Uraemia: an unrecognized driver of central neurohumoral dysfunction in chronic kidney disease?

Acta Physiologica

Volumn 219, Issue 1, 2017, Pages 305-323

  Underwood, C F ^a   Hildreth, C M ^a   Wyse, B F ^a   Boyd, R ^a   Goodchild, A K ^a   Phillips, J K ^a  

^a MACQUARIE UNIVERSITY   (Australia)

Author keywords

baroreflex; chronic kidney disease; hypertension; sympathetic; uraemia; vasopressin

Indexed keywords

ANGIOTENSIN II; NEUROHORMONE; NITRIC OXIDE; SUPEROXIDE; UREMIC TOXIN; VASOPRESSIN;

CENTRAL NERVOUS SYSTEM; CHRONIC KIDNEY FAILURE; ENDOCRINE DISEASE; HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; INFLAMMATION; LPK RAT; NERVE CELL; NEUROHUMORAL DYSFUNCTION; NONHUMAN; PRESSORECEPTOR REFLEX; PRIORITY JOURNAL; REVIEW; SENSORY NERVE; SYMPATHETIC NERVE; UREMIA; VASOPRESSIN RELEASE; ADRENERGIC SYSTEM; ANIMAL; BRAIN; HUMAN; HYPERTENSION; PATHOPHYSIOLOGY; PHYSIOLOGY;

ANIMALS; BAROREFLEX; BRAIN; HUMANS; HYPERTENSION; RENAL INSUFFICIENCY, CHRONIC; SYMPATHETIC NERVOUS SYSTEM; UREMIA;

EID: 84977472967     PISSN: 17481708     EISSN: 17481716     Source Type: Journal    
DOI: 10.1111/apha.12727     Document Type: Review

References (221)

1. Abbott, N.J. 2002. Astrocyte-endothelial interactions and blood-brain barrier permeability. J Anat 200, 629–638.
2. Abbott, N.J., Patabendige, A.A., Dolman, D.E., Yusof, S.R. & Begley, D.J. 2010. Structure and function of the blood-brain barrier. Neurobiol Dis 37, 13–25.
3. Abernethy, W.B., Bell, M.A., Morris, M. & Moody, D.M. 1993. Microvascular density of the human paraventricular nucleus decreases with aging but not hypertension. Exp Neurol 121, 270–274.
4. Adijiang, A., Goto, S., Uramoto, S., Nishijima, F. & Niwa, T. 2008. Indoxyl sulphate promotes aortic calcification with expression of osteoblast-specific proteins in hypertensive rats. Nephrol Dial Transplant 23, 1892–1901.
5. Agarwal, A., Anand, I.S., Sakhuja, V. & Chugh, K.S. 1991. Effect of dialysis and renal transplantation on autonomic dysfunction in chronic renal failure. Kidney Int 40, 489–495.
6. Amann, K., Rump, L.C., Simonaviciene, A., Oberhauser, V., Wessels, S., Orth, S.R., Gross, M.L., Koch, A., Bielenberg, G.W., Van Kats, J.P., Ehmke, H., Mall, G. & Ritz, E. 2000. Effects of low dose sympathetic inhibition on glomerulosclerosis and albuminuria in subtotally nephrectomized rats. J Am Soc Nephrol 11, 1469–1478.
7. Amann, K., Koch, A., Hofstetter, J., Gross, M.L., Haas, C., Orth, S.R., Ehmke, H., Rump, L.C. & Ritz, E. 2001. Glomerulosclerosis and progression: effect of subantihypertensive doses of alpha and beta blockers. Kidney Int 60, 1309–1323.
8. Ameer, O.Z., Hildreth, C.M. & Phillips, J.K. 2014. Sympathetic overactivity prevails over the vascular amplifier phenomena in a chronic kidney disease rat model of hypertension. Physiol Rep 2, e12205.
9. Ang, S.A., Harrison, J.L., Powers-Martin, K., Reddrop, C., McKitrick, D.J., Holobotovskyy, W., Arnolda, L.F. & Phillips, J.K. 2007. C-fos activation in renal hypertension. Proceedings of the High Blood Pressure Research Council of Australia 2006 Annual Scientific Meeting. Australia, Hypertension.
10. Argent, N.B., Burrell, L.M., Goodship, T.H., Wilkinson, R. & Baylis, P.H. 1991. Osmoregulation of thirst and vasopressin release in severe chronic renal failure. Kidney Int 39, 295–300.
11. Aronov, P.A., Luo, F.J., Plummer, N.S., Quan, Z., Holmes, S., Hostetter, T.H. & Meyer, T.W. 2011. Colonic contribution to uremic solutes. J Am Soc Nephrol 22, 1769–1776.
12. Augustyniak, R.A., Picken, M.M., Leonard, D., Zhou, X.J., Zhang, W. & Victor, R.G. 2010. Sympathetic nerves and the progression of chronic kidney disease during 5/6 nephrectomy: studies in sympathectomized rats. Clin Exp Pharmacol Physiol 37, 12–18.
13. Bailey, T.W., Jin, Y.H., Doyle, M.W., Smith, S.M. & Andresen, M.C. 2006. Vasopressin inhibits glutamate release via two distinct modes in the brainstem. J Neurosci 26, 6131–6142.
14. Bankir, L., Bouby, N. & Trinh-Trang-Tan, M.M. 1989. Possible involvement of vasopressin and urine concentrating process in the progression of chronic renal failure. Kidney Int Suppl 27, S32–S37.
15. Banks, W.A. 2005. Blood-brain barrier transport of cytokines: a mechanism for neuropathology. Curr Pharm Des 11, 973–984.
16. Barreto, F.C., Barreto, D.V., Liabeuf, S., Meert, N., Glorieux, G., Temmar, M., Choukroun, G., Vanholder, R. & Massy, Z.A. 2009. Serum indoxyl sulfate is associated with vascular disease and mortality in chronic kidney disease patients. Clin J Am Soc Nephrol 4, 1551–1558.
17. Bavanandan, S., Ajayi, S., Fentum, B., Paul, S.K., Carr, S.J. & Robinson, T.G. 2005. Cardiac baroreceptor sensitivity: a prognostic marker in predialysis chronic kidney disease patients. Kidney Int 67, 1019–1027.
18. Baylis, C. 2006. Arginine, arginine analogs and nitric oxide production in chronic kidney disease. Nat Clin Pract Nephrol 2, 209–220.
19. Biancardi, V.C. & Stern, J.E. 2016. Compromised blood-brain barrier permeability: novel mechanism by which circulating angiotensin II signals sympathoexcitatory centers during hypertension. J Physiol 594, 1591–1600.
20. Biancardi, V.C., Son, S.J., Ahmadi, S., Filosa, J.A. & Stern, J.E. 2014. Circulating angiotensin II gains access to the hypothalamus and brain stem during hypertension via breakdown of the blood-brain barrier. Hypertension 63, 572–579.
21. Blum, M., Yachnin, T., Wollman, Y., Chernihovsky, T., Peer, G., Grosskopf, I., Kaplan, E., Silverberg, D., Cabili, S. & Iaina, A. 1998. Low nitric oxide production in patients with chronic renal failure. Nephron 79, 265–268.
22. Bolton, C.H., Downs, L.G., Victory, J.G., Dwight, J.F., Tomson, C.R., Mackness, M.I. & Pinkney, J.H. 2001. Endothelial dysfunction in chronic renal failure: roles of lipoprotein oxidation and pro-inflammatory cytokines. Nephrol Dial Transplant 16, 1189–1197.
23. Bouby, N., Bachmann, S., Bichet, D. & Bankir, L. 1990. Effect of water intake on the progression of chronic renal failure in the 5/6 nephrectomized rat. Am J Physiol 258, F973–F979.
