Objectives and Methods: Two thirds of men with end-stage kidney disease (ESKD) have serum testosterone levels in the hypogonadal range. We examined if low serum testoster- one levels were correlated with measures of endothelial dysfunction in ESKD. Bilateral common carotid artery (CCA) intima-media thickness (IMT) and atherosclerotic plaque occurrence, left ventricular mass index, flow- (FMD) and nitrate-mediated vasodilatation (NMD) of the brachial artery were determined by ultrasound imaging in 100 nondiabetic men with ESKD (50 men exhibited androgen deficiency; serum testosterone concentrations <300 ng/dl). Results: Left-ventricular mass index, CCA diameter, CCA-IMT and atherosclerotic plaque occurrence were all significantly increased in ESKD patients with androgen deficiency compared with patients without androgen deficiency (p < 0.05). Also, FMD and NMD measurements were significantly reduced in the former compared with the latter (p < 0.05). Testosterone levels were inversely correlated with age and duration of hemodialysis therapy (r = –0.44 and r = –0.55; p < 0.001). Testosterone levels were negatively correlated to CCA-IMT and atherosclerotic plaque occurrence in patients with androgen deficiency (r = –0.32, p < 0.003, and r = –0.23, p < 0.04, respectively). FMD and NMD measurements were positively correlated to total (r = 0.65 and r = 0.61; both p < 0.0001) and free (r = 0.52 and r = 0.48; both p < 0.001) testosterone levels in patients with low androgenicity. Conclusion: The present results indicated that ESKD patients with androgen deficiency had increased CCA-IMT, atherosclerotic plaque occurrence and reduced FMD and NMD compared with patients without androgen deficiency. Testosterone serum levels were negatively correlated to CCA-IMT and positively correlated to endothelium-dependent vasodilatation in ESKD patients with androgen deficiency.

1.
Handelsman DJ, Dong Q: Hypothalamo-pituitary gonadal axis in chronic renal failure. Endocrinol Metab North Am 1993;22:145–159.
2.
Holdsworth J, Atkins RC, Deketser DM: The pituitary-testicular axis in men with chronic renal failure. N Engl J Med 1977;296:1245–1249.
3.
Sawin CT, Langcope C, Schmidt GW, Ryan RG: Blood levels of gonadotropins and gonadal hormones in gynecomastia associated with chronic hemodialysis. J Clin Endocrinol Metab 1973;36:988–994.
4.
Wheatley T, Clark PMS, Clark JDA, Raggatt PR, Evans D, Holder R: Pulsatility of luteinizing hormone in men with chronic renal failure: abnormal rather than absent. Br Med J 1987;294:482–483.
5.
Levitan D, Moser S, Goldstein DA, Kletzky O, Lobo R, Massry SG: Disturbances in the hypothalamic-pituitary-gonadal axis in male patients with acute renal failure. Am J Nephrol 1984;4:99–106.
6.
Woodrow G, Oldroyd B, Turney J, Tomkins L, Brownjohn A, Smith M: Whole body and regional body composition in patients with chronic renal failure. Nephrol Dial Transplant 1996;11:1613–1618.
7.
Lawrence IG, Price DE, Howlett TA, Harris KPG, Feehally J, Walls J: Correcting impotence in the male dialysis patients: experience with testosterone replacement and vacuum tumescence therapy. Am J Kidney Dis 1998;31:313–319.
8.
Pollock CA, Allen B, Warden RA, Caterson RJ, Blagojevic N, Cocksedge B, Mahony JF, Waugh DA, Ibels LS: Total body nitrogen by neutron activation in maintenance hemodialysis. Am J Kidney Dis 1990;16:38–45.
9.
Hakim R, Levin N: Malnutrition in hemodialysis patients. Am J Kidney Dis 1993;21:125–137.
10.
Lazarus J: Nutrition in hemodialysis patients. Am J Kidney Dis 1993;21:99–105.
11.
Gutman R, Stead W, Robinson R: Physical activity and employment status of patients on maintenance dialysis. N Engl J Med 1981;304:309–313.
12.
Dockery F, Bulpitt CJ, Donaldson M, Fernandez S, Rajkumar C: The relationship between androgens and arterial stiffness in older men. J Am Geriatr Soc 2003;51:1627–1632.
13.
Ahimastos AA, Formosa M, Dart AM, Kingwell BA: Gender differences in large artery stiffness pre- and post puberty. J Clin Endocrinol Metab 2003;88:5375–5380.
