Background: Cardiovascular mortality is high in hemodialysis (HD) patients. Early arterial pressure wave reflections, reflecting arterial stiffness and the endogenous nitric oxide synthesis inhibitor asymmetric dimethylarginine (ADMA) levels predict mortality in HD patients. Therefore, we aimed to study changes in ADMA levels and central arterial pressure waveform during HD. Methods: Thirty-two chronic HD patients were studied before and after a HD session. In a subset of 22 patients without arrhythmias, pulse wave analysis was performed on radial artery (SphygmoCor). Augmentation index (AIx), defined as difference between the second and first systolic peak divided by central pulse pressure, was used as a measure of arterial stiffness. ADMA was measured in plasma with the ELISA technique. Homocysteine was measured in plasma using the EIA technique. Results: HD reduced both AIx (19%; p = 0.003) and ADMA levels (17%; p < 0.001). The magnitudes of changes in AIx and ADMA during HD were correlated (r = 0.44; p = 0.045). Mean arterial pressure change was not significant. HD reduced homocysteine levels, but homocysteine was not related to ADMA or AIx. Conclusion: The reduction in ADMA level seen after HD was associated with improvement in the central arterial pressure waveform, suggesting involvement of nitric oxide in the regulation of arterial stiffness in HD patients.

1.
Sarnak MJ, Levey AS, Schoolwerth AC, et al: Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American heart association councils on kidney in cardiovascular disease, high blood pressure research, clinical cardiology, and epidemiology and prevention. Circulation 2003;108:2154&ndash;2169.
2.
Meier-Kriesche HU, Port FK, Ojo AO, et al: Effect of waiting time on renal transplant outcome. Kidney Int 2000;58:1311&ndash;1317.
3.
London G, Guerin A, Pannier B, et al: Increased systolic pressure in chronic uremia. Role of arterial wave reflections. Hypertension 1992;20:10&ndash;19.
4.
Joannides R, Bakkali EH, Le Roy F, et al: Altered flow-dependent vasodilatation of conduit arteries in maintenance haemodialysis. Nephrol Dial Transplant 1997;12:2623&ndash;2628.
5.
O&rsquo;Rourke MF, Staessen JA, Vlachopoulos C, Duprez D, Plante GE: Clinical applications of arterial stiffness; definitions and reference values. Am J Hypertens 2002;15:426&ndash;444.
6.
Wilkinson IB, Franklin SS, Cockcroft JR: Nitric oxide and the regulation of large artery stiffness: from physiology to pharmacology. Hypertension 2004;44:112&ndash;116.
7.
London GM, Blacher J, Pannier B, et al: Arterial wave reflections and survival in end-stage renal failure. Hypertension 2001;38:434&ndash;438.
8.
Zoccali C, Bode-Boger S, Mallamaci F, et al: Plasma concentration of asymmetrical dimethylarginine and mortality in patients with end-stage renal disease: a prospective study. Lancet 2001;358:2113&ndash;2117.
9.
Kielstein JT, Boger RH, Bode-Boger SM, et al: Asymmetric dimethylarginine plasma concentrations differ in patients with end-stage renal disease: Relationship to treatment method and atherosclerotic disease. J Am Soc Nephrol 1999;10:594&ndash;600.
10.
Covic A, Goldsmith DJ, Panaghiu L, Covic M, Sedor J: Analysis of the effect of hemodialysis on peripheral and central arterial pressure waveforms. Kidney Int 2000;57:2634&ndash;2643.
11.
Cross JM, Donald A, Vallance PJ, et al: Dialysis improves endothelial function in humans. Nephrol Dial Transplant 2001;16:1823&ndash;1829.
12.
Boger RH, Zoccali C: Adma: A novel risk factor that explains excess cardiovascular event rate in patients with end-stage renal disease. Atheroscler Suppl 2003;4:23&ndash;28.
13.
Mardare NG, Goldsmith DJ, Gusbeth-Tatomir P, Covic A: Intradialytic changes in reflective properties of the arterial system during a single hemodialysis session. Hemodial Int 2005;9:376&ndash;382.