24. Brown, C.H., Bull, P.M. & Bourque, C.W. 2004. Phasic bursts in rat magnocellular neurosecretory cells are not intrinsically regenerative in vivo. Eur J Neurosci 19, 2977–2983.
25. Brown, C.H., Bains, J.S., Ludwig, M. & Stern, J.E. 2013. Physiological regulation of magnocellular neurosecretory cell activity: integration of intrinsic, local and afferent mechanisms. J Neuroendocrinol 25, 678–710.
26. Cachofeiro, V., Goicochea, M., de Vinuesa, S.G., Oubina, P., Lahera, V. & Luno, J. 2008. Oxidative stress and inflammation, a link between chronic kidney disease and cardiovascular disease. Kidney Int Suppl 74, S4–S9.
27. Calabrese, V., Mancuso, C., Calvani, M., Rizzarelli, E., Butterfield, D.A. & Stella, A.M. 2007. Nitric oxide in the central nervous system: neuroprotection versus neurotoxicity. Nat Rev Neurosci 8, 766–775.
28. Cardounel, A.J. & Zweier, J.L. 2002. Endogenous methylarginines regulate neuronal nitric-oxide synthase and prevent excitotoxic injury. J Biol Chem 277, 33995–34002.
29. Chan, C.T., Harvey, P.J., Picton, P., Pierratos, A., Miller, J.A. & Floras, J.S. 2003. Short-term blood pressure, noradrenergic, and vascular effects of nocturnal home hemodialysis. Hypertension 42, 925–931.
30. Chan, C.T., Jain, V., Picton, P., Pierratos, A. & Floras, J.S. 2005a. Nocturnal hemodialysis increases arterial baroreflex sensitivity and compliance and normalizes blood pressure of hypertensive patients with end-stage renal disease. Kidney Int 68, 338–344.
31. Chan, S.H., Hsu, K.S., Huang, C.C., Wang, L.L., Ou, C.C. & Chan, J.Y. 2005b. NADPH oxidase-derived superoxide anion mediates angiotensin II-induced pressor effect via activation of p38 mitogen-activated protein kinase in the rostral ventrolateral medulla. Circ Res 97, 772–780.
32. Chan, S.H., Tai, M.H., Li, C.Y. & Chan, J.Y. 2006. Reduction in molecular synthesis or enzyme activity of superoxide dismutases and catalase contributes to oxidative stress and neurogenic hypertension in spontaneously hypertensive rats. Free Radic Biol Med 40, 2028–2039.
33. Chan, C.T., Shen, X.S., Picton, P. & Floras, J. 2008. Nocturnal home hemodialysis improves baroreflex effectiveness index of end-stage renal disease patients. J Hypertens 26, 1795–1800.
34. Chou, A.H., Lee, C.M., Chen, C.Y., Liou, J.T., Liu, F.C., Chen, Y.L. & Day, Y.J. 2014. Hippocampal transcriptional dysregulation after renal ischemia and reperfusion. Brain Res 1582, 197–210.
35. Converse, R.L. Jr, Jacobsen, T.N., Toto, R.D., Jost, C.M., Cosentino, F., Fouad-Tarazi, F. & Victor, R.G. 1992. Sympathetic overactivity in patients with chronic renal failure. N Engl J Med 327, 1912–1918.
36. Couser, W.G., Remuzzi, G., Mendis, S. & Tonelli, M. 2011. The contribution of chronic kidney disease to the global burden of major noncommunicable diseases. Kidney Int 80, 1258–1270.
37. Crum, R., Fairchild, R., Bronsther, O., Dominic, W., Ward, D., Fernandez, R. & Brown, M.R. 1991. Neuroendocrinology of chronic renal failure and renal transplantation. Transplantation 52, 818–823.
38. Danielsen, H., Nielsen, A.H., Pedersen, E.B., Herlevsen, P., Kornerup, H.J. & Posborg, V. 1986. Exaggerated natriuresis in adult polycystic kidney disease. Acta Med Scand 219, 59–66.
39. De Deyn, P.P., Marescau, B., Cuykens, J.J., Van Gorp, L., Lowenthal, A. & De Potter, W.P. 1987. Guanidino compounds in serum and cerebrospinal fluid of non-dialyzed patients with renal insufficiency. Clin Chim Acta 167, 81–88.
40. De Deyn, P.P., Marescau, B., D'Hooge, R., Possemiers, I., Nagler, J. & Mahler, C. 1995. Guanidino compound levels in brain regions of non-dialyzed uremic patients. Neurochem Int 27, 227–237.
41. De Deyn, P.P., Vanholder, R. & D'Hooge, R. 2003. Nitric oxide in uremia: effects of several potentially toxic guanidino compounds. Kidney Int Suppl 84, S25–S28.
42. De Deyn, P.P., Vanholder, R., Eloot, S. & Glorieux, G. 2009. Guanidino compounds as uremic (neuro)toxins. Semin Dial 22, 340–345.
43. Degaspari, S., Tzanno-Martins, C.B., Fujihara, C.K., Zatz, R., Branco-Martins Jã, P., Viel, T.A., Buck, H.S., Orellana, A.M.M., Böhmer, A.E., de Sá Lima, L., Andreotti, D.Z., Munhoz, C.D., Scavone, C. & Kawamoto, E.M. 2015. Altered KLOTHO and NF-κB-TNF-α signaling are correlated with nephrectomy-induced cognitive impairment in rats. PLoS ONE 10, e0125271.
44. Di, S. & Tasker, J.G. 2004. Dehydration-induced synaptic plasticity in magnocellular neurons of the hypothalamic supraoptic nucleus. Endocrinology 145, 5141–5149.
45. Ellis, R.J., Small, D.M., Vesey, D.A., Johnson, D.W., Francis, R., Vitetta, L., Gobe, G.C. & Morais, C. 2016. Indoxyl sulphate and kidney disease: causes, consequences and interventions. Nephrology 21, 170–177.
46. Eloot, S., Schepers, E., Barreto, D.V., Barreto, F.C., Liabeuf, S., Van Biesen, W., Verbeke, F., Glorieux, G., Choukroun, G., Massy, Z. & Vanholder, R. 2011. Estimated glomerular filtration rate is a poor predictor of concentration for a broad range of uremic toxins. Clin J Am Soc Nephrol 6, 1266–1273.
47. Fagugli, R.M., De Smet, R., Buoncristiani, U., Lameire, N. & Vanholder, R. 2002. Behavior of non-protein-bound and protein-bound uremic solutes during daily hemodialysis. Am J Kidney Dis 40, 339–347.
48. Farina, C., Aloisi, F. & Meinl, E. 2007. Astrocytes are active players in cerebral innate immunity. Trends Immunol 28, 138–145.
49. Finley, K.H. 1939. The capillary beds of the paraventricular and supra-optic nuclei of the hypothalamus. J Comp Neurol 71, 1–19.
50. Fisher, J.P., Young, C.N. & Fadel, P.J. 2009. Central sympathetic overactivity: maladies and mechanisms. Auton Neurosci 148, 5–15.
51. Fleck, C., Schweitzer, F., Karge, E., Busch, M. & Stein, G. 2003. Serum concentrations of asymmetric (ADMA) and symmetric (SDMA) dimethylarginine in patients with chronic kidney diseases. Clin Chim Acta 336, 1–12.
52. Franklin, S.S. & Wong, N.D. 2013. Hypertension and cardiovascular disease: contributions of the Framingham heart study. Global Heart 8, 49–57.
53. Glorieux, G.L., Dhondt, A.W., Jacobs, P., Van Langeraert, J., Lameire, N.H., De Deyn, P.P. & Vanholder, R.C. 2004. In vitro study of the potential role of guanidines in leukocyte functions related to atherogenesis and infection. Kidney Int 65, 2184–2192.
