Cardiovascular Autonomic Dysfunction in Chronic Kidney Disease: a Comprehensive Review

Current Hypertension Reports

Volumn 17, Issue 8, 2015, Pages

  Salman, Ibrahim M ^a  

^a MACQUARIE UNIVERSITY   (Australia)

Author keywords

Autonomic dysfunction; Cardiovascular disease; Chronic kidney disease; Hypertension; Sympathetic nerve activity; Vagal tone

Indexed keywords

ALISKIREN; AMINE OXIDASE (FLAVIN CONTAINING); AMLODIPINE; ANGIOTENSIN RECEPTOR ANTAGONIST; ATRIAL NATRIURETIC FACTOR; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; ENALAPRIL; ENDOTHELIN; EPROSARTAN; INSULIN; MOXONIDINE; NITRIC OXIDE; RENALASE; SODIUM CHLORIDE; UNCLASSIFIED DRUG; NORADRENALIN;

AUTONOMIC DYSFUNCTION; CARDIOVASCULAR AUTONOMIC DYSFUNCTION; CARDIOVASCULAR DISEASE; CAROTID BARORECEPTOR STIMULATION; CHRONIC KIDNEY DISEASE; CHRONIC KIDNEY FAILURE; COMORBIDITY; DISEASE ASSOCIATION; DISEASE PREDISPOSITION; DRUG EFFECT; END STAGE RENAL DISEASE; GLOMERULUS FILTRATION RATE; HEART VENTRICLE REMODELING; HUMAN; HYPERTENSION; INVASIVE PROCEDURE; KIDNEY DENERVATION; MENTAL STRESS; NEUROMODULATION; NONHUMAN; PARASYMPATHETIC TONE; PROGNOSIS; PROTEIN EXPRESSION; REFLEX DISORDER; RENAL REPLACEMENT THERAPY; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; REVIEW; SEX DIFFERENCE; SURVIVAL RATE; SYMPATHETIC TONE; THERAPY EFFECT; ANIMAL; AUTONOMIC NERVOUS SYSTEM; COMPARATIVE STUDY; PATHOPHYSIOLOGY; SEXUAL DEVELOPMENT;

ANIMALS; AUTONOMIC NERVOUS SYSTEM; CARDIOVASCULAR DISEASES; HUMANS; NOREPINEPHRINE; RENAL INSUFFICIENCY, CHRONIC; RENIN-ANGIOTENSIN SYSTEM; SEX CHARACTERISTICS;

EID: 84931267381     PISSN: 15226417     EISSN: 15343111     Source Type: Journal    
DOI: 10.1007/s11906-015-0571-z     Document Type: Review

References (224)

1. Couser WG, Remuzzi G, Mendis S, Tonelli M. The contribution of chronic kidney disease to the global burden of major noncommunicable diseases. Kidney Int. 2011;80(12):1258–70. doi:10.1038/ki.2011.368.
2. Collins AJ, Foley RN, Gilbertson DT, Chen SC. The state of chronic kidney disease, ESRD, and morbidity and mortality in the first year of dialysis. Clin J Am Soc Nephrol CJASN. 2009;4 Suppl 1:S5–11. doi:10.2215/cjn.05980809.
3. Tonelli M, Wiebe N, Culleton B, House A, Rabbat C, Fok M, et al. Chronic kidney disease and mortality risk: a systematic review. J Am Soc Nephrol. 2006;17(7):2034–47. doi:10.1681/asn.2005101085.
4. U.S. renal data system. U.S. renal data system annual data report: atlas of chronic kidney disease and end-stage renal disease in the United States. National institutes of health, national institute of diabetes and digestive and kidney diseases, Bethesda, MD2013 Jan. Report No.: 1523–6838 (Electronic) 0272–6386 (Linking).
5. Schiffrin EL, Lipman ML, Mann JF. Chronic kidney disease: effects on the cardiovascular system. Circulation. 2007;116(1):85–97. doi:10.1161/circulationaha.106.678342.
6. Kidney disease outcomes quality initiative (KDOQI) clinical practice guideline for chronic kidney disease care [database on the Internet]. National kidney foundation http://www.kidney.org/. 2013. Accessed.
7. Wuhl E, Schaefer F. Managing kidney disease with blood-pressure control. Nat Rev Nephrol. 2011;7(8):434–44. doi:10.1038/nrneph.2011.73.
8. Morgado E, Neves PL. Hypertension and chronic kidney disease: cause and consequence—therapeutic considerations. In: Babaei H, editor. Antihypertensive drugs. Rijeka: InTech; 2012.
9. Neumann J, Ligtenberg G, Klein IH, Boer P, Oey PL, Koomans HA, et al. Sympathetic hyperactivity in hypertensive chronic kidney disease patients is reduced during standard treatment. Hypertension. 2007;49(3):506–10. doi:10.1161/01.HYP.0000256530.39695.a3.
10. Yao Y, Hildreth CM, Farnham MM, Saha M, Sun QJ, Pilowsky PM, et al. The effect of losartan on differential reflex control of sympathetic nerve activity in chronic kidney disease. J Hypertens. 2015. doi:10.1097/hjh.0000000000000535. This recent observational study assessed the role of the renin–angiotensin system in triggering differential reflex sympathetic responses in a rat model of CKD.
11. Ameer OZ, Hildreth CM, Phillips JK. Sympathetic overactivity prevails over the vascular amplifier phenomena in a chronic kidney disease rat model of hypertension. Physiol Rep 2014;2(11). doi:10.14814/phy2.12205.
12. Grassi G, Quarti-Trevano F, Seravalle G, Arenare F, Volpe M, Furiani S, et al. Early sympathetic activation in the initial clinical stages of chronic renal failure. Hypertension. 2011;57(4):846–51. This well-executed clinical study demonstrated increases in SNA during the early stages of renal disease that contribute to further decline in GFR in patients with CKD.
13. Salman IM, Hildreth CM, Ameer OZ, Phillips JK. Differential contribution of afferent and central pathways to the development of baroreflex dysfunction in chronic kidney disease. Hypertension. 2014;63(4):804–10. doi:10.1161/hypertensionaha.113.02110. This was the first study to provide a comprehensive investigation of mechanisms of altered baroreflex function in a rat model of CKD.
14. Hildreth CM, Kandukuri DS, Goodchild AK, Phillips JK. Temporal development of baroreceptor dysfunction in a rodent model of chronic kidney disease. Clin Exp Pharmacol Physiol. 2013;40(7):458–65.
15. Robinson TG, Carr SJ. Cardiovascular autonomic dysfunction in uremia. Kidney Int. 2002;62(6):1921–32.
16. Oparil S, Zaman MA, Calhoun DA. Pathogenesis of hypertension. Ann Intern Med. 2003;139(9):761–76.
17. Ameer OZ, Salman IM, Avolio AP, Phillips JK, Butlin M. Opposing changes in thoracic and abdominal aortic biomechanical properties in rodent models of vascular calcification and hypertension. Am J Physiol Heart Circ Physiol. 2014. doi:10.1152/ajpheart.00139.2014.
18. Passauer J, Pistrosch F, Bussemaker E, Lassig G, Herbrig K, Gross P. Reduced agonist-induced endothelium-dependent vasodilation in uremia is attributable to an impairment of vascular nitric oxide. J Am Soc Nephrol. 2005;16(4):959–65. doi:10.1681/asn.2004070582.
