Nephrol Dial Transplant (1996) 11: 2449-2452
© 1996 European Renal Association-European Dialysis and Transplant Association
research-article
Concentration of dimethyl-L-arginine in the plasma of patients with end-stage renal failure
1Department of Pharmacology and Clinical Pharmacology, St George's Hospital Medical School London 2Centre for Clinical Pharmacology, Cruciform Project, University College London Medical School London 3Department of Intrernal Medicine, Ruperto Carola University Heidelberg, Germany
Correspondence and offprint requests to: Correspondence and offprint requests to: R. J. MacAllister, Department of Pharmacology and Clinical Pharmacology, St Georges Hospital Medical School, London, UK
Abstract. NGNGdimethyl-L-arginine (asymmetric dimethyl-L-arginine ADMA) and NGNG dimethyl-L-arginine (symmetric dimethyl-L-arginine; SDMA) are naturally occurring analogues of L-arginine, the substrate for nitric oxide (NO) synthesis. ADMA is a potent inhibitor of NO synthesis, and accumulates in the plasma of patients with renal failure. However the precise concentration of ADMA and SDMA in renal patients is still controversial. This study was performed to measure plasma ADMA and SDMA concentrations by two different HPLC techniques in nine healthy controls and 10 uraemic subjects, and to investigate the effects of haemodialysis. In controls, the mean (±SEM) plasma concentrations of ADMA and SDMA were 0.36±0.09 and 0.39±0.05 µmol/l respectively, yielding an ADMA/SDMA ratio of 1.2± 0.17. In uraemic patients, the plasma concentrations of ADMA and SDMA were 0.9±0.08 µmol/l (P<0.001 compared to controls) and 3.4±0.3 µmol/l (P<0.001 compared to controls) with an ADMA/SDMA ratio of 0.27±0.015 (P<0.001). In the course of one 4 h haemodialysis session, ADMA concentrations decreased from 0.99±0.13 to 0.77±0.3 µmol/l and SDMA concentrations from 3.38±0.44 to 2.27±0.21 µmol/l. The plasma ADMA/creatinine ratio tended to increase from 1.26±0.20 x 10–3 to 2.01±0.41 x 10–3 It is concluded that there is a modest (3-fold) but definite increase in plasma ADMA concentration in uraemic patients compared to controls. SDMA accumulates to a greater degree (8-fold increase) and more closely parallels creatinine concentration than ADMA. The change in the ADMA/SDMA ratio is not accounted for by greater renal or dialysis clearance of ADMA, and, even though alternative explanations are not excluded, greater metabolism of ADMA than SDMA is the most likely explanation. Although small in magnitude, the increase in ADMA concentration might be biologically significant.
Keywords: uraemia; dialysis; NO synthase; ADMA; SDMA
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Turiel, F. Atzeni, L. Tomasoni, S. de Portu, L. Delfino, B. D. Bodini, M. Longhi, S. Sitia, M. Bianchi, P. Ferrario, et al. Non-invasive assessment of coronary flow reserve and ADMA levels: a case-control study of early rheumatoid arthritis patients Rheumatology, July 1, 2009; 48(7): 834 - 839. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Sharma, Z. Zhou, H. Miura, A. Papapetropoulos, E. T. McCarthy, R. Sharma, V. J. Savin, and E. A. Lianos ADMA injures the glomerular filtration barrier: role of nitric oxide and superoxide Am J Physiol Renal Physiol, June 1, 2009; 296(6): F1386 - F1395. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Baylis Nitric oxide deficiency in chronic kidney disease Am J Physiol Renal Physiol, January 1, 2008; 294(1): F1 - F9. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Tatematsu, S. Wakino, T. Kanda, K. Homma, K. Yoshioka, K. Hasegawa, N. Sugano, M. Kimoto, T. Saruta, and K. Hayashi Role of Nitric Oxide-Producing and -Degrading Pathways in Coronary Endothelial Dysfunction in Chronic Kidney Disease J. Am. Soc. Nephrol., March 1, 2007; 18(3): 741 - 749. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Bulau, D. Zakrzewicz, K. Kitowska, J. Leiper, A. Gunther, F. Grimminger, and O. Eickelberg Analysis of methylarginine metabolism in the cardiovascular system identifies the lung as a major source of ADMA Am J Physiol Lung Cell Mol Physiol, January 1, 2007; 292(1): L18 - L24. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Amann, C. Wanner, and E. Ritz Cross-Talk between the Kidney and the Cardiovascular System J. Am. Soc. Nephrol., August 1, 2006; 17(8): 2112 - 2119. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Morimoto, K. Nakao, K. Fukuoka, A. Sarai, A. Yano, T. Kihara, S. Fukuda, J. Wada, and H. Makino Long-term use of vitamin E-coated polysulfone membrane reduces oxidative stress markers in haemodialysis patients Nephrol. Dial. Transplant., December 1, 2005; 20(12): 2775 - 2782. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. T. Chan, P. J. Harvey, R. Boger, A. Pierratos, and J. S. Floras Letter to the Editor: Dissociation Between the Short-Term Effects of Nocturnal Hemodialysis on Endothelium Dependent Vasodilation and Plasma ADMA Arterioscler Thromb Vasc Biol, December 1, 2005; 25(12): 2685 - 2686. [Full Text] [PDF]