54. Go, A.S., Chertow, G.M., Fan, D., McCulloch, C.E. & Hsu, C.-Y. 2004. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 351, 1296–1305.
55. Gobel, U., Schrock, H., Seller, H. & Kuschinsky, W. 1990. Glucose utilization, blood flow and capillary density in the ventrolateral medulla of the rat. Pflugers Arch 416, 477–480.
56. Goicoechea, M., Garcia de Vinuesa, S., Verdalles, U., Verde, E., Macias, N., Santos, A., Perez de Jose, A., Cedeno, S., Linares, T. & Luno, J. 2015. Allopurinol and progression of CKD and cardiovascular events: long-term follow-up of a randomized clinical trial. Am J Kidney Dis 65, 543–549.
57. Grassi, G., Quarti-Trevano, F., Seravalle, G., Arenare, F., Volpe, M., Furiani, S., Dell'Oro, R. & Mancia, G. 2011a. Early sympathetic activation in the initial clinical stages of chronic renal failure. Hypertension 57, 846–851.
58. Grassi, G., Seravalle, G., Ghiadoni, L., Tripepi, G., Bruno, R.M., Mancia, G. & Zoccali, C. 2011b. Sympathetic nerve traffic and asymmetric dimethylarginine in chronic kidney disease. Clin J Am Soc Nephrol 6, 2620–2627.
59. Griva, K., Thompson, D., Jayasena, D., Davenport, A., Harrison, M. & Newman, S.P. 2006. Cognitive functioning pre- to post-kidney transplantation–a prospective study. Nephrol Dial Transplant 21, 3275–3282.
60. Guyenet, P.G. 2006. The sympathetic control of blood pressure. Nat Rev Neurosci 7, 335–346.
61. Hailpern, S.M., Melamed, M.L., Cohen, H.W. & Hostetter, T.H. 2007. Moderate chronic kidney disease and cognitive function in adults 20 to 59 years of age: third national health and nutrition examination survey (NHANES III). J Am Soc Nephrol 18, 2205–2213.
62. Hanisch, U.K. 2002. Microglia as a source and target of cytokines. Glia 40, 140–155.
63. Harada, S., Tokunaga, S., Momohara, M., Masaki, H., Tagawa, T., Imaizumi, T. & Takeshita, A. 1993. Inhibition of nitric oxide formation in the nucleus tractus solitarius increases renal sympathetic nerve activity in rabbits. Circ Res 72, 511–516.
64. Hausberg, M., Kosch, M., Harmelink, P., Barenbrock, M., Hohage, H., Kisters, K., Dietl, K.H. & Rahn, K.H. 2002. Sympathetic nerve activity in end-stage renal disease. Circulation 106, 1974–1979.
65. Hildreth, C.M., Kandukuri, D.S., Goodchild, A.K. & Phillips, J.K. 2013. Temporal development of baroreceptor dysfunction in a rodent model of chronic kidney disease. Clin Exp Pharmacol Physiol 40, 458–465.
66. Ho, T.A., Godefroid, N., Gruzon, D., Haymann, J.P., Marechal, C., Wang, X., Serra, A., Pirson, Y. & Devuyst, O. 2012. Autosomal dominant polycystic kidney disease is associated with central and nephrogenic defects in osmoregulation. Kidney Int 82, 1121–1129.
67. Hosoya, K. & Tachikawa, M. 2011. Roles of organic anion/cation transporters at the blood-brain and blood-cerebrospinal fluid barriers involving uremic toxins. Clin Exp Nephrol 15, 478–485.
68. Iitake, K., Kimura, T., Matsui, K., Ota, K., Shoji, M., Inoue, M. & Yoshinaga, K. 1985. Effect of haemodialysis on plasma ADH levels, plasma renin activity and plasma aldosterone levels in patients with end-stage renal disease. Acta Endocrinol 110, 207–213.
69. Ishii, M., Ikeda, T., Takagi, M., Sugimoto, T., Atarashi, K., Igari, T., Uehara, Y., Matsuoka, H., Hirata, Y., Kimura, K., Takeda, T. & Murao, S. 1983. Elevated plasma catecholamines in hypertensives with primary glomerular diseases. Hypertension 5, 545–551.
70. Iwata, K., Watanabe, H., Morisaki, T., Matsuzaki, T., Ohmura, T., Hamada, A. & Saito, H. 2007. Involvement of indoxyl sulfate in renal and central nervous system toxicities during cisplatin-induced acute renal failure. Pharm Res 24, 662–671.
71. Jangula, A. & Murphy, E.J. 2013. Lipopolysaccharide-induced blood brain barrier permeability is enhanced by alpha-synuclein expression. Neurosci Lett 551, 23–27.
72. Japundzic-Zigon, N. 2013. Vasopressin and oxytocin in control of the cardiovascular system. Curr Neuropharmacol 11, 218–230.
73. Jeewandara, T.M., Ameer, O.Z., Boyd, R., Wyse, B.F., Underwood, C.F. & Phillips, J.K. 2015. Protective cardiorenal effects of spironolactone in a rodent model of polycystic kidney disease. Clin Exp Pharmacol Physiol 42, 353–360.
74. Jensen, J.M., Mose, F.H., Kulik, A.E., Bech, J.N., Fenton, R.A. & Pedersen, E.B. 2014. Abnormal urinary excretion of NKCC2 and AQP2 in response to hypertonic saline in chronic kidney disease: an intervention study in patients with chronic kidney disease and healthy controls. BMC Nephrol 15, 101.
75. Jin, J.S. & D'Alecy, L.G. 1996. Central and peripheral effects of asymmetric dimethylarginine, an endogenous nitric oxide synthetase inhibitor. J Cardiovasc Pharmacol 28, 439–446.
76. Johansson, M., Gao, S.A., Friberg, P., Annerstedt, M., Carlstrom, J., Ivarsson, T., Jensen, G., Ljungman, S., Mathillas, O., Nielsen, F.D. & Strombom, U. 2007. Baroreflex effectiveness index and baroreflex sensitivity predict all-cause mortality and sudden death in hypertensive patients with chronic renal failure. J Hypertens 25, 163–168.
77. John, S.G., Sigrist, M.K. & McIntyre, C.W. 2008. Impaired baroreflex sensitivity predicts mortality in chronic kidney disease. Computers in Cardiology, 2008. Computers in Cardiology, Bologna.
78. Kadekaro, M., Terrell, M.L., Liu, H., Gestl, S., Bui, V. & Summy-Long, J.Y. 1998. Effects of L-NAME on cerebral metabolic, vasopressin, oxytocin, and blood pressure responses in hemorrhaged rats. Am J Physiol 274, R1070–R1077.
79. Kang, Y.M., Ma, Y., Zheng, J.P., Elks, C., Sriramula, S., Yang, Z.M. & Francis, J. 2009. Brain nuclear factor-kappa B activation contributes to neurohumoral excitation in angiotensin II-induced hypertension. Cardiovasc Res 82, 503–512.
80. Kasimay, O., Sener, G., Cakir, B., Yuksel, M., Cetinel, S., Contuk, G. & Yegen, B.C. 2009. Estrogen protects against oxidative multiorgan damage in rats with chronic renal failure. Ren Fail 31, 711–725.
81. Keith, D.S., Nichols, G.A., Gullion, C.M., Brown, J. & Smith, D.H. 2004. Longitudinal follow-up and outcomes among a population with chronic kidney disease in a large managed care organization. Arch Intern Med 164, 659–663.
82. Kielstein, J.T., Boger, R.H., Bode-Boger, S.M., Frolich, J.C., Haller, H., Ritz, E. & Fliser, D. 2002. Marked increase of asymmetric dimethylarginine in patients with incipient primary chronic renal disease. J Am Soc Nephrol 13, 170–176.
