 2006;113:664–70.

    PubMed  Google Scholar 

  183. Laurent S, Cockcroft J, Van Bortel L, Boutouyrie P, Giannattasio C, Hayoz D, Pannier B, Vlachopoulos C, Wilkinson I, Struijker-Boudier H. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J. 2006;27:2588–605.

    PubMed  Google Scholar 

  184. London GM, Blacher J, Pannier B, Guerin AP, Marchais SJ, Safar ME. Arterial wave reflections and survival in end-stage renal failure. Hypertension. 2001;38:434–8.

    CAS  PubMed  Google Scholar 

  185. Weber T, Auer J, O’Rourke MF, Kvas E, Lassnig E, Berent R, Eber B. Arterial stiffness, wave reflections, and the risk of coronary artery disease. Circulation. 2004;109:184–9.

    PubMed  Google Scholar 

  186. Tropeano AI, Boutouyrie P, Pannier B, Joannides R, Balkestein E, Katsahian S, Laloux B, Thuillez C, Struijker-Boudier H, Laurent S. Brachial pressure-independent reduction in carotid stiffness after long-term angiotensin-converting enzyme inhibition in diabetic hypertensives. Hypertension. 2006;48:80–6.

    CAS  PubMed  Google Scholar 

  187. Karalliedde J, Smith A, DeAngelis L, Mirenda V, Kandra A, Botha J, Ferber P, Viberti G. Valsartan improves arterial stiffness in type 2 diabetes independently of blood pressure lowering. Hypertension. 2008;51:1617–23.

    CAS  PubMed  Google Scholar 

  188. Stewart AD, Jiang B, Millasseau SC, Ritter JM, Chowienczyk PJ. Acute reduction of blood pressure by nitroglycerin does not normalize large artery stiffness in essential hypertension. Hypertension. 2006;48:404–10.

    CAS  PubMed  Google Scholar 

  189. Gillman MW, Kannel WB, Belanger A, D’Agostino RB. Influence of heart rate on mortality among persons with hypertension: the Framingham Study. Am Heart J. 1993;125:1148–54.

    CAS  PubMed  Google Scholar 

  190. Wannamethee G, Shaper AG, Macfarlane PW. Heart rate, physical activity, and mortality from cancer and other noncardiovascular diseases. Am J Epidemiol. 1993;137:735–48.

    CAS  PubMed  Google Scholar 

  191. Bohm M, Swedberg K, Komajda M, Borer JS, Ford I, Dubost-Brama A, Lerebours G, Tavazzi L. Heart rate as a risk factor in chronic heart failure (shift): the association between heart rate and outcomes in a randomised placebo-controlled trial. Lancet. 2010;376:886–94.

    PubMed  Google Scholar 

  192. Reil JC, Custodis F, Swedberg K, Komajda M, Borer JS, Ford I, Tavazzi L, Laufs U, Bohm M. Heart rate reduction in cardiovascular disease and therapy. Clin Res Cardiol. 2011;100:11–9.

    PubMed  Google Scholar 

  193. Kannel WB, Kannel C, Paffenbarger Jr RS, Cupples LA. Heart rate and cardiovascular mortality: the Framingham study. Am Heart J. 1987;113:1489–94.

    CAS  PubMed  Google Scholar 

  194. Swedberg K, Komajda M, Bohm M, Borer JS, Ford I, Dubost-Brama A, Lerebours G, Tavazzi L. Ivabradine and outcomes in chronic heart failure (shift): a randomised placebo-controlled study. Lancet. 2010;376:875–85.

    CAS  PubMed  Google Scholar 

  195. Bohm M, Borer J, Ford I, Gonzalez-Juanatey JR, Komajda M, Lopez-Sendon J, Reil JC, Swedberg K, Tavazzi L. Heart rate at baseline influences the effect of ivabradine on cardiovascular outcomes in chronic heart failure: analysis from the shift study. Clin Res Cardiol. 2013;102:11–22.

    PubMed  Google Scholar 

  196. He B, Scherlag BJ, Nakagawa H, Lazzara R, Po SS. The intrinsic autonomic nervous system in atrial fibrillation: a review. ISRN Cardiol. 2012;2012:490674.

    PubMed Central  PubMed  Google Scholar 

  197. Podrid PJ, Fuchs T, Candinas R. Role of the sympathetic nervous system in the genesis of ventricular arrhythmia. Circulation. 1990;82:I103–13.

    CAS  PubMed  Google Scholar 

  198. Knecht S, O’Neill MD, Verbeet T. Rhythm control versus rate control for atrial fibrillation. N Engl J Med. 2008;359:1522; author reply 1522.

    PubMed  Google Scholar 

  199. Benjamin EJ, Wolf PA, D’Agostino RB, Silbershatz H, Kannel WB, Levy D. Impact of atrial fibrillation on the risk of death: the Framingham heart study. Circulation. 1998;98:946–52.

    CAS  PubMed  Google Scholar 

  200. Kirchhof P, Auricchio A, Bax J, Crijns H, Camm J, Diener HC, Goette A, Hindricks G, Hohnloser S, Kappenberger L, Kuck KH, Lip GY, Olsson B, Meinertz T, Priori S, Ravens U, Steinbeck G, Svernhage E, Tijssen J, Vincent A, Breithardt G. Outcome parameters for trials in atrial fibrillation: executive summary. Eur Heart J. 2007;28:2803–17.

    PubMed  Google Scholar 

  201. Linz D, Wirth K, Ukena C, Mahfoud F, Poss J, Linz B, Bohm M, Neuberger HR. Renal denervation suppresses ventricular arrhythmias during acute ventricular ischemia in pigs. Heart Rhythm. 2013;10(10):1525–30.