19. Hildreth CM. Prognostic indicators of cardiovascular risk in renal disease. Front Physiol. 2011;2:121. doi:10.3389/fphys.2011.00121.
20. Pal GK, Pal P, Nanda N, Amudharaj D, Adithan C. Cardiovascular dysfunctions and sympathovagal imbalance in hypertension and prehypertension: physiological perspectives. Futur Cardiol. 2013;9(1):53–69. doi:10.2217/fca.12.80.
21. Dursun B, Demircioglu F, Varan HI, Basarici I, Kabukcu M, Ersoy F, et al. Effects of different dialysis modalities on cardiac autonomic dysfunctions in end-stage renal disease patients: one year prospective study. Ren Fail. 2004;26(1):35–8. This prospective clinical study not only demonstrated cardiac autonomic dysfunction in ESRD patients but also showed that continuous ambulatory peritoneal dialysis had a better effect on cardiac autonomic indices than hemodialysis.
22. Ranpuria R, Hall M, Chan CT, Unruh M. Heart rate variability (HRV) in kidney failure: measurement and consequences of reduced HRV. Nephrol Dial Transplant. 2008;23(2):444–9.
23. Shamseddin MK, Parfrey PS. Sudden cardiac death in chronic kidney disease: epidemiology and prevention. Nat Rev Nephrol. 2011;7(3):145–54. doi:10.1038/nrneph.2010.191.
24. Johansson M, Gao SA, Friberg P, Annerstedt M, Carlstrom J, Ivarsson T, et al. Baroreflex effectiveness index and baroreflex sensitivity predict all-cause mortality and sudden death in hypertensive patients with chronic renal failure. J Hypertens. 2007;25(1):163–8.
25. Zoccali C, Mallamaci F, Tripepi G, Parlongo S, Cutrupi S, Benedetto FA, et al. Norepinephrine and concentric hypertrophy in patients with end-stage renal disease. Hypertension. 2002;40(1):41–6.
26. Converse Jr RL, Jacobsen TN, Toto RD, Jost CM, Cosentino F, Fouad-Tarazi F, et al. Sympathetic overactivity in patients with chronic renal failure. N Engl J Med. 1992;327(27):1912–8.
27. Campese VM, Krol E. Neurogenic factors in renal hypertension. Curr Hypertens Rep. 2002;4(3):256–60.
28. Koomans HA, Blankestijn PJ, Joles JA. Sympathetic hyperactivity in chronic renal failure: a wake-up call. J Am Soc Nephrol. 2004;15(3):524–37.
29. Neahring JC, Jones SY, DiBona GF. Cardiopulmonary baroreflex function in nephrotic rats. J Am Soc Nephrol. 1995;5(12):2082–6.
30. Rassaf T, Schueller P, Westenfeld R, Floege J, Eickholt C, Hennersdorf M, et al. Peripheral chemosensor function is blunted in moderate to severe chronic kidney disease. Int J Cardiol. 2012;155(2):201–5.
31. Tinucci T, Abrahao SB, Santello JL, Mion Jr D. Mild chronic renal insufficiency induces sympathetic overactivity. J Hum Hypertens. 2001;15(6):401–6.
32. Gattone 2nd 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 (Maywood, NJ). 2008;233(8):952–7. doi:10.3181/0802-rm-54.
33. 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(7):1250–7.
34. 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(3):2214–20. doi:10.1016/j.ijcard.2013.01.218. This unique clinical study showed reductions in both BP and muscle SNA in renally denervated hypertensive patients with ESRD.
35. Yildiz A, Sever MS, Demirel S, Akkaya V, Turk S, Turkmen A, et al. Improvement of uremic autonomic dysfunction after renal transplantation: a heart rate variability study. Nephron. 1998;80(1):57–60.
36. Harris DC, Rangan GK. Retardation of kidney failure—applying principles to practice. Ann Acad Med Singap. 2005;34(1):16–23.
37. Klein IH, Ligtenberg G, Oey PL, Koomans HA, Blankestijn PJ. Enalapril and losartan reduce sympathetic hyperactivity in patients with chronic renal failure. J Am Soc Nephrol. 2003;14(2):425–30.
38. Herzog CA. Cardiac arrest in dialysis patients: approaches to alter an abysmal outcome. Kidney Int Suppl. 2003;84(200):S197–200.
39. Kashihara N, Satoh M. Molecular pathogenesis of chronic kidney disease. Nihon Rinsho Jpn J Clin Med. 2008;66(9):1671–7.
40. 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 Off J Jpn Soc Hypertens. 2010;33(6):521–8. doi:10.1038/hr.2010.35.
41. Jeewandara TM, Ameer OZ, Boyd R, Wyse BF, Underwood CF, Phillips JK. Protective cardiorenal effects of spironolactone in a rodent model of polycystic kidney disease. Clin Exp Pharmacol Physiol. 2015;42(4):353–60. doi:10.1111/1440-1681.12372.
42. Li Y-L. Cardiovascular autonomic dysfunction in diabetes as a complication: cellular and molecular mechanisms. In: Wagner D, editor. Type 1 diabetes complication. Rijeka: InTech; 2011.
43. Rubinger D, Backenroth R, Sapoznikov D. Restoration of baroreflex function in patients with end-stage renal disease after renal transplantation. Nephrol Dial Transplant. 2009;24(4):1305–13. doi:10.1093/ndt/gfn732.
44. Thayer JF, Yamamoto SS, Brosschot JF. The relationship of autonomic imbalance, heart rate variability and cardiovascular disease risk factors. Int J Cardiol. 2010;141(2):122–31. doi:10.1016/j.ijcard.2009.09.543.
45. Schlaich MP, Socratous F, Hennebry S, Eikelis N, Lambert EA, Straznicky N, et al. Sympathetic activation in chronic renal failure. J Am Soc Nephrol. 2009;20(5):933–9. This excellent review summarizes the deleterious effects of SNS hyperactivity in CKD, as well as its possible underlying mechanisms.
46. Schohn D, Weidmann P, Jahn H, Beretta-Piccoli C. Norepinephrine-related mechanism in hypertension accompanying renal failure. Kidney Int. 1985;28(5):814–22.
47. Levitan D, Massry SG, Romoff M, Campese VM. Plasma catecholamines and autonomic nervous system function in patients with early renal insufficiency and hypertension: effect of clonidine. Nephron. 1984;36(1):24–9.
48. Phillips JK, Hopwood D, Loxley RA, Ghatora K, Coombes JD, Tan YS, et al. Temporal relationship between renal cyst development, hypertension and cardiac hypertrophy in a new rat model of autosomal recessive polycystic kidney disease. Kidney Blood Press Res. 2007;30(3):129–44.
49. Ligtenberg G, Blankestijn PJ, Oey PL, Klein IH, Dijkhorst-Oei LT, Boomsma F, et al. Reduction of sympathetic hyperactivity by enalapril in patients with chronic renal failure. N Engl J Med. 1999;340(17):1321–8. This clinical study was one of the first to assess sympathetic baroreflex function in CKD patients.
50. Park J, Campese VM, Nobakht N, Middlekauff HR. Differential distribution of muscle and skin sympathetic nerve activity in patients with end-stage renal disease. J Appl Physiol (Bethesda, Md: 1985). 2008;105(6):1873–6. doi:10.1152/japplphysiol.90849.2008.