83. Kimura, N., Masuda, S., Katsura, T. & Inui, K. 2009. Transport of guanidine compounds by human organic cation transporters, hOCT1 and hOCT2. Biochem Pharmacol 77, 1429–1436.
84. King, R.S. & Glickman, J.D. 2010. Electrolyte management in frequent home hemodialysis. Semin Dial 23, 571–574.
85. Kishi, T., Hirooka, Y., Mukai, Y., Shimokawa, H. & Takeshita, A. 2003. Atorvastatin causes depressor and sympatho-inhibitory effects with upregulation of nitric oxide synthases in stroke-prone spontaneously hypertensive rats. J Hypertens 21, 379–386.
86. Klahr, S., Levey, A.S., Beck, G.J., Caggiula, A.W., Hunsicker, L., Kusek, J.W. & Striker, G. 1994. The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease. N Engl J Med 330, 877–884.
87. Klein, I.H., Ligtenberg, G., Oey, P.L., Koomans, H.A. & Blankestijn, P.J. 2001. Sympathetic activity is increased in polycystic kidney disease and is associated with hypertension. J Am Soc Nephrol 12, 2427–2433.
88. Klein, I.H., Ligtenberg, G., Neumann, J., Oey, P.L., Koomans, H.A. & Blankestijn, P.J. 2003a. Sympathetic nerve activity is inappropriately increased in chronic renal disease. J Am Soc Nephrol 14, 3239–3244.
89. Klein, I.H., Ligtenberg, G., Oey, P.L., Koomans, H.A. & Blankestijn, P.J. 2003b. Enalapril and losartan reduce sympathetic hyperactivity in patients with chronic renal failure. J Am Soc Nephrol 14, 425–430.
90. Kokot, F., Grzeszczak, W., Zukowska-Szczechowska, E. & Wiecek, A. 1989. Water immersion-induced alterations of plasma atrial natriuretic peptide level and its relationship to the renin-angiotensin-aldosterone system and vasopressin secretion in acute and chronic renal failure. Clin Nephrol 31, 247–252.
91. Kramer, L., Madl, C., Stockenhuber, F., Yeganehfar, W., Eisenhuber, E., Derfler, K., Lenz, K., Schneider, B. & Grimm, G. 1996. Beneficial effect of renal transplantation on cognitive brain function. Kidney Int 49, 833–838.
92. Kubo, T. & Kihara, M. 1990. Modulation of the aortic baroreceptor reflex by neuropeptide Y, neurotensin and vasopressin microinjected into the nucleus tractus solitarii of the rat. Naunyn Schmiedebergs Arch Pharmacol 342, 182–188.
93. Kuncova, J., Sviglerova, J., Kummer, W., Rajdl, D., Chottova-Dvorakova, M., Tonar, Z., Nalos, L. & Stengl, M. 2009. Parasympathetic regulation of heart rate in rats after 5/6 nephrectomy is impaired despite functionally intact cardiac vagal innervation. Nephrol Dial Transplant 24, 2362–2370.
94. Kurella, M., Chertow, G.M., Luan, J. & Yaffe, K. 2004. Cognitive impairment in chronic kidney disease. J Am Geriatr Soc 52, 1863–1869.
95. Kurihara, I., Saito, T., Obara, K., Shoji, Y., Hirai, M., Soma, J., Sato, H., Imai, Y. & Abe, K. 1996. Effect of a nonpeptide vasopressin V1 antagonist (OPC-21268) on experimental accelerated focal glomerulosclerosis. Nephron 73, 629–636.
96. La Rovere, M.T., Specchia, G., Mortara, A. & Schwartz, P.J. 1988. Baroreflex sensitivity, clinical correlates, and cardiovascular mortality among patients with a first myocardial infarction. A prospective study. Circulation 78, 816–824.
97. Lacy, P., Carr, S.J., O'Brien, D., Fentum, B., Williams, B., Paul, S.K. & Robinson, T.G. 2006. 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 110, 101–108.
98. Lazarus, J.M., Hampers, C. & Merrill, J.P. 1974. Hypertension in chronic renal failure. Treatment with hemodialysis and nephrectomy. Arch Intern Med 133, 1059–1066.
99. Levitan, D., Massry, S.G., Romoff, M. & Campese, V.M. 1984. Plasma catecholamines and autonomic nervous system function in patients with early renal insufficiency and hypertension: effect of clonidine. Nephron 36, 24–29.
100. Li, Z. & Ferguson, A.V. 1993. Angiotensin ii responsiveness of rat paraventricular and subfornical organ neurons in vitro. Neuroscience 55, 197–207.
101. Liang, Z., Shi, X.M., Liu, L.F., Chen, X.P., Shan, Z.L., Lin, K., Li, J., Chen, F.K., Li, Y.G., Guo, H.Y. & Wang, Y.T. 2015. Renal denervation suppresses atrial fibrillation in a model of renal impairment. PLoS ONE 10, e0124123.
102. Ligtenberg, G., Blankestijn, P.J., Oey, P.L., Klein, I.H.H., Dijkhorst-Oei, L.-T., Boomsma, F., Wieneke, G.H., van Huffelen, A.C. & Koomans, H.A. 1999. Reduction of sympathetic hyperactivity by enalapril in patients with chronic renal failure. N Engl J Med 340, 1321–1328.
103. Liu, Q.S., Jia, Y.S. & Ju, G. 1997. Nitric oxide inhibits neuronal activity in the supraoptic nucleus of the rat hypothalamic slices. Brain Res Bull 43, 121–125.
104. Liu, M., Liang, Y., Chigurupati, S., Lathia, J.D., Pletnikov, M., Sun, Z., Crow, M., Ross, C.A., Mattson, M.P. & Rabb, H. 2008. Acute kidney injury leads to inflammation and functional changes in the brain. J Am Soc Nephrol 19, 1360–1370.
105. Lopez-Ramirez, M.A., Fischer, R., Torres-Badillo, C.C., Davies, H.A., Logan, K., Pfizenmaier, K., Male, D.K., Sharrack, B. & Romero, I.A. 2012. Role of caspases in cytokine-induced barrier breakdown in human brain endothelial cells. J Immunol 189, 3130–3139.
106. Lu, P., Gonzales, C., Chen, Y., Adedoyin, A., Hummel, M., Kennedy, J.D. & Whiteside, G.T. 2009. CNS penetration of small molecules following local inflammation, widespread systemic inflammation or direct injury to the nervous system. Life Sci 85, 450–456.
107. Mahmoodi, B.K., Matsushita, K., Woodward, M., Blankestijn, P.J., Cirillo, M., Ohkubo, T., Rossing, P., Sarnak, M.J., Stengel, B., Yamagishi, K., Yamashita, K., Zhang, L., Coresh, J., de Jong, P.E. & Astor, B.C. 2012. Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without hypertension: a meta-analysis. Lancet 380, 1649–1661.
108. Mallamaci, F., Tripepi, G., Maas, R., Malatino, L., Boger, R. & Zoccali, C. 2004. Analysis of the relationship between norepinephrine and asymmetric dimethyl arginine levels among patients with end-stage renal disease. J Am Soc Nephrol 15, 435–441.
109. Massion, P.B., Feron, O., Dessy, C. & Balligand, J.L. 2003. Nitric oxide and cardiac function: ten years after, and continuing. Circ Res 93, 388–398.
110. Mastorakos, G., Weber, J.S., Magiakou, M.A., Gunn, H. & Chrousos, G.P. 1994. Hypothalamic-pituitary-adrenal axis activation and stimulation of systemic vasopressin secretion by recombinant interleukin-6 in humans: potential implications for the syndrome of inappropriate vasopressin secretion. J Clin Endocrinol Metab 79, 934–939.