14.
Wenger NK, Speroff L, Packard B: Cardiovascular health and disease in women. N Engl J Med 1993;329:247–256.
15.
Lindner A, Charra B, Sherrard DJ, Scribner BH: Accelerated atherosclerosis in prolonged maintenance hemodialysis. N Engl J Med 1974;290:697–701.
16.
Luke RG: Chronic renal failure – a vasculopathic state. N Engl J Med 1998;339:841–843.
17.
Kari JA, Donald AE, Vallace DT, Bruckdorfer KR, Leone A, Mullen MJ, Bunce T, Dorado B, Deanfield JE, Rees L: Physiology and biochemistry of endothelial function in children with chronic renal failure. Kidney Int 1997;52:468–472.
18.
Van Guldener C, Lambert J, Jansen MJ, Steyn M, Donker AJ, Stehouwer CD: Endothelium dependent vasodilation is impaired in peritoneal dialysis patients. Nephrol Dial Transplant 1998;13:1782–1786.
19.
Van Guldener C, Lambert J, Jansen MJ, Donker AJ, Stehouwer CD: Endothelium dependent vasodilation and distensibility of large arteries in chronic hemodialysis patients. Nephrol Dial Transplant 1997;12(suppl 2):14–18.
20.
Joannides R, Bakkali RH, LeRoy F, Rivault O, Godin M, Moore N, Fillastre JP, Thuillez C: Altered flow dependent vaso-dilation of conduit arteries in maintenance hemodialysis. Nephrol Dial Transplant 1997;12:2623–2628.
21.
Morris ST, McMurray JJ, Rodger RS, Jardine AG: Impaired endothelium-dependent vasodilation in uremia. Nephrol Dial Transplant 2000;16:1194–2000.
22.
Karakitsos D, De Groot E, Patrianakos AP, Parthenakis F, Boletis J, Karabinis A, Kyriazis J, Vardas P, Daphnis E: Adiponectin and cardiovascular remodeling in end-stage renal disease and co-morbid diabetes mellitus. Am J Nephrol 2006;5:340–347.
23.
Singh AB, Norris K, Modi N, Sinha-Hikim I, Shen R, Davidson T, Bhasin S: Pharmacokinetics of a transdermal testosterone system in men with end stage renal disease receiving maintenance hemodialysis and healthy hypogonadal men. J Clin Endocrinol Metab 2001;86:2437–2445.
24.
Charra B, Calemard E, Ruffet M, Chazot C, Terrat JC, Vanel T, Laurent G: Survival as an index of adequacy of dialysis. Kidney Int 1992;41:1286–1291.
25.
Patrianakos A, Karakitsos D, De Groot E, Parthenakis F, Daphnis E, Vardas P: Alteration of the proximal aorta biophysical properties in patients with end-stage renal disease. Heart 2006;9:228–232.
26.
Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H, Gutgesell H, Reichek N, Sahn D, Schnittger I, et al: Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two- Dimensional Echocardiograms. J Am Soc Echocardiogr 1989;2:358–367.
27.
Devereux RB, Reichek N: Echocardiographic determination of left ventricular mass in man: anatomic validation of the method. Circulation 1977;55:613–618.
28.
Hoeks APG, Brands PJ, Smeets FA, Reneman RS: Assessment of distensibility of superficial arteries. Ultrasound Med Biol 1990;16:121–128.
29.
De Groot E, Hovingh K, Wiegman A, Duriez P, Smit AJ, Fruchart JC, Kastelein JJ: Measurement of arterial wall thickness as a surrogate marker for atherosclerosis. Circulation 2004;109:33–38.
30.
Celermajer DS, Sorensen KE, Gooch VM, et al: Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 1992;340:1111–1115.
31.
Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, Deanfield J, Drexler H, Gerhard-Herman M, et al: Guidelines for ultrasound assessment of endothelium-dependent flow-mediated vasodilatation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol 2002;39:257–265.
32.
Zadeh JA, Koutsamainis KG, Roberts AP, Curtis JR, Daly JR: The effect of maintenance hemodialysis and renal transplantation on the plasma testosterone levels of male patients in chronic renal failure. Acta Endocrinol 1975;80:577–582.
33.
Bhasin S, Storer TW, Javanbakht M, Berman N, Yarasheski KE, Philips J, Dike M, Sinha-Hikim I, Shen R, Hays RD, Beall G: Testosterone replacement and resistance exercise in HIV-infected men with weight loss and low testosterone levels. JAMA 2000;284:763–770.