51. Bruno RM, Ghiadoni L, Seravalle G, Dell'oro R, Taddei S, Grassi G. Sympathetic regulation of vascular function in health and disease. Front Physiol. 2012;3:284. doi:10.3389/fphys.2012.00284.
52. Sahin M, Kayatas M, Urun Y, Sennaroglu E, Akdur S. Performing only one cardiovascular reflex test has a high positive predictive value for diagnosing autonomic neuropathy in patients with chronic renal failure on hemodialysis. Ren Fail. 2006;28(5):383–7. doi:10.1080/08860220600683722.
53. Lewanski R, Chrzanowski W. Assessment of autonomic nervous system by spectral analysis of heart rate and blood pressure in hemodialysed patients. Pol Merkur Lekarski Org Polskiego Towarz Lekarskiego. 2003;15(88):391–3.
54. Badve SV, Roberts MA, Hawley CM, Cass A, Garg AX, Krum H, et al. Effects of beta-adrenergic antagonists in patients with chronic kidney disease: a systematic review and meta-analysis. J Am Coll Cardiol. 2011;58(11):1152–61. doi:10.1016/j.jacc.2011.04.041.
55. Grassi G, Seravalle G, Ghiadoni L, Tripepi G, Bruno RM, Mancia G, et al. Sympathetic nerve traffic and asymmetric dimethylarginine in chronic kidney disease. Clin J Am Soc Nephrol CJASN. 2011;6(11):2620–7. doi:10.2215/cjn.06970711.
56. Adamczak M, Zeier M, Dikow R, Ritz E. Kidney and hypertension. Kidney Int Suppl. 2002;80:62–7.
57. Erami C, Zhang H, Ho JG, French DM, Faber JE. Alpha(1)-adrenoceptor stimulation directly induces growth of vascular wall in vivo. Am J Physiol Heart Circ Physiol. 2002;283(4):H1577–87. doi:10.1152/ajpheart.00218.2002.
58. Zhang H, Faber JE. Trophic effect of norepinephrine on arterial intima-media and adventitia is augmented by injury and mediated by different alpha1-adrenoceptor subtypes. Circ Res. 2001;89(9):815–22.
59. Raizada V, Hillerson D, Amaram JS, Skipper B. Angiotensin II-mediated left ventricular abnormalities in chronic kidney disease. J Investig Med Off Publ Am Fed Clin Res. 2012;60(5):785–91. doi:10.231/JIM.0b013e318250b101.
60. Grisk O, Rettig R. Interactions between the sympathetic nervous system and the kidneys in arterial hypertension. Cardiovasc Res. 2004;61(2):238–46.
61. Schlaich MP, Kaye DM, Lambert E, Sommerville M, Socratous F, Esler MD. Relation between cardiac sympathetic activity and hypertensive left ventricular hypertrophy. Circulation. 2003;108(5):560–5. doi:10.1161/01.cir.0000081775.72651.b6.
62. Guizar-Mendoza JM, Amador-Licona N, Lozada EE, Rodriguez L, Gutierrez-Navarro M, Dubey-Ortega LA, et al. Left ventricular mass and heart sympathetic activity after renal transplantation in children and young adults. Pediatr Nephrol. 2006;21(10):1413–8. doi:10.1007/s00467-006-0238-8.
63. Mircoli L, Rivera R, Bonforte G, Fedele L, Genovesi S, Surian M, et al. Influence of left ventricular mass, uremia and hypertension on vagal tachycardic reserve. J Hypertens. 2003;21(8):1547–53. doi:10.1097/01.hjh.0000084720.53355.ad.
64. Tory K, Horvath E, Suveges Z, Fekete A, Sallay P, Berta K, et al. Effect of propranolol on heart rate variability in patients with end-stage renal disease: a double-blind, placebo-controlled, randomized crossover pilot trial. Clin Nephrol. 2004;61(5):316–23.
65. Agarwal A, Anand IS, Sakhuja V, Chugh KS. Effect of dialysis and renal transplantation on autonomic dysfunction in chronic renal failure. Kidney Int. 1991;40(3):489–95.
66. de Ferrari GM, Vanoli E, Stramba-Badiale M, Hull Jr SS, Foreman RD, Schwartz PJ. Vagal reflexes and survival during acute myocardial ischemia in conscious dogs with healed myocardial infarction. Am J Physiol. 1991;261(1 Pt 2):H63–9.
67. Di Rienzo M, Parati G, Castiglioni P, Tordi R, Mancia G, Pedotti A. Baroreflex effectiveness index: an additional measure of baroreflex control of heart rate in daily life. Am J Physiol Regul Integr Comp Physiol. 2001;280(3):R744–51.
68. Johnson PL, Shekhar A. Panic-prone state induced in rats with GABA dysfunction in the dorsomedial hypothalamus is mediated by NMDA receptors. J Neurosci Off J Soc Neurosci. 2006;26(26):7093–104. doi:10.1523/jneurosci.0408-06.2006.
69. Lacy P, Carr SJ, O'Brien D, Fentum B, Williams B, Paul SK, et al. Reduced glomerular filtration rate in pre-dialysis non-diabetic chronic kidney disease patients is associated with impaired baroreceptor sensitivity and reduced vascular compliance. Clin Sci (London, England: 1979). 2006;110(1):101–8. doi:10.1042/cs20050192.
70. Studinger P, Lenard Z, Mersich B, Reusz GS, Kollai M. Determinants of baroreflex function in juvenile end-stage renal disease. Kidney Int. 2006;69(12):2236–42. doi:10.1038/sj.ki.5000307.
71. Salman IM, Phillips JK, Ameer OZ, Hildreth CM. Abnormal central control underlies impaired baroreflex control of heart rate and sympathetic nerve activity in female Lewis polycystic kidney rats. J Hypertens. 2015. This was the first observational study to provide a mechanistic explanation for baroreflex dysfunction in a female rat model of CKD.
72. Merrill DC, Segar JL, McWeeny OJ, Robillard JE. Sympathetic responses to cardiopulmonary vagal afferent stimulation during development. Am J Physiol. 1999;277(4 Pt 2):H1311–6.
73. Frank H, Heusser K, Hoffken B, Huber P, Schmieder RE, Schobel HP. Effect of erythropoietin on cardiovascular prognosis parameters in hemodialysis patients. Kidney Int. 2004;66(2):832–40. doi:10.1111/j.1523-1755.2004.00810.x.
74. Grassi G, Parati G, Pomidossi G, Giannattasio C, Casadei R, Bolla GB, et al. Effects of haemodialysis and kidney transplantation on carotid and cardiopulmonary baroreflexes in uremic patients. J Hypertens. 1987;5 suppl 5:S367–9.
75. Hinojosa-Laborde C, Jones SY, DiBona GF. Hemodynamics and baroreflex function in rats with nephrotic syndrome. Am J Physiol. 1994;267(4 Pt 2):R953–64.
76. Daugirdas JT. Pathophysiology of dialysis hypotension: an update. Am J Kidney Dis. 2001;38(4 Suppl 4):S11–7.
77. Rassaf T, Westenfeld R, Balzer J, Lauer T, Merx M, Floege J, et al. Modulation of peripheral chemoreflex by neurohumoral adaptations after kidney transplantation. Eur J Med Res. 2010;15 Suppl 2:83–7.