111. Matsumura, K., Abe, I., Tsuchihashi, T. & Fujishima, M. 1998. Central nitric oxide attenuates the baroreceptor reflex in conscious rabbits. Am J Physiol 274, R1142–R1149.
112. Matsushita, K., van der Velde, M., Astor, B.C., Woodward, M., Levey, A.S., de Jong, P.E., Coresh, J. & Gansevoort, R.T. 2010. Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality: a collaborative meta-analysis of general population cohorts. Lancet 375, 2073–2081.
113. Mayhan, W.G. 2002. Cellular mechanisms by which tumor necrosis factor-alpha produces disruption of the blood-brain barrier. Brain Res 927, 144–152.
114. Meijer, E., Boertien, W.E., Zietse, R. & Gansevoort, R.T. 2011. Potential deleterious effects of vasopressin in chronic kidney disease and particularly autosomal dominant polycystic kidney disease. Kidney Blood Press Res 34, 235–244.
115. Meijers, B.K. & Evenepoel, P. 2011. The gut-kidney axis: indoxyl sulfate, p-cresyl sulfate and CKD progression. Nephrol Dial Transplant 26, 759–761.
116. Meijers, B.K., Bammens, B., De Moor, B., Verbeke, K., Vanrenterghem, Y. & Evenepoel, P. 2008. Free p-cresol is associated with cardiovascular disease in hemodialysis patients. Kidney Int 73, 1174–1180.
117. Menon, V., Gul, A. & Sarnak, M.J. 2005. Cardiovascular risk factors in chronic kidney disease. Kidney Int 68, 1413–1418.
118. Michalski, A. & Grzeszczak, W. 1996. The effect of hypervolemia on electrolyte level and and level of volume regulating hormones in patients with autosomal dominant polycystic kidney disease. Pol Arch Med Wewn 96, 329–343.
119. Michelini, L.C. & Stern, J.E. 2009. Exercise-induced neuronal plasticity in central autonomic networks: role in cardiovascular control. Exp Physiol 94, 947–960.
120. Moradi, H., Sica, D.A. & Kalantar-Zadeh, K. 2013. Cardiovascular burden associated with uremic toxins in patients with chronic kidney disease. Am J Nephrol 38, 136–148.
121. Morgenthaler, N.G., Struck, J., Alonso, C. & Bergmann, A. 2006. Assay for the measurement of copeptin, a stable peptide derived from the precursor of vasopressin. Clin Chem 52, 112–119.
122. Mortara, A., La Rovere, M.T., Pinna, G.D., Prpa, A., Maestri, R., Febo, O., Pozzoli, M., Opasich, C. & Tavazzi, L. 1997. Arterial baroreflex modulation of heart rate in chronic heart failure: clinical and hemodynamic correlates and prognostic implications. Circulation 96, 3450–3458.
123. Muting, D. 1965. Studies on the pathogenesis of uremia. Comparative determinations of glucuronic acid, indican, free and bound phenols in the serum, cerebrospinal fluid, and urine of renal diseases with and without uremia. Clin Chim Acta 12, 551–554.
124. Naud, J., Laurin, L.P., Michaud, J., Beauchemin, S., Leblond, F.A. & Pichette, V. 2012. Effects of chronic renal failure on brain drug transporters in rats. Drug Metab Dispos 40, 39–46.
125. Navaneethan, S.D. & Beddhu, S. 2009. Associations of serum uric acid with cardiovascular events and mortality in moderate chronic kidney disease. Nephrol Dial Transplant 24, 1260–1266.
126. Neirynck, N., Eloot, S., Glorieux, G., Barreto, D.V., Barreto, F.C., Liabeuf, S., Lenglet, A., Lemke, H.D., Massy, Z.A. & Vanholder, R. 2012. Estimated glomerular filtration rate is a poor predictor of the concentration of middle molecular weight uremic solutes in chronic kidney disease. PLoS ONE 7, e44201.
127. Neirynck, N., Vanholder, R., Schepers, E., Eloot, S., Pletinck, A. & Glorieux, G. 2013. An update on uremic toxins. Int Urol Nephrol 45, 139–150.
128. Neumann, J., Ligtenberg, G., Oey, L., Koomans, H.A. & Blankestijn, P.J. 2004. Moxonidine normalizes sympathetic hyperactivity in patients with eprosartan-treated chronic renal failure. J Am Soc Nephrol 15, 2902–2907.
129. Nicco, C., Wittner, M., DiStefano, A., Jounier, S., Bankir, L. & Bouby, N. 2001. Chronic exposure to vasopressin upregulates ENaC and sodium transport in the rat renal collecting duct and lung. Hypertension 38, 1143–1149.
130. Nigam, S.K., Wu, W., Bush, K.T., Hoenig, M.P., Blantz, R.C. & Bhatnagar, V. 2015. Handling of drugs, metabolites, and uremic toxins by kidney proximal tubule drug transporters. Clin J Am Soc Nephrol 10, 2039–2049.
131. Noguera, I., Medina, P., Segarra, G., Martínez, M.C., Aldasoro, M., Vila, J.M. & Lluch, S. 1997. Potentiation by vasopressin of adrenergic vasoconstriction in the rat isolated mesenteric artery. Br J Pharmacol 122, 431–438.
132. Nongnuch, A., Panorchan, K. & Davenport, A. 2014. Brain-kidney crosstalk. Crit Care 18, 225.
133. Nunes, F.C., Ribeiro, T.P., Franca-Silva, M.S., Medeiros, I.A. & Braga, V.A. 2010. Superoxide scavenging in the rostral ventrolateral medulla blunts the pressor response to peripheral chemoreflex activation. Brain Res 1351, 141–149.
134. Ogawa, K., Hirooka, Y., Shinohara, K., Kishi, T. & Sunagawa, K. 2012. Inhibition of oxidative stress in rostral ventrolateral medulla improves impaired baroreflex sensitivity in stroke-prone spontaneously hypertensive rats. Int Heart J 53, 193–198.
135. Okada, H., Suzuki, H., Kanno, Y., Yamamura, Y. & Saruta, T. 1994. Effects of vasopressin V1 and V2 receptor antagonists on progressive renal failure in rats. Clin Sci (Lond) 86, 399–404.
136. Oliveira-Sales, E.B., Colombari, D.S., Davisson, R.L., Kasparov, S., Hirata, A.E., Campos, R.R. & Paton, J.F. 2010. Kidney-induced hypertension depends on superoxide signaling in the rostral ventrolateral medulla. Hypertension 56, 290–296.
137. Oshima, N., Onimaru, H., Matsubara, H., Uchida, T., Watanabe, A., Takechi, H., Nishida, Y. & Kumagai, H. 2015. Uric acid, indoxyl sulfate, and methylguanidine activate bulbospinal neurons in the RVLM via their specific transporters and by producing oxidative stress. Neuroscience 304, 133–145.
138. Ow, C.P., Abdelkader, A., Hilliard, L.M., Phillips, J.K. & Evans, R.G. 2014. Determinants of renal tissue hypoxia in a rat model of polycystic kidney disease. Am J Physiol Regul Integr Comp Physiol 307, R1207–R1215.
139. Palkovits, M., Sebekova, K., Gallatz, K., Boor, P., Sebekova, K. Jr, Klassen, A., Bahner, U. & Heidland, A. 2009. Neuronal activation in the CNS during different forms of acute renal failure in rats. Neuroscience 159, 862–882.
140. Penne, E.L., van der Weerd, N.C., Blankestijn, P.J., van den Dorpel, M.A., Grooteman, M.P.C., Nubé, M.J., ter Wee, P.M., Lévesque, R. & Bots, M.L. 2010. Role of residual kidney function and convective volume on change in β(2)-microglobulin levels in hemodiafiltration patients. Clin J Am Soc Nephrol 5, 80–86.