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  203. Daviglus ML, Liao Y, Greenland P, Dyer AR, Liu K, Xie X, Huang CF, Prineas RJ, Stamler J. Association of nonspecific minor st-t abnormalities with cardiovascular mortality: the Chicago Western Electric Study. JAMA: J Am Med Assoc. 1999;281:530–6.

    CAS  Google Scholar 

  204. de Groot E, Hovingh GK, Wiegman A, Duriez P, Smit AJ, Fruchart JC, Kastelein JJ. Measurement of arterial wall thickness as a surrogate marker for atherosclerosis. Circulation. 2004;109:III33–8.

    PubMed  Google Scholar 

  205. Danesh J, Wheeler JG, Hirschfield GM, Eda S, Eiriksdottir G, Rumley A, Lowe GD, Pepys MB, Gudnason V. C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. N Engl J Med. 2004;350:1387–97.

    CAS  PubMed  Google Scholar 

  206. Klein IH, Ligtenberg G, Neumann J, Oey PL, Koomans HA, Blankestijn PJ. Sympathetic nerve activity is inappropriately increased in chronic renal disease. J Am Soc Nephrol: JASN. 2003;14:3239–44.

    PubMed  Google Scholar 

  207. Wen CP, Cheng TY, Tsai MK, Chang YC, Chan HT, Tsai SP, Chiang PH, Hsu CC, Sung PK, Hsu YH, Wen SF. All-cause mortality attributable to chronic kidney disease: a prospective cohort study based on 462 293 adults in Taiwan. Lancet. 2008;371:2173–82.

    PubMed  Google Scholar 

  208. Weiner DE, Tabatabai S, Tighiouart H, Elsayed E, Bansal N, Griffith J, Salem DN, Levey AS, Sarnak MJ. Cardiovascular outcomes and all-cause mortality: exploring the interaction between ckd and cardiovascular disease. Am J Kidney Dis. 2006;48:392–401.

    PubMed  Google Scholar 

  209. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004;351:1296–305.

    CAS  PubMed  Google Scholar 

  210. Matsushita K, van der Velde M, Astor BC, Woodward M, Levey AS, de Jong PE, Coresh J, Gansevoort RT. Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. Lancet. 2010;375:2073–81.

    PubMed Central  PubMed  Google Scholar 

  211. Wang Y, Seto SW, Golledge J. Therapeutic effects of renal denervation on renal failure. Curr Neurovasc Res. 2013;10:172–84.

    PubMed  Google Scholar 

  212. Ott C, Janka R, Schmid A, Titze S, Ditting T, Sobotka PA, Veelken R, Uder M, Schmieder RE. Vascular and renal hemodynamic changes after renal denervation. Clin J Am Soc Nephrol: CJASN. 2013;8:1195–201.

    PubMed Central  PubMed  Google Scholar 

  213. Hering D, Mahfoud F, Walton AS, Krum H, Lambert GW, Lambert EA, Sobotka PA, Bohm M, Cremers B, Esler MD, Schlaich MP. Renal denervation in moderate to severe ckd. J Am Soc Nephrol: JASN. 2012;23:1250–7.

    CAS  PubMed Central  PubMed  Google Scholar 

  214. Ott C, Schmid A, Ditting T, Sobotka PA, Veelken R, Uder M, Schmieder RE. Renal denervation in a hypertensive patient with end-stage renal disease and small arteries: a direction for future research. J Clin Hypertens (Greenwich). 2012;14:799–801.

    Google Scholar 

  215. Mancia G, Bousquet P, Elghozi JL, Esler M, Grassi G, Julius S, Reid J, Van Zwieten PA. The sympathetic nervous system and the metabolic syndrome. J Hypertens. 2007;25:909–20.

    CAS  PubMed  Google Scholar 

  216. Huggett RJ, Scott EM, Gilbey SG, Stoker JB, Mackintosh AF, Mary DA. Impact of type 2 diabetes mellitus on sympathetic neural mechanisms in hypertension. Circulation. 2003;108:3097–101.

    CAS  PubMed  Google Scholar 

  217. Esler M, Rumantir M, Wiesner G, Kaye D, Hastings J, Lambert G. Sympathetic nervous system and insulin resistance: from obesity to diabetes. Am J Hypertens. 2001;14:304S–9.

    CAS  PubMed  Google Scholar 

  218. Isomaa B, Almgren P, Tuomi T, Forsen B, Lahti K, Nissen M, Taskinen MR, Groop L. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care. 2001;24:683–9.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Cardiology, Department of Medicine, The Ohio State University, 2015 Marywood Lane, West St. Paul, MN, 55118, USA

    Paul A. Sobotka MD

  2. Medicine and Pharmacology, Vanderbilt Medical Center, Room 536, Robinson Research Bldg, Nashville, TN, 37232-6602, USA

    David G. Harrison MD

  3. Internal Medicine, Vanderbilt Medical Center, D-3100, Medical Center North, Nashville, TN, 37232-2358, USA

    Marat Fudim MD

Authors
  1. Paul A. Sobotka MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David G. Harrison MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marat Fudim MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Paul A. Sobotka 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

Sobotka, P.A., Harrison, D.G., Fudim, M. (2015). The Endpoint on Measuring the Clinical Effects of Renal Denervation: What Are the Best Surrogates. In: Heuser, R., Schlaich, M., Sievert, H. (eds) Renal Denervation. Springer, London. https://doi.org/10.1007/978-1-4471-5223-1_4

Download citation

  • DOI: https://doi.org/10.1007/978-1-4471-5223-1_4

  • 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