78. Despas F, Detis N, Dumonteil N, Labrunee M, Bellon B, Franchitto N, et al. Excessive sympathetic activation in heart failure with chronic renal failure: role of chemoreflex activation. J Hypertens. 2009;27(9):1849–54. doi:10.1097/HJH.0b013e32832e8d0f.
79. Kotanko P. Cause and consequences of sympathetic hyperactivity in chronic kidney disease. Blood Purif. 2006;24(1):95–9. doi:10.1159/000089444.
80. Grassi G. Renin-angiotensin-sympathetic crosstalks in hypertension: reappraising the relevance of peripheral interactions. J Hypertens. 2001;19(10):1713–6.
81. Reid IA. Interactions between ANG II, sympathetic nervous system, and baroreceptor reflexes in regulation of blood pressure. Am J Physiol. 1992;262:E763–78.
82. Gao L, Wang WZ, Wang W, Zucker IH. Imbalance of angiotensin type 1 receptor and angiotensin II type 2 receptor in the rostral ventrolateral medulla: potential mechanism for sympathetic overactivity in heart failure. Hypertension. 2008;52(4):708–14. doi:10.1161/hypertensionaha.108.116228.
83. Zucker IH. Novel mechanisms of sympathetic regulation in chronic heart failure. Hypertension. 2006;48(6):1005–11. doi:10.1161/01.hyp.0000246614.47231.25.
84. Barajas L, Wang P. Myelinated nerves of the rat kidney. A light and electron microscopic autoradiographic study. J Ultrastruct Res. 1978;65(2):148–62.
85. Recordati G, Moss NG, Genovesi S, Rogenes P. Renal chemoreceptors. J Auton Nerv Syst. 1981;3(2–4):237–51.
86. Donovan MK, Wyss JM, Winternitz SR. Localization of renal sensory neurons using the fluorescent dye technique. Brain Res. 1983;259(1):119–22.
87. Solano-Flores LP, Rosas-Arellano MP, Ciriello J. Fos induction in central structures after afferent renal nerve stimulation. Brain Res. 1997;753(1):102–19.
88. Johns EJ, Kopp UC, DiBona GF. Neural control of renal function. Compr Physiol. 2011;1(2):731–67. doi:10.1002/cphy.c100043.
89. Campese VM, Kogosov E, Koss M. Renal afferent denervation prevents the progression of renal disease in the renal ablation model of chronic renal failure in the rat. Am J Kidney Dis. 1995;26(5):861–5.
90. Hausberg M, Kosch M, Harmelink P, Barenbrock M, Hohage H, Kisters K, et al. Sympathetic nerve activity in end-stage renal disease. Circulation. 2002;106(15):1974–9. This fascinating clinical study demonstrated increased SNA despite correction of uremia in renal transplant recipients with diseased native kidneys, indicating a possible role for renal afferents in triggering heightened efferent sympathetic discharge.
91. Ye S, Ozgur B, Campese VM. Renal afferent impulses, the posterior hypothalamus, and hypertension in rats with chronic renal failure. Kidney Int. 1997;51(3):722–7.
92. Ye S, Gamburd M, Mozayeni P, Koss M, Campese VM. A limited renal injury may cause a permanent form of neurogenic hypertension. Am J Hypertens. 1998;11(6 Pt 1):723–8.
93. Katholi RE, Whitlow PL, Winternitz SR, Oparil S. Importance of the renal nerves in established two-kidney, one clip Goldblatt hypertension. Hypertension. 1982;4(3 Pt 2):166–74.
94. Miyajima E, Yamada Y, Yoshida Y, Matsukawa T, Shionoiri H, Tochikubo O, et al. Muscle sympathetic nerve activity in renovascular hypertension and primary aldosteronism. Hypertension. 1991;17(6 Pt 2):1057–62.
95. Fall PJ, Prisant LM. Polycystic kidney disease. J Clin Hypertens (Greenwich, Conn). 2005;7(10):617–9. 25.
96. Costa F, Diedrich A, Johnson B, Sulur P, Farley G, Biaggioni I. Adenosine, a metabolic trigger of the exercise pressor reflex in humans. Hypertension. 2001;37(3):917–22.
97. Chesterton LJ, Sigrist MK, Bennett T, Taal MW, McIntyre CW. Reduced baroreflex sensitivity is associated with increased vascular calcification and arterial stiffness. Nephrol Dial Transplant. 2005;20(6):1140–7.
98. Temmar M, Liabeuf S, Renard C, Czernichow S, Esper NE, Shahapuni I, et al. Pulse wave velocity and vascular calcification at different stages of chronic kidney disease. J Hypertens. 2010;28(1):163–9. doi:10.1097/HJH.0b013e328331b81e.
99. Ng K, Hildreth CM, Phillips JK, Avolio AP. Aortic stiffness is associated with vascular calcification and remodeling in a chronic kidney disease rat model. Am J Physiol Renal Physiol. 2011;300(6):6.
100. Pai A, Leaf EM, El-Abbadi M, Giachelli CM. Elastin degradation and vascular smooth muscle cell phenotype change precede cell loss and arterial medial calcification in a uremic mouse model of chronic kidney disease. Am J Pathol. 2011;178(2):764–73.
101. Chan CT, Jain V, Picton P, Pierratos A, Floras JS. Nocturnal hemodialysis increases arterial baroreflex sensitivity and compliance and normalizes blood pressure of hypertensive patients with end-stage renal disease. Kidney Int. 2005;68(1):338–44. doi:10.1111/j.1523-1755.2005.00411.x.
102. Kosch M, Barenbrock M, Kisters K, Rahn KH, Hausberg M. Relationship between muscle sympathetic nerve activity and large artery mechanical vessel wall properties in renal transplant patients. J Hypertens. 2002;20(3):501–8.
103. Diwan V, Gobe G, Brown L. Glibenclamide improves kidney and heart structure and function in the adenine-diet model of chronic kidney disease. Pharmacol Res Off J Ital Pharmacol Soc. 2014;79:104–10. doi:10.1016/j.phrs.2013.11.007.
104. Fedecostante M, Spannella F, Cola G, Espinosa E, Dessi-Fulgheri P, Sarzani R. Chronic kidney disease is characterized by “double trouble” higher pulse pressure plus night-time systolic blood pressure and more severe cardiac damage. PLoS One. 2014;9(1), e86155. doi:10.1371/journal.pone.0086155.
105. Wang AY, Li PK, Lui SF, Sanderson JE. Angiotensin converting enzyme inhibition for cardiac hypertrophy in patients with end-stage renal disease: what is the evidence? Nephrology (Carlton, Vic). 2004;9(4):190–7. doi:10.1111/j.1440-1797.2004.00260.x.
106. Edwards NC, Steeds RP, Stewart PM, Ferro CJ, Townend JN. Effect of spironolactone on left ventricular mass and aortic stiffness in early-stage chronic kidney disease: a randomized controlled trial. J Am Coll Cardiol. 2009;54(6):505–12. doi:10.1016/j.jacc.2009.03.066.
107. Moody WE, Edwards NC, Chue CD, Ferro CJ, Townend JN. Arterial disease in chronic kidney disease. Heart. 2013;99(6):365–72. doi:10.1136/heartjnl-2012-302818.
108. Grassi G, Giannattasio C, Cleroux J, Cuspidi C, Sampieri L, Bolla GB, et al. Cardiopulmonary reflex before and after regression of left ventricular hypertrophy in essential hypertension. Hypertension. 1988;12(3):227–37.