141. Pereira, B.J., Shapiro, L., King, A.J., Falagas, M.E., Strom, J.A. & Dinarello, C.A. 1994. Plasma levels of IL-1 beta, TNF alpha and their specific inhibitors in undialyzed chronic renal failure, CAPD and hemodialysis patients. Kidney Int 45, 890–896.
142. Perico, N., Zoja, C., Corna, D., Rottoli, D., Gaspari, F., Haskell, L. & Remuzzi, G. 2009. V1/V2 vasopressin receptor antagonism potentiates the renoprotection of renin-angiotensin system inhibition in rats with renal mass reduction. Kidney Int 76, 960–967.
143. Phillips, J.K., Hopwood, D., Loxley, R.A., Ghatora, K., Coombes, J.D., Tan, Y.S., Harrison, J.L., McKitrick, D.J., Holobotvskyy, V., Arnolda, L.F. & Rangan, G.K. 2007. 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 30, 129–144.
144. Ponte, B., Pruijm, M., Ackermann, D., Vuistiner, P., Guessous, I., Ehret, G., Alwan, H., Youhanna, S., Paccaud, F., Mohaupt, M. et al. 2015. Copeptin is associated with kidney length, renal function, and prevalence of simple cysts in a population-based study. J Am Soc Nephrol 26, 1415–1425.
145. Potapenko, E.S., Biancardi, V.C., Florschutz, R.M., Ryu, P.D. & Stern, J.E. 2011. Inhibitory-excitatory synaptic balance is shifted toward increased excitation in magnocellular neurosecretory cells of heart failure rats. J Neurophysiol 106, 1545–1557.
146. Raj, D.S., Ouwendyk, M., Francoeur, R. & Pierratos, A. 2000. Beta(2)-microglobulin kinetics in nocturnal haemodialysis. Nephrol Dial Transplant 15, 58–64.
147. Ramchandra, R., Hood, S.G. & May, C.N. 2014. Central exogenous nitric oxide decreases cardiac sympathetic drive and improves baroreflex control of heart rate in ovine heart failure. Am J Physiol Regul Integr Comp Physiol 307, R271–R280.
148. Rana, I., Kompa, A.R., Skommer, J., Wang, B.H., Lekawanvijit, S., Kelly, D.J., Krum, H. & Charchar, F.J. 2015. Contribution of microrna to pathological fibrosis in cardio-renal syndrome: impact of uremic toxins. Physiol Rep 3, e12371.
149. Reddy, Y.S., Kiranmayi, V.S., Bitla, A.R., Krishna, G.S., Rao, P.V. & Sivakumar, V. 2015. Nitric oxide status in patients with chronic kidney disease. Indian J Nephrol 25, 287–291.
150. Ridao, N., Luno, J., Garcia de Vinuesa, S., Gomez, F., Tejedor, A. & Valderrabano, F. 2001. Prevalence of hypertension in renal disease. Nephrol Dial Transplant 16(Suppl 1), 70–73.
151. Rossi, M., Campbell, K.L., Johnson, D.W., Stanton, T., Vesey, D.A., Coombes, J.S., Weston, K.S., Hawley, C.M., McWhinney, B.C., Ungerer, J.P. & Isbel, N. 2014. Protein-bound uremic toxins, inflammation and oxidative stress: a cross-sectional study in stage 3–4 chronic kidney disease. Arch Med Res 45, 309–317.
152. Sakuma, I., Togashi, H., Yoshioka, M., Saito, H., Yanagida, M., Tamura, M., Kobayashi, T., Yasuda, H., Gross, S.S. & Levi, R. 1992. 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 70, 607–611.
153. Salman, I.M., Hildreth, C.M., Ameer, O.Z. & Phillips, J.K. 2014. Differential contribution of afferent and central pathways to the development of baroreflex dysfunction in chronic kidney disease. Hypertension 63, 804–810.
154. Salman, I.M., Phillips, J.K., Ameer, O.Z. & Hildreth, C.M. 2015a. Abnormal central control underlies impaired baroreflex control of heart rate and sympathetic nerve activity in female Lewis polycystic kidney rats. J Hypertens 33, 1418–1428.
155. Salman, I.M., Sarma Kandukuri, D., Harrison, J.L., Hildreth, C.M. & Phillips, J.K. 2015b. Direct conscious telemetry recordings demonstrate increased renal sympathetic nerve activity in rats with chronic kidney disease. Front Physiol 6, 218.
156. Sánchez-Lozada, L.G., Soto, V., Tapia, E., Avila-Casado, C., Sautin, Y.Y., Nakagawa, T., Franco, M., Rodríguez-Iturbe, B. & Johnson, R.J. 2008. Role of oxidative stress in the renal abnormalities induced by experimental hyperuricemia. Am J Physiol Renal Physiol 295, F1134–F1141.
157. Sander, M., Chavoshan, B. & Victor, R.G. 1999. A large blood pressure-raising effect of nitric oxide synthase inhibition in humans. Hypertension 33, 937–942.
158. Sato, E., Tanaka, A., Oyama, J.I., Yamasaki, A., Shimomura, M., Hiwatashi, A., Ueda, Y., Amaha, M., Nomura, M., Matsumura, D., Nakamura, T. & Node, K. 2015. Long-term effects of AST-120 on the progression and prognosis of pre-dialysis chronic kidney disease: a 5-year retrospective study. Heart Vessels, doi:10.1007/s00380-015-0785-7.
159. Schlaich, M.P., Bart, B., Hering, D., Walton, A., Marusic, P., Mahfoud, F., Bohm, M., Lambert, E.A., Krum, H., Sobotka, P.A. et al. 2013. 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 168, 2214–2220.
160. Schmidt, R.J. & Baylis, C. 2000. Total nitric oxide production is low in patients with chronic renal disease. Kidney Int 58, 1261–1266.
161. Schneider, C.A., Rasband, W.S. & Eliceiri, K.W. 2012. NIH image to ImageJ: 25 years of image analysis. Nat Methods 9, 671–675.
162. Schohn, D., Weidmann, P., Jahn, H. & Beretta-Piccoli, C. 1985. Norepinephrine-related mechanism in hypertension accompanying renal failure. Kidney Int 28, 814–822.
163. Schrimpf, C., Gillmann, H.J., Sahlmann, B., Meinders, A., Larmann, J., Wilhelmi, M., Aper, T., Rustum, S., Lichtinghagen, R., Theilmeier, G. & Teebken, O.E. 2015. Renal function interferes with copeptin in prediction of major adverse cardiac events in patients undergoing vascular surgery. PLoS ONE 10, e0123093.
164. Segarra, G., Medina, P., Vila, J.M., Chuan, P., Domenech, C. & Lluch, S. 2002. Increased contraction to noradrenaline by vasopressin in human renal arteries. J Hypertens 20, 1373–1379.
165. Shi, B., Ni, Z., Zhou, W., Yu, Z., Gu, L., Mou, S., Fang, W., Wang, Q., Cao, L., Yan, Y. & Qian, J. 2010. Circulating levels of asymmetric dimethylarginine are an independent risk factor for left ventricular hypertrophy and predict cardiovascular events in pre-dialysis patients with chronic kidney disease. Eur J Intern Med 21, 444–448.
166. Shi, Z., Gan, X.B., Fan, Z.D., Zhang, F., Zhou, Y.B., Gao, X.Y., De, W. & Zhu, G.Q. 2011. Inflammatory cytokines in paraventricular nucleus modulate sympathetic activity and cardiac sympathetic afferent reflex in rats. Acta Physiol 203, 289–297.