34.
Celermajer DS, Adams MR, Clarkson P, Robinson J, McCredie R, Donald A, Deanfield JE: Passive smoking and impaired endothelium-dependent arterial dilatation in healthy young adults. N Engl J Med 1996;334:150–154.
35.
Janssens SP, Shimouchi A, Quertermous T, Bloch DB, Bloch KD: Cloning and expression of a cDNA encoding human endothelium-derived relaxing factor/nitric oxide synthase. J Biol Chem 1992;267:22694.
36.
Cooke JP: Asymmetrical dimethylarginine: the Uber marker? Circulation 2004;109:1813.
37.
Steudel W, Ichinose F, Huang PL, Hurford WE, Jones RC, Bevan JE, Fishman MC, Zapol WM: Pulmonary vasoconstriction and hypertension in mice with targeted disruption of the endothelial nitric oxide synthase (NOS 3) gene. Circ Res 1997;81:34–41.
38.
Davignon J, Ganz P: Role of endothelial dysfunction in atherosclerosis. Circulation 2004;109:III27–III32.
39.
Lundman P, Eriksson MJ, Stuhlinger M, Cooke JP, Hamsten A, Tornvall P: Mild-to-moderate hypertriglyceridemia in young men is associated with endothelial dysfunction and increased plasma concentrations of asymmetric dimethylarginine. J Am Coll Cardiol 2001;38:111–116.
40.
Shoji T, Emoto M, Shinohara K, Kakiya R, Tsujimoto Y, Kishimoto H, Ishimura E, Tabata T, Nishizawa Y: Diabetes mellitus, aortic stiffness, and cardiovascular mortality in end-stage renal disease. J Am Soc Nephrol 2001;12:2117–2124.
41.
Miyazaki H, Matsuoka H, Itabe H, Usui M, Ueda S, Okuda S, Imaizumi T: Hemodialysis impairs endothelial function via oxidative stress. Effect of vitamin E-coated dialyzer. Circulation 2001;101:1002–1006.
42.
Kosch M, Levers A, Barenbrock M, Matzkies F, Schaefer RM, Kisters K, Rahn KH, Hausberg M: Acute effects of hemodialysis on endothelial function and large artery elasticity. Nephrol Dial Transplant 2001;16:1663–1668.
43.
Levine GN, Frei B, Koulouris SN, Gerhard MD, Keaney JF Jr, Vita JA: Ascorbic acid reverses endothelial vasomotor dysfunction in patients with coronary artery disease. Circulation 1996;93:1107–1113.
44.
Sydow K, Schwedhelm E, Arakawa N, Bode-Boger SM, Tsikas D, Hornig B, Frolich JC, Boger RH: ADMA and oxidative stress are responsible for endothelial dysfunction in hyper-homocyst(e)inemia: effects of L-arginine and B vitamins. Cardiovasc Res 2003;57:244–252.
45.
Wada Y, Matsuoka H, Tamai O, Kohno K, Okuda S, Imaizumi T: Erythropoietin impairs endothelium-dependent vasorelaxation through cyclooxygenase-dependent mechanisms in humans. Am J Hypertens 1999;12:980–987.
46.
Schmidt RJ, Baylis C: Total nitric oxide production is low in patients with chronic renal disease. Kidney Int 2000;58:1261–1266.
47.
Vallance P, Leone A, Calver A, Collier J, Moncada S: Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure. Lancet 1992;339:572–575.
48.
Foresta C, Caretta N, Lana A, De Toni L, Biagioli A, Ferlin A, Garolla A: Reduced number of circulating endothelial progenitor cells in hypogonadal men. J Clin Endocrinol Metab 2006;91:4599–4602.
49.
Ghiadoni L, Cupisti A, Huang Y, Mattei P, Cardinal H, Favilla S, Rindi P, Barsotti G, Taddei S, Salvetti A: Endothelial dysfunction and oxidative stress in chronic renal failure. J Nephrol 2004;17:512–519.
50.
Yilmaz MI, Saglam M, Caglar K, Cakir E, Sonmez A, Ozgurtas T, Aydin A, Eyileten T, Ozcan O, Acikel C, Tasar M, Genctoy G, Erbil K, Vural A, Zoccali C: The determinants of endothelial dysfunction in CKD: oxidative stress and asymmetric dimethylarginine. Am J Kidney Dis 2006;47:42–50.
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