109. Uggere TA, Abreu GR, Sampaio KN, Cabral AM, Bissoli NS. The cardiopulmonary reflexes of spontaneously hypertensive rats are normalized after regression of left ventricular hypertrophy and hypertension. Braz J Med Biol Res Rev Bras Pesqui Med Biol Soc Bras Biofisica [et al]. 2000;33(5):589–94.
110. Furchgott RF, Jothianandan D. Endothelium-dependent and -independent vasodilation involving cyclic GMP: relaxation induced by nitric oxide, carbon monoxide and light. Blood Vessels. 1991;28(1–3):52–61.
111. Hirooka Y, Kishi T, Sakai K, Takeshita A, Sunagawa K. Imbalance of central nitric oxide and reactive oxygen species in the regulation of sympathetic activity and neural mechanisms of hypertension. Am J Physiol Regul Integr Comp Physiol. 2011;300(4):R818–26. doi:10.1152/ajpregu.00426.2010.
112. Nurminen ML, Ylikorkala A, Vapaatalo H. Central inhibition of nitric oxide synthesis increases blood pressure and heart rate in anesthetized rats. Methods Find Exp Clin Pharmacol. 1997;19(1):35–41.
113. Sakuma I, Togashi H, Yoshioka M, Saito H, Yanagida M, Tamura M, et al. NG-methyl-L-arginine, an inhibitor of L-arginine-derived nitric oxide synthesis, stimulates renal sympathetic nerve activity in vivo. A role for nitric oxide in the central regulation of sympathetic tone? Circ Res. 1992;70(3):607–11.
114. Cunha RS, Cabral AM, Vasquez EC. Evidence that the autonomic nervous system plays a major role in the L-NAME-induced hypertension in conscious rats. Am J Hypertens. 1993;6(9):806–9.
115. Sander M, Hansen PG, Victor RG. Sympathetically mediated hypertension caused by chronic inhibition of nitric oxide. Hypertension. 1995;26(4):691–5.
116. Harada S, Tokunaga S, Momohara M, Masaki H, Tagawa T, Imaizumi T, et al. Inhibition of nitric oxide formation in the nucleus tractus solitarius increases renal sympathetic nerve activity in rabbits. Circ Res. 1993;72(3):511–6.
117. Zanzinger J, Czachurski J, Seller H. Inhibition of basal and reflex-mediated sympathetic activity in the RVLM by nitric oxide. Am J Physiol. 1995;268(4 Pt 2):R958–62.
118. Zhang K, Mayhan WG, Patel KP. Nitric oxide within the paraventricular nucleus mediates changes in renal sympathetic nerve activity. Am J Physiol. 1997;273(3 Pt 2):R864–72.
119. Spieker LE, Corti R, Binggeli C, Luscher TF, Noll G. Baroreceptor dysfunction induced by nitric oxide synthase inhibition in humans. J Am Coll Cardiol. 2000;36(1):213–8.
120. Endemann DH, Schiffrin EL. Endothelial dysfunction. J Am Soc Nephrol. 2004;15(8):1983–92. doi:10.1097/01.asn.0000132474.50966.da.
121. Schmidt RJ, Baylis C. Total nitric oxide production is low in patients with chronic renal disease. Kidney Int. 2000;58(3):1261–6. doi:10.1046/j.1523-1755.2000.00281.x.
122. Shinohara K, Hirooka Y, Kishi T, Sunagawa K. Reduction of nitric oxide-mediated gamma-amino butyric acid release in rostral ventrolateral medulla is involved in superoxide-induced sympathoexcitation of hypertensive rats. Circ J. 2012;76(12):2814–21.
123. Ye S, Nosrati S, Campese VM. Nitric oxide (NO) modulates the neurogenic control of blood pressure in rats with chronic renal failure (CRF). J Clin Investig. 1997;99(3):540–8. doi:10.1172/jci119191.
124. Montezano AC, Touyz RM. Oxidative stress, Noxs, and hypertension: experimental evidence and clinical controversies. Ann Med. 2012;44 Suppl 1:S2–16. doi:10.3109/07853890.2011.653393.
125. Matthews KA, Woodall KL, Allen MT. Cardiovascular reactivity to stress predicts future blood pressure status. Hypertension. 1993;22(4):479–85.
126. Schuler JL, O'Brien WH. Cardiovascular recovery from stress and hypertension risk factors: a meta-analytic review. Psychophysiology. 1997;34(6):649–59.
127. Chandola T, Britton A, Brunner E, Hemingway H, Malik M, Kumari M, et al. Work stress and coronary heart disease: what are the mechanisms? Eur Heart J. 2008;29(5):640–8. doi:10.1093/eurheartj/ehm584.
128. Niebylski A, Boccolini A, Bensi N, Binotti S, Hansen C, Yaciuk R, et al. Neuroendocrine changes and natriuresis in response to social stress in rats. Stress Health J Int Soc Investig Stress. 2012;28(3):179–85. doi:10.1002/smi.1411.
129. Wallin BG, Esler M, Dorward P, Eisenhofer G, Ferrier C, Westerman R, et al. Simultaneous measurements of cardiac noradrenaline spillover and sympathetic outflow to skeletal muscle in humans. J Physiol. 1992;453:45–58.
130. Black PH. Stress and the inflammatory response: a review of neurogenic inflammation. Brain Behav Immun. 2002;16(6):622–53.
131. Kouidi E, Karagiannis V, Grekas D, Iakovides A, Kaprinis G, Tourkantonis A, et al. Depression, heart rate variability, and exercise training in dialysis patients. Eur J Cardiovasc Prev Rehabil Off J Eur Soc Cardiol Work Groups Epidemiol Prev Card Rehabil Exerc Physiol. 2010;17(2):160–7. doi:10.1097/HJR.0b013e32833188c4.
132. Palkovits M, Sebekova K, Klenovics KS, Kebis A, Fazeli G, Bahner U, et al. Neuronal activation in the central nervous system of rats in the initial stage of chronic kidney disease-modulatory effects of losartan and moxonidine. PLoS One. 2013;8(6), e66543. doi:10.1371/journal.pone.0066543.
133. Sit D, Kadiroglu AK, Kayabasi H, Yilmaz ME. The prevalence of insulin resistance in nondiabetic nonobese patients with chronic kidney disease. Adv Ther. 2006;23(6):988–98.
134. Svensson M, Eriksson JW. Insulin resistance in diabetic nephropathy—cause or consequence? Diabetes Metab Res Rev. 2006;22(5):401–10. doi:10.1002/dmrr.648.
135. Hall JE, Brands MW, Zappe DH, Alonso Galicia M. Insulin resistance, hyperinsulinemia, and hypertension: causes, consequences, or merely correlations? Proc Soc Exp Biol Med Soc Exp Biol Med (New York, NY). 1995;208(4):317–29.
136. Ryan JP, Sheu LK, Verstynen TD, Onyewuenyi IC, Gianaros PJ. Cerebral blood flow links insulin resistance and baroreflex sensitivity. PLoS One. 2013;8(12), e83288. doi:10.1371/journal.pone.0083288.
137. Schneider MP, Mann JF. Endothelin antagonism for patients with chronic kidney disease: still a hope for the future. Nephrol Dial Transplant. 2014;29 Suppl 1:i69–73. doi:10.1093/ndt/gft339.