167. Shimizu, H., Bolati, D., Adijiang, A., Muteliefu, G., Enomoto, A., Nishijima, F., Dateki, M. & Niwa, T. 2011. NF-kappaB plays an important role in indoxyl sulfate-induced cellular senescence, fibrotic gene expression, and inhibition of proliferation in proximal tubular cells. Am J Physiol Cell Physiol 301, C1201–C1212.
168. Shimizu, H., Hirose, Y., Goto, S., Nishijima, F., Zrelli, H., Zghonda, N., Niwa, T. & Miyazaki, H. 2012. Indoxyl sulfate enhances angiotensin II signaling through upregulation of epidermal growth factor receptor expression in vascular smooth muscle cells. Life Sci 91, 172–177.
169. Siddiqi, L., Prakken, N.H., Velthuis, B.K., Cramer, M.J., Oey, P.L., Boer, P., Bots, M.L. & Blankestijn, P.J. 2010. Sympathetic activity in chronic kidney disease patients is related to left ventricular mass despite antihypertensive treatment. Nephrol Dial Transplant 25, 3272–3277.
170. Siddiqi, L., Joles, J.A., Oey, P.L. & Blankestijn, P.J. 2011. Atorvastatin reduces sympathetic activity in patients with chronic kidney disease. J Hypertens 29, 2176–2180.
171. Sirich, T.L., Aronov, P.A., Plummer, N.S., Hostetter, T.H. & Meyer, T.W. 2013. Numerous protein-bound solutes are cleared by the kidney with high efficiency. Kidney Int 84, 585–590.
172. Son, S.J., Filosa, J.A., Potapenko, E.S., Biancardi, V.C., Zheng, H., Patel, K.P., Tobin, V.A., Ludwig, M. & Stern, J.E. 2013. Dendritic peptide release mediates interpopulation crosstalk between neurosecretory and preautonomic networks. Neuron 78, 1036–1049.
173. Sorrentino, R. & Pinto, A. 1995. Effect of methylguanidine on rat blood pressure: role of endothelial nitric oxide synthase. Br J Pharmacol 115, 510–514.
174. Sriramula, S., Cardinale, J.P. & Francis, J. 2013. Inhibition of TNF in the brain reverses alterations in ras components and attenuates angiotensin II-induced hypertension. PLoS ONE 8, e63847.
175. Srisawat, R., Ludwig, M., Bull, P.M., Douglas, A.J., Russell, J.A. & Leng, G. 2000. Nitric oxide and the oxytocin system in pregnancy. J Neurosci 20, 6721–6727.
176. Stern, J.E. 2004. Nitric oxide and homeostatic control: an intercellular signalling molecule contributing to autonomic and neuroendocrine integration? Prog Biophys Mol Biol 84, 197–215.
177. Strobel, J., Muller, F., Zolk, O., Endress, B., Konig, J., Fromm, M.F. & Maas, R. 2013. Transport of asymmetric dimethylarginine (ADMA) by cationic amino acid transporter 2 (CAT2), organic cation transporter 2 (OCT2) and multidrug and toxin extrusion protein 1 (MATE1). Amino Acids 45, 989–1002.
178. Suchy-Dicey, A.M., Laha, T., Hoofnagle, A., Newitt, R., Sirich, T.L., Meyer, T.W., Thummel, K.E., Yanez, N.D., Himmelfarb, J., Weiss, N.S. & Kestenbaum, B.R. 2015. Tubular secretion in CKD. J Am Soc Nephrol pii: ASN.2014121193. doi:10.1681/ASN.2014121193.
179. Sun, C.Y., Chang, S.C. & Wu, M.S. 2012. Uremic toxins induce kidney fibrosis by activating intrarenal renin-angiotensin-aldosterone system associated epithelial-to-mesenchymal transition. PLoS ONE 7, e34026.
180. Sun, H.J., Zhang, L.L., Fan, Z.D., Chen, D., Zhang, L., Gao, X.Y., Kang, Y.M. & Zhu, G.Q. 2014a. Superoxide anions involved in sympathoexcitation and pressor effects of salusin-beta in paraventricular nucleus in hypertensive rats. Acta Physiol 210, 534–545.
181. Sun, H.J., Zhou, H., Feng, X.M., Gao, Q., Ding, L., Tang, C.S., Zhu, G.Q. & Zhou, Y.B. 2014b. Superoxide anions in the paraventricular nucleus mediate cardiac sympathetic afferent reflex in insulin resistance rats. Acta Physiol 212, 267–282.
182. Takagishi, M., Waki, H., Bhuiyan, M.E., Gouraud, S.S., Kohsaka, A., Cui, H., Yamazaki, T., Paton, J.F. & Maeda, M. 2010. IL-6 microinjected in the nucleus tractus solitarii attenuates cardiac baroreceptor reflex function in rats. Am J Physiol Regul Integr Comp Physiol 298, R183–R190.
183. Thomas, G., Xie, D., Chen, H.Y., Anderson, A.H., Appel, L.J., Bodana, S., Brecklin, C.S., Drawz, P., Flack, J.M., Miller, E.R. III, Steigerwalt, S.P., Townsend, R.R., Weir, M.R., Wright, J.T. Jr & Rahman, M. 2016. Prevalence and prognostic significance of apparent treatment resistant hypertension in chronic kidney disease: report from the chronic renal insufficiency cohort study. Hypertension 67, 387–396.
184. Tinucci, T., Abrahao, S.B., Santello, J.L. & Mion, D. Jr 2001. Mild chronic renal insufficiency induces sympathetic overactivity. J Hum Hypertens 15, 401–406.
185. Tonelli, M., Wiebe, N., Culleton, B., House, A., Rabbat, C., Fok, M., McAlister, F. & Garg, A.X. 2006. Chronic kidney disease and mortality risk: a systematic review. J Am Soc Nephrol 17, 2034–2047.
186. Torres, V.E. 2015. Vasopressin receptor antagonists, heart failure, and polycystic kidney disease. Annu Rev Med 66, 195–210.
187. Tozawa, M., Iseki, K., Iseki, C., Kinjo, K., Ikemiya, Y. & Takishita, S. 2003. Blood pressure predicts the risk of developing end-stage renal disease in men and women. Hypertension 41, 1341–1345.
188. Tramonti, G., Cipollini, I., Annichiarico, C., Lorusso, P., Panicucci, E., Mariani, G. & Barsotti, G. 2012. Creatinine clearance, cystatin C, beta2-microglobulin and TATI as markers of renal function in patients with proteinuria. J Nephrol 25, 976–982.
189. Tumur, Z. & Niwa, T. 2009. Indoxyl sulfate inhibits nitric oxide production and cell viability by inducing oxidative stress in vascular endothelial cells. Am J Nephrol 29, 551–557.
190. Tyagi, N., Sedoris, K.C., Steed, M., Ovechkin, A.V., Moshal, K.S. & Tyagi, S.C. 2005. Mechanisms of homocysteine-induced oxidative stress. Am J Physiol Heart Circ Physiol 289, H2649–H2656.
191. Ueno, S., Sano, A., Kotani, K., Kondoh, K. & Kakimoto, Y. 1992. Distribution of free methylarginines in rat tissues and in the bovine brain. J Neurochem 59, 2012–2016.
192. Vanholder, R., Baurmeister, U., Brunet, P., Cohen, G., Glorieux, G. & Jankowski, J. 2008. A bench to bedside view of uremic toxins. J Am Soc Nephrol 19, 863–870.
193. Vanholder, R., Eloot, S., Schepers, E., Neirynck, N., Glorieux, G. & Massy, Z. 2012. An obituary for GFR as the main marker for kidney function? Semin Dial 25, 9–14.
194. VanNess, J.M., Hinojosa-Laborde, C., Craig, T. & Haywood, J.R. 1999. Effect of sinoaortic deafferentation on renal wrap hypertension. Hypertension 33, 476–481.