14.
O&rsquo;Rourke MF, Gallagher DE: Pulse wave analysis. J Hypertens 1996;14(suppl):S147&ndash;S157.
15.
Savage MT, Ferro CJ, Pinder SJ, Tomson CR: Reproducibility of derived central arterial waveforms in patients with chronic renal failure. Clin Sci (Lond) 2002;103:59&ndash;65.
16.
Schulze F, Wesemann R, Schwedhelm E, et al: Determination of asymmetric dimethylarginine (ADMA) using a novel ELISA assay. Clin Chem Lab Med 2004;42:1377&ndash;1383.
17.
Bergstrom J, Wehle B: No change in corrected beta 2-microglobulin concentration after cuprophane haemodialysis. Lancet 1987;i: 628&ndash;629.
18.
Zoccali C, Mallamaci F, Maas R, et al: Left ventricular hypertrophy, cardiac remodeling and asymmetric dimethylarginine (ADMA) in hemodialysis patients. Kidney Int 2002;62:339&ndash;345.
19.
Kielstein JT, Impraim B, Simmel S, et al: Cardiovascular effects of systemic nitric oxide synthase inhibition with asymmetrical dimethylarginine in humans. Circulation 2004;109:172&ndash;177.
20.
Kielstein JT, Donnerstag F, Gasper S, et al: Adma increases arterial stiffness and decreases cerebral blood flow in humans. Stroke 2006;37:2024&ndash;2029.
21.
Hand MF, Haynes WG, Webb DJ: Hemodialysis and L-arginine, but not D-arginine, correct renal failure-associated endothelial dysfunction. Kidney Int 1998;53:1068&ndash;1077.
22.
Mittermayer F, Schaller G, Pleiner J, et al: Asymmetrical dimethylarginine plasma concentrations are related to basal nitric oxide release but not endothelium-dependent vasodilation of resistance arteries in peritoneal dialysis patients. J Am Soc Nephrol 2005;16:1832&ndash;1838.
23.
Kielstein JT, Boger RH, Bode-Boger SM, et al: Low dialysance of asymmetric dimethylarginine (ADMA): in vivo and in vitro evidence of significant protein binding. Clin Nephrol 2004;62:295&ndash;300.
24.
Suda O, Tsutsui M, Morishita T, et al: Asymmetric dimethylarginine produces vascular lesions in endothelial nitric oxide synthase-deficient mice: involvement of renin-angiotensin system and oxidative stress. Arterioscler Thromb Vasc Biol 2004;24:1682&ndash;1688.
25.
Yilmaz MI, Saglam M, Caglar K, et al: Endothelial functions improve with decrease in asymmetric dimethylarginine (ADMA) levels after renal transplantation. Transplantation 2005;80:1660&ndash;1666.
26.
Stuhlinger MC, Tsao PS, Her JH, et al: Homocysteine impairs the nitric oxide synthase pathway: role of asymmetric dimethylarginine. Circulation 2001;104:2569&ndash;2575.
27.
Scholze A, Rinder C, Beige J, et al: Acetylcysteine reduces plasma homocysteine concentration and improves pulse pressure and endothelial function in patients with end-stage renal failure. Circulation 2004;109:369&ndash;374.
28.
Wilkinson IB, Megson IL, MacCallum T, et al: Acute methionine loading does not alter arterial stiffness in humans. J Cardiovasc Pharmacol 2001;37:1&ndash;5.
29.
Doshi S, McDowell I, Goodfellow J, et al: Relationship between s-adenosylmethionine, s-adenosylhomocysteine, asymmetric dimethylarginine, and endothelial function in healthy human subjects during experimental hyper- and hypohomocysteinemia. Metabolism 2005;54:351&ndash;360.
30.
McEniery CM, Yasmin, Hall IR, et al: Normal vascular aging: differential effects on wave reflection and aortic pulse wave velocity: The Anglo-Cardiff Collaborative Trial (ACCT). J Am Coll Cardiol 2005;46:1753&ndash;1760.
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