138. Shichiri M, Hirata Y, Ando K, Emori T, Ohta K, Kimoto S, et al. Plasma endothelin levels in hypertension and chronic renal failure. Hypertension. 1990;15(5):493–6.
139. Gulati A, Rebello S, Kumar A. Role of sympathetic nervous system in cardiovascular effects of centrally administered endothelin-1 in rats. Am J Physiol. 1997;273(3 Pt 2):H1177–86.
140. Nakamura K, Sasaki S, Moriguchi J, Morimoto S, Miki S, Kawa T, et al. Central effects of endothelin and its antagonists on sympathetic and cardiovascular regulation in SHR-SP. J Cardiovasc Pharmacol. 1999;33(6):876–82.
141. Mortensen LH. Endothelin and the central and peripheral nervous systems: a decade of endothelin research. Clin Exp Pharmacol Physiol. 1999;26(12):980–4.
142. Smirnov AV, Petrishchev NN, Panina I, Mnuskina MM, Achkasova VV, Rumiantsev A, et al. The level of endothelin-1 and reactivity of skin microvessels in patients with early stages of chronic kidney disease. Ter Arkh. 2011;83(6):13–8.
143. Xu J, Li G, Wang P, Velazquez H, Yao X, Li Y, et al. Renalase is a novel, soluble monoamine oxidase that regulates cardiac function and blood pressure. J Clin Invest. 2005;115(5):1275–80. doi:10.1172/jci24066.
144. Desir GV, Peixoto AJ. Renalase in hypertension and kidney disease. Nephrol Dial Transplant. 2014;29(1):22–8. doi:10.1093/ndt/gft083.
145. Li G, Xu J, Wang P, Velazquez H, Li Y, Wu Y, et al. Catecholamines regulate the activity, secretion, and synthesis of renalase. Circulation. 2008;117(10):1277–82. doi:10.1161/circulationaha.107.732032.
146. Gu R, Lu W, Xie J, Bai J, Xu B. Renalase deficiency in heart failure model of rats—a potential mechanism underlying circulating norepinephrine accumulation. PLoS One. 2011;6(1), e14633. doi:10.1371/journal.pone.0014633.
147. Brooks VL, Haywood JR, Johnson AK. Translation of salt retention to central activation of the sympathetic nervous system in hypertension. Clin Exp Pharmacol Physiol. 2005;32(5–6):426–32. doi:10.1111/j.1440-1681.2005.04206.x.
148. Mailloux LU. The overlooked role of salt restriction in dialysis patients. Semin Dial. 2000;13(3):150–1.
149. Meng L, Fu B, Zhang T, Han Z, Yang M. Salt sensitivity of blood pressure in non-dialysis patients with chronic kidney disease. Ren Fail. 2014;36(3):345–50. doi:10.3109/0886022x.2013.866008.
150. Campese VM, Mozayeni P, Ye S, Gumbard M. High salt intake inhibits nitric oxide synthase expression and aggravates hypertension in rats with chronic renal failure. J Nephrol. 2002;15(4):407–13.
151. Fujita M, Ando K, Kawarazaki H, Kawarasaki C, Muraoka K, Ohtsu H, et al. Sympathoexcitation by brain oxidative stress mediates arterial pressure elevation in salt-induced chronic kidney disease. Hypertension. 2012;59(1):105–12. doi:10.1161/hypertensionaha.111.182923.
152. Wambach G, Gotz S, Suckau G, Bonner G, Kaufmann W. Plasma levels of atrial natriuretic peptide are raised in essential hypertension during low and high sodium intake. Klin Wochenschr. 1987;65(5):232–7.
153. Akiba T, Tachibana K, Togashi K, Hiroe M, Marumo F. Plasma human brain natriuretic peptide in chronic renal failure. Clin Nephrol. 1995;44 Suppl 1:S61–4.
154. Peng N, Oparil S, Meng QC, Wyss JM. Atrial natriuretic peptide regulation of noradrenaline release in the anterior hypothalamic area of spontaneously hypertensive rats. J Clin Investig. 1996;98(9):2060–5. doi:10.1172/jci119011.
155. Vatta MS, Papouchado ML, Bianciotti LG, Fernandez BE. Atrial natriuretic factor inhibits noradrenaline release in the presence of angiotensin II and III in the rat hypothalamus. Comp Biochem Physiol C Comp Pharmacol Toxicol. 1993;106(2):545–8.
156. Toader E, McAllen RM, Cividjian A, Woods RL, Quintin L. Effect of systemic B-type natriuretic peptide on cardiac vagal motoneuron activity. Am J Physiol Heart Circ Physiol. 2007;293(6):H3465–70. doi:10.1152/ajpheart.00528.2007.
157. Woods RL, Courneya CA, Head GA. Nonuniform enhancement of baroreflex sensitivity by atrial natriuretic peptide in conscious rats and dogs. Am J Physiol. 1994;267(3 Pt 2):R678–86.
158. Hood SG, Woods RL. Vagal reflex actions of atrial natriuretic peptide survive physiological but not pathological cardiac hypertrophy in rat. Exp Physiol. 2004;89(4):445–54. doi:10.1113/expphysiol.2004.027557.
159. Burt VL, Whelton P, Roccella EJ, Brown C, Cutler JA, Higgins M, et al. Prevalence of hypertension in the US adult population. Results from the third national health and nutrition examination survey, 1988–1991. Hypertension. 1995;25(3):305–13.
160. Maric C. Sex differences in cardiovascular disease and hypertension: involvement of the renin-angiotensin system. Hypertension. 2005;46(3):475–6. doi:10.1161/01.HYP.0000178600.88820.b2.
161. Reckelhoff JF. Gender differences in the regulation of blood pressure. Hypertension. 2001;37(5):1199–208.
162. Hogarth AJ, Mackintosh AF, Mary DA. Gender-related differences in the sympathetic vasoconstrictor drive of normal subjects. Clin Sci. 2007;112(6):353–61.
163. Kim A, Deo SH, Vianna LC, Balanos GM, Hartwich D, Fisher JP, et al. Sex differences in carotid baroreflex control of arterial blood pressure in humans: relative contribution of cardiac output and total vascular conductance. Am J Physiol Heart Circ Physiol. 2011;301(6):H2454–65.
164. Shoemaker JK, Hogeman CS, Khan M, Kimmerly DS, Sinoway LI. Gender affects sympathetic and hemodynamic response to postural stress. Am J Physiol Heart Circ Physiol. 2001;281(5):H2028–35.
165. Tank J, Diedrich A, Szczech E, Luft FC, Jordan J. Baroreflex regulation of heart rate and sympathetic vasomotor tone in women and men. Hypertension. 2005;45(6):1159–64.
166. Brooks VL, Cassaglia PA, Zhao D, Goldman RK. Baroreflex function in females: changes with the reproductive cycle and pregnancy. Gend Med. 2012;9(2):61–7.
167. Abdel-Rahman AR, Merrill RH, Wooles WR. Gender-related differences in the baroreceptor reflex control of heart rate in normotensive humans. J Appl Physiol (Bethesda, Md: 1985). 1994;77(2):606–13.
168. Frey MA, Tomaselli CM, Hoffler WG. Cardiovascular responses to postural changes: differences with age for women and men. J Clin Pharmacol. 1994;34(5):394–402.