195. Viaene, L., Annaert, P., de Loor, H., Poesen, R., Evenepoel, P. & Meijers, B. 2013. Albumin is the main plasma binding protein for indoxyl sulfate and p-cresyl sulfate. Biopharm Drug Dispos 34, 165–175.
196. Viaene, L., Meijers, B.K., Bammens, B., Vanrenterghem, Y. & Evenepoel, P. 2014. Serum concentrations of p-cresyl sulfate and indoxyl sulfate, but not inflammatory markers, increase in incident peritoneal dialysis patients in parallel with loss of residual renal function. Perit Dial Int 34, 71–78.
197. Watanabe, H., Miyamoto, Y., Honda, D., Tanaka, H., Wu, Q., Endo, M., Noguchi, T., Kadowaki, D., Ishima, Y., Kotani, S. et al. 2013. P-cresyl sulfate causes renal tubular cell damage by inducing oxidative stress by activation of NADPH oxidase. Kidney Int 83, 582–592.
198. Weiss, N., Miller, F., Cazaubon, S. & Couraud, P.O. 2009. The blood-brain barrier in brain homeostasis and neurological diseases. Biochim Biophys Acta 1788, 842–857.
199. Wever, R., Boer, P., Hijmering, M., Stroes, E., Verhaar, M., Kastelein, J., Versluis, K., Lagerwerf, F., van Rijn, H., Koomans, H. & Rabelink, T. 1999. Nitric oxide production is reduced in patients with chronic renal failure. Arterioscler Thromb Vasc Biol 19, 1168–1172.
200. Winchester, J.F. & Audia, P.F. 2006. Extracorporeal strategies for the removal of middle molecules. Semin Dial 19, 110–114.
201. Wu, I.W., Hsu, K.H., Hsu, H.J., Lee, C.C., Sun, C.Y., Tsai, C.J. & Wu, M.S. 2012. Serum free p-cresyl sulfate levels predict cardiovascular and all-cause mortality in elderly hemodialysis patients–a prospective cohort study. Nephrol Dial Transplant 27, 1169–1175.
202. Xia, Y. & Krukoff, T.L. 2003. Differential neuronal activation in the hypothalamic paraventricular nucleus and autonomic/neuroendocrine responses to ICV endotoxin. Neuroscience 121, 219–231.
203. Xiao, S., Schmidt, R.J. & Baylis, C. 2000. Plasma from ESRD patients inhibits nitric oxide synthase activity in cultured human and bovine endothelial cells. Acta Physiol Scand 168, 175–179.
204. Xiao, S., Wagner, L., Schmidt, R.J. & Baylis, C. 2001. Circulating endothelial nitric oxide synthase inhibitory factor in some patients with chronic renal disease. Kidney Int 59, 1466–1472.
205. Yang, C.R., Phillips, M.I. & Renaud, L.P. 1992. Angiotensin II receptor activation depolarizes rat supraoptic neurons in vitro. Am J Physiol 263, R1333–R1338.
206. Yao, S.T. & May, C.N. 2013. Intra-carotid angiotensin II activates tyrosine hydroxylase-expressing rostral ventrolateral medulla neurons following blood-brain barrier disruption in rats. Neuroscience 245, 148–156.
207. Yao, Y., Hildreth, C.M., Farnham, M.M., Saha, M., Sun, Q.J., Pilowsky, P.M. & Phillips, J.K. 2015. The effect of losartan on differential reflex control of sympathetic nerve activity in chronic kidney disease. J Hypertens 33, 1249–1260.
208. Ye, S., Zhong, H., Yanamadala, S. & Campese, V.M. 2006. Oxidative stress mediates the stimulation of sympathetic nerve activity in the phenol renal injury model of hypertension. Hypertension 48, 309–315.
209. Yeh, Y.C., Huang, M.F., Liang, S.S., Hwang, S.J., Tsai, J.C., Liu, T.L., Wu, P.H., Yang, Y.H., Kuo, K.C., Kuo, M.C. & Chen, C.S. 2016. Indoxyl sulfate, not p-cresyl sulfate, is associated with cognitive impairment in early-stage chronic kidney disease. Neurotoxicology 53, 148–152.
210. Yisireyili, M., Shimizu, H., Saito, S., Enomoto, A., Nishijima, F. & Niwa, T. 2013. Indoxyl sulfate promotes cardiac fibrosis with enhanced oxidative stress in hypertensive rats. Life Sci 92, 1180–1185.
211. Young, C.N., Fisher, J.P., Gallagher, K.M., Whaley-Connell, A., Chaudhary, K., Victor, R.G., Thomas, G.D. & Fadel, P.J. 2009. Inhibition of nitric oxide synthase evokes central sympatho-excitation in healthy humans. J Physiol 587, 4977–4986.
212. Zanzinger, J., Czachurski, J. & Seller, H. 1995. Inhibition of basal and reflex-mediated sympathetic activity in the RVLM by nitric oxide. Am J Physiol 268, R958–R962.
213. van der Zee, S., Thompson, A., Zimmerman, R., Lin, J., Huan, Y., Braskett, M., Sciacca, R.R., Landry, D.W. & Oliver, J.A. 2007. Vasopressin administration facilitates fluid removal during hemodialysis. Kidney Int 71, 318–324.
214. Zgoda-Pols, J.R., Chowdhury, S., Wirth, M., Milburn, M.V., Alexander, D.C. & Alton, K.B. 2011. Metabolomics analysis reveals elevation of 3-indoxyl sulfate in plasma and brain during chemically-induced acute kidney injury in mice: investigation of nicotinic acid receptor agonists. Toxicol Appl Pharmacol 255, 48–56.
215. Zhang, K., Mayhan, W.G. & Patel, K.P. 1997. Nitric oxide within the paraventricular nucleus mediates changes in renal sympathetic nerve activity. Am J Physiol 273, R864–R872.
216. Zhang, Y., Yu, Y., Zhang, F., Zhong, M.K., Shi, Z., Gao, X.Y., Wang, W. & Zhu, G.Q. 2006. NAD(P)H oxidase in paraventricular nucleus contributes to the effect of angiotensin II on cardiac sympathetic afferent reflex. Brain Res 1082, 132–141.
217. Zhong, M.K., Gao, J., Zhang, F., Xu, B., Fan, Z.D., Wang, W. & Zhu, G.Q. 2009. Reactive oxygen species in rostral ventrolateral medulla modulate cardiac sympathetic afferent reflex in rats. Acta Physiol 197, 297–304.
218. Zilch, O., Vos, P.F., Oey, P.L., Cramer, M.J., Ligtenberg, G., Koomans, H.A. & Blankestijn, P.J. 2007. Sympathetic hyperactivity in haemodialysis patients is reduced by short daily haemodialysis. J Hypertens 25, 1285–1289.
219. Zimmerman, M.C. 2011. Angiotensin II and angiotensin-1-7 redox signaling in the central nervous system. Curr Opin Pharmacol 11, 138–143.
220. Zittema, D., van den Berg, E., Meijer, E., Boertien, W.E., Muller Kobold, A.C., Franssen, C.F., de Jong, P.E., Bakker, S.J., Navis, G. & Gansevoort, R.T. 2014. Kidney function and plasma copeptin levels in healthy kidney donors and autosomal dominant polycystic kidney disease patients. Clin J Am Soc Nephrol 9, 1553–1562.
221. Zoccali, C., Mallamaci, F., Parlongo, S., Cutrupi, S., Benedetto, F.A., Tripepi, G., Bonanno, G., Rapisarda, F., Fatuzzo, P., Seminara, G., Cataliotti, A., Stancanelli, B., Malatino, L.S. & Cateliotti, A. 2002. Plasma norepinephrine predicts survival and incident cardiovascular events in patients with end-stage renal disease. Circulation 105, 1354–1359.