169. Convertino VA. Gender differences in autonomic functions associated with blood pressure regulation. Am J Physiol. 1998;275(6 Pt 2):R1909–20.
170. Scislo TJ, DiCarlo SE. Gender difference in cardiopulmonary reflex inhibition of sympathetic nerve activity. Am J Physiol. 1994;267(4 Pt 2):H1537–43.
171. Hunt BE, Taylor JA, Hamner JW, Gagnon M, Lipsitz LA. Estrogen replacement therapy improves baroreflex regulation of vascular sympathetic outflow in postmenopausal women. Circulation. 2001;103(24):2909–14.
172. Fadel PJ, Zhao W, Thomas GD. Impaired vasomodulation is associated with reduced neuronal nitric oxide synthase in skeletal muscle of ovariectomized rats. J Physiol. 2003;549(Pt 1):243–53.
173. Mohamed MK, El-Mas MM, Abdel-Rahman AA. Estrogen enhancement of baroreflex sensitivity is centrally mediated. Am J Physiol. 1999;276(4 Pt 2):R1030–7.
174. Saleh TM, Connell BJ. 17beta-estradiol modulates baroreflex sensitivity and autonomic tone of female rats. J Auton Nerv Syst. 2000;80(3):148–61.
175. Du XJ, Dart AM, Riemersma RA. Sex differences in the parasympathetic nerve control of rat heart. Clin Exp Pharmacol Physiol. 1994;21(6):485–93.
176. Schroeder C, Adams F, Boschmann M, Tank J, Haertter S, Diedrich A, et al. Phenotypical evidence for a gender difference in cardiac norepinephrine transporter function. Am J Physiol Regul Integr Comp Physiol. 2004;286(5):R851–6.
177. Esler M, Jennings G, Lambert G, Meredith I, Horne M, Eisenhofer G. Overflow of catecholamine neurotransmitters to the circulation: source, fate, and functions. Physiol Rev. 1990;70(4):963–85.
178. Reckelhoff JF, Zhang H, Srivastava K. Gender differences in development of hypertension in spontaneously hypertensive rats: role of the renin-angiotensin system. Hypertension. 2000;35(1 Pt 2):480–3.
179. Crofton JT, Ota M, Share L. Role of vasopressin, the renin-angiotensin system and sex in Dahl salt-sensitive hypertension. J Hypertens. 1993;11(10):1031–8.
180. Haywood JR, Hinojosa-Laborde C. Sexual dimorphism of sodium-sensitive renal-wrap hypertension. Hypertension. 1997;30(3 Pt 2):667–71.
181. Xue B, Pamidimukkala J, Hay M. Sex differences in the development of angiotensin II-induced hypertension in conscious mice. Am J Physiol Heart Circ Physiol. 2005;288(5):H2177–84. doi:10.1152/ajpheart.00969.2004.
182. Hogarth AJ, Mackintosh AF, Mary DA. The effect of gender on the sympathetic nerve hyperactivity of essential hypertension. J Hum Hypertens. 2007;21(3):239–45. doi:10.1038/sj.jhh.1002132.
183. Pavithran P, Madanmohan T, Nandeesha H. Sex differences in short-term heart rate variability in patients with newly diagnosed essential hypertension. J Clin Hypertens. 2008;10(12):904–10.
184. Johnson MS, DeMarco VG, Heesch CM, Whaley-Connell AT, Schneider RI, Rehmer NT, et al. Sex differences in baroreflex sensitivity, heart rate variability, and end organ damage in the TGR(mRen2)27 rat. Am J Physiol Heart Circ Physiol. 2011;301(4):H1540–50.
185. Eriksen BO, Ingebretsen OC. The progression of chronic kidney disease: a 10-year population-based study of the effects of gender and age. Kidney Int. 2006;69(2):375–82. doi:10.1038/sj.ki.5000058.
186. Jafar TH, Schmid CH, Stark PC, Toto R, Remuzzi G, Ruggenenti P, et al. The rate of progression of renal disease may not be slower in women compared with men: a patient-level meta-analysis. Nephrol Dial Transplant. 2003;18(10):2047–53. doi:10.1093/ndt/gfg317.
187. Carrero JJ. Gender differences in chronic kidney disease: underpinnings and therapeutic implications. Kidney Blood Press Res. 2010;33(5):383–92. doi:10.1159/000320389.
188. Vink EE, de Jager RL, Blankestijn PJ. Sympathetic hyperactivity in chronic kidney disease: pathophysiology and (new) treatment options. Curr Hypertens Rep. 2013;15(2):95–101. doi:10.1007/s11906-013-0328-5.
189. Weir MR. The renoprotective effects of RAS inhibition: focus on prevention and treatment of chronic kidney disease. Postgrad Med. 2009;121(1):96–103. doi:10.3810/pgm.2009.01.1958.
190. Weir MR. Effects of renin-angiotensin system inhibition on end-organ protection: can we do better? Clin Ther. 2007;29(9):1803–24. doi:10.1016/j.clinthera.2007.09.019.
191. Sato R, Mizuno M, Miura T, Kato Y, Watanabe S, Fuwa D, et al. Angiotensin receptor blockers regulate the synchronization of circadian rhythms in heart rate and blood pressure. J Hypertens. 2013;31(6):1233–8. doi:10.1097/HJH.0b013e32836043c9.
192. Ondocin PT, Narsipur SS. Influence of angiotensin converting enzyme inhibitor treatment on cardiac autonomic modulation in patients receiving haemodialysis. Nephrology (Carlton, Vic). 2006;11(6):497–501. doi:10.1111/j.1440-1797.2006.00680.x.
193. Neumann J, Ligtenberg G, Oey L, Koomans HA, Blankestijn PJ. Moxonidine normalizes sympathetic hyperactivity in patients with eprosartan-treated chronic renal failure. J Am Soc Nephrol. 2004;15(11):2902–7. doi:10.1097/01.asn.0000143471.10750.8c. This clinical study showed that normalized sympathetic nerve discharge in CKD patients can be achieved only with combination therapy comprising a central sympatholytic agent and an ARB.
194. Siddiqi L, Oey PL, Blankestijn PJ. Aliskiren reduces sympathetic nerve activity and blood pressure in chronic kidney disease patients. Nephrol Dial Transplant. 2011;26(9):2930–4. doi:10.1093/ndt/gfq857.
195. Narsipur SS, Srinivasan B, Singh B. Effect of simvastatin use on autonomic function in patients with end stage renal disease. Cardiovasc Hematol Disord Drug Targets. 2011;11(1):53–7.
196. Suzuki H, Moriwaki K, Kanno Y, Nakamoto H, Okada H, Chen XM. Comparison of the effects of an ACE inhibitor and alphabeta blocker on the progression of renal failure with left ventricular hypertrophy: preliminary report. Hypertens Res Off J Jpn Soc Hypertens. 2001;24(2):153–8.
197. Vonend O, Marsalek P, Russ H, Wulkow R, Oberhauser V, Rump LC. Moxonidine treatment of hypertensive patients with advanced renal failure. J Hypertens. 2003;21(9):1709–17. doi:10.1097/01.hjh.0000084733.53355.c3.
198. Amann K, Koch A, Hofstetter J, Gross ML, Haas C, Orth SR, et al. Glomerulosclerosis and progression: effect of subantihypertensive doses of alpha and beta blockers. Kidney Int. 2001;60(4):1309–23. doi:10.1046/j.1523-1755.2001.00936.x.
199. Amann K, Rump LC, Simonaviciene A, Oberhauser V, Wessels S, Orth SR, et al. Effects of low dose sympathetic inhibition on glomerulosclerosis and albuminuria in subtotally nephrectomized rats. J Am Soc Nephrol. 2000;11(8):1469–78.
200. Bakris GL, Hart P, Ritz E. Beta blockers in the management of chronic kidney disease. Kidney Int. 2006;70(11):1905–13. doi:10.1038/sj.ki.5001835.
201. Cice G, Ferrara L, D'Andrea A, D'Isa S, Di Benedetto A, Cittadini A, et al. Carvedilol increases two-year survivalin dialysis patients with dilated cardiomyopathy: a prospective, placebo-controlled trial. J Am Coll Cardiol. 2003;41(9):1438–44.
202. Hausberg M, Tokmak F, Pavenstadt H, Kramer BK, Rump LC. Effects of moxonidine on sympathetic nerve activity in patients with end-stage renal disease. J Hypertens. 2010;28(9):1920–7. doi:10.1097/HJH.0b013e32833c2100.
203. Wallin BG, Sundlof G, Stromgren E, Aberg H. Sympathetic outflow to muscles during treatment of hypertension with metoprolol. Hypertension. 1984;6(4):557–62.
204. Burns J, Mary DA, Mackintosh AF, Ball SG, Greenwood JP. Arterial pressure lowering effect of chronic atenolol therapy in hypertension and vasoconstrictor sympathetic drive. Hypertension. 2004;44(4):454–8. doi:10.1161/01.HYP.0000141411.94596.0f.
205. Smithwick RH, Thompson JE. Splanchnicectomy for essential hypertension; results in 1,266 cases. J Am Med Assoc. 1953;152(16):1501–4.
206. Ravera M, Re M, Deferrari L, Vettoretti S, Deferrari G. Importance of blood pressure control in chronic kidney disease. J Am Soc Nephrol. 2006;17(4 Suppl 2):S98–103. doi:10.1681/asn.2005121319.
207. Kiuchi MG, Maia GL, de Queiroz Carreira MA, Kiuchi T, Chen S, Andrea BR, et al. Effects of renal denervation with a standard irrigated cardiac ablation catheter on blood pressure and renal function in patients with chronic kidney disease and resistant hypertension. Eur Heart J. 2013;34(28):2114–21. doi:10.1093/eurheartj/eht200.
208. Hering D, Lambert EA, Marusic P, Walton AS, Krum H, Lambert GW, et al. Substantial reduction in single sympathetic nerve firing after renal denervation in patients with resistant hypertension. Hypertension. 2013;61(2):457–64. doi:10.1161/hypertensionaha.111.00194.
209. Brinkmann J, Heusser K, Schmidt BM, Menne J, Klein G, Bauersachs J, et al. Catheter-based renal nerve ablation and centrally generated sympathetic activity in difficult-to-control hypertensive patients: prospective case series. Hypertension. 2012;60(6):1485–90. doi:10.1161/hypertensionaha.112.201186.
210. Hart EC, McBryde FD, Burchell AE, Ratcliffe LE, Stewart LQ, Baumbach A, et al. Translational examination of changes in baroreflex function after renal denervation in hypertensive rats and humans. Hypertension. 2013;62(3):533–41. doi:10.1161/hypertensionaha.113.01261.
211. Bhatt DL, Kandzari DE, O'Neill WW, D'Agostino R, Flack JM, Katzen BT, et al. A controlled trial of renal denervation for resistant hypertension. N Engl J Med. 2014;370(15):1393–401. doi:10.1056/NEJMoa1402670.
212. Jin Y, Persu A, Staessen JA. Renal denervation in the management of resistant hypertension: current evidence and perspectives. Curr Opin Nephrol Hypertens. 2013;22(5):511–8. doi:10.1097/MNH.0b013e3283640024.
213. Grassi G, Bertoli S, Seravalle G. Sympathetic nervous system: role in hypertension and in chronic kidney disease. Curr Opin Nephrol Hypertens. 2012;21(1):46–51. doi:10.1097/MNH.0b013e32834db45d.
214. Heusser K, Tank J, Engeli S, Diedrich A, Menne J, Eckert S, et al. Carotid baroreceptor stimulation, sympathetic activity, baroreflex function, and blood pressure in hypertensive patients. Hypertension. 2010;55(3):619–26. doi:10.1161/hypertensionaha.109.140665.
215. Lohmeier TE, Iliescu R, Dwyer TM, Irwin ED, Cates AW, Rossing MA. Sustained suppression of sympathetic activity and arterial pressure during chronic activation of the carotid baroreflex. Am J Physiol Heart Circ Physiol. 2010;299(2):H402–9. doi:10.1152/ajpheart.00372.2010.
216. Goddard J, Turner AN. Kidney and urinary tract disease. In: Walker BR, Colledge NR, Ralston SH, Penman ID, editors. Davidson's principles and practice of medicine. 22nd ed. Philadelphia: Churchill Livingstone Elsevier; 2014.
217. Chesterton LJ, Selby NM, Burton JO, Fialova J, Chan C, McIntyre CW. Categorization of the hemodynamic response to hemodialysis: the importance of baroreflex sensitivity. Hemodial Int Int Symp Home Hemodial. 2010;14(1):18–28. doi:10.1111/j.1542-4758.2009.00403.x.
218. Giordano M, Manzella D, Paolisso G, Caliendo A, Varricchio M, Giordano C. Differences in heart rate variability parameters during the post-dialytic period in type II diabetic and non-diabetic ESRD patients. Nephrol Dial Transplant. 2001;16(3):566–73.
219. Mylonopoulou M, Tentolouris N, Antonopoulos S, Mikros S, Katsaros K, Melidonis A, et al. Heart rate variability in advanced chronic kidney disease with or without diabetes: midterm effects of the initiation of chronic haemodialysis therapy. Nephrol Dial Transplant. 2010;25(11):3749–54. doi:10.1093/ndt/gfq226.
220. Chan CT, Chertow GM, Daugirdas JT, Greene TH, Kotanko P, Larive B, et al. Effects of daily hemodialysis on heart rate variability: results from the Frequent Hemodialysis Network (FHN) daily trial. Nephrol Dial Transplant. 2014;29(1):168–78. doi:10.1093/ndt/gft212.
221. Zilch O, Vos PF, Oey PL, Cramer MJ, Ligtenberg G, Koomans HA, et al. Sympathetic hyperactivity in haemodialysis patients is reduced by short daily haemodialysis. J Hypertens. 2007;25(6):1285–9. doi:10.1097/HJH.0b013e3280f9df85.
222. Korejwo G, Hermann A, Zdrojewski Z, Debska-Slizien A, Rutkowski B. Improved autonomic function after kidney transplantation. Transplant Proc. 2002;34(2):601–3.
223. Yang YW, Wu CH, Tsai MK, Kuo TB, Yang CC, Lee PH. Heart rate variability during hemodialysis and following renal transplantation. Transplant Proc. 2010;42(5):1637–40. doi:10.1016/j.transproceed.2010.01.062.
224. Heidbreder E, Schafferhans K, Heidland A. Disturbances of peripheral and autonomic nervous system in chronic renal failure: effects of hemodialysis and transplantation. Clin Nephrol. 1985;23(5):222–8.