|
|
|
|
 |
|
 R. Schnabel, S. Blankenberg, E. Lubos, K. J. Lackner, H. J. Rupprecht, C. Espinola-Klein, N. Jachmann, F. Post, D. Peetz, C. Bickel, et al. Asymmetric Dimethylarginine and the Risk of Cardiovascular Events and Death in Patients With Coronary Artery Disease: Results from the AtheroGene Study Circ. Res., September 2, 2005; 97(5): e53 - e59. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Fliser, F. Kronenberg, J. T. Kielstein, C. Morath, S. M. Bode-Boger, H. Haller, and E. Ritz Asymmetric Dimethylarginine and Progression of Chronic Kidney Disease: The Mild to Moderate Kidney Disease Study J. Am. Soc. Nephrol., August 1, 2005; 16(8): 2456 - 2461. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Nijveldt, T. Teerlink, M. P. C. Siroen, B. van der Hoven, H. A. Prins, M. J. Wiezer, C. Meijer, J. R. M. van der Sijp, M. A. Cuesta, S. Meijer, et al. Elevation of Asymmetric Dimethylarginine (ADMA) in Patients Developing Hepatic Failure After Major Hepatectomy JPEN J Parenter Enteral Nutr, November 1, 2004; 28(6): 382 - 387. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. F. Perna, D. Ingrosso, E. Satta, C. Lombardi, P. Galletti, A. D'Aniello, and N. G. De Santo Plasma Protein Aspartyl Damage Is Increased in Hemodialysis Patients: Studies on Causes and Consequences J. Am. Soc. Nephrol., October 1, 2004; 15(10): 2747 - 2754. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Vallance and J. Leiper Cardiovascular Biology of the Asymmetric Dimethylarginine:Dimethylarginine Dimethylaminohydrolase Pathway Arterioscler Thromb Vasc Biol, June 1, 2004; 24(6): 1023 - 1030. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Tarnow, P. Hovind, T. Teerlink, C. D.A. Stehouwer, and H.-H. Parving Elevated Plasma Asymmetric Dimethylarginine as a Marker of Cardiovascular Morbidity in Early Diabetic Nephropathy in Type 1 Diabetes Diabetes Care, March 1, 2004; 27(3): 765 - 769. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Nijveldt, T. Teerlink, C. van Guldener, H. A. Prins, A. A. van Lambalgen, C. D. A. Stehouwer, J. A. Rauwerda, and P. A. M. van Leeuwen Handling of asymmetrical dimethylarginine and symmetrical dimethylarginine by the rat kidney under basal conditions and during endotoxaemia Nephrol. Dial. Transplant., December 1, 2003; 18(12): 2542 - 2550. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. H Boger The emerging role of asymmetric dimethylarginine as a novel cardiovascular risk factor Cardiovasc Res, October 1, 2003; 59(4): 824 - 833. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Toda and T. Okamura The Pharmacology of Nitric Oxide in the Peripheral Nervous System of Blood Vessels Pharmacol. Rev., June 1, 2003; 55(2): 271 - 324. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Amann, C. Ritz, M. Adamczak, and E. Ritz Why is coronary heart disease of uraemic patients so frequent and so devastating? Nephrol. Dial. Transplant., April 1, 2003; 18(4): 631 - 640. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Paiva, J. Laakso, H. Laine, R. Laaksonen, J. Knuuti, and O. T. Raitakari Plasma asymmetric dimethylarginine and hyperemic myocardial blood flow in young subjects with borderline hypertension or familial hypercholesterolemia J. Am. Coll. Cardiol., October 2, 2002; 40(7): 1241 - 1247. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Maas, E. Schwedhelm, J. Albsmeier, and R. H Boger The pathophysiology of erectile dysfunction related to endothelial dysfunction and mediators of vascular function Vascular Medicine, August 1, 2002; 7(3): 213 - 225. [Abstract] [PDF]
|
|
|
|
 |
|
 M. C. Stuhlinger, F. Abbasi, J. W. Chu, C. Lamendola, T. L. McLaughlin, J. P. Cooke, G. M. Reaven, and P. S. Tsao Relationship Between Insulin Resistance and an Endogenous Nitric Oxide Synthase Inhibitor JAMA, March 20, 2002; 287(11): 1420 - 1426. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Zoccali, F. A. Benedetto, R. Maas, F. Mallamaci, G. Tripepi, L. Salvatore Malatino, and R. Boger Asymmetric Dimethylarginine, C-Reactive Protein, and Carotid Intima-Media Thickness in End-Stage Renal Disease J. Am. Soc. Nephrol., February 1, 2002; 13(2): 490 - 496. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. T. Kielstein, R. H. Boger, S. M. Bode-Boger, J. C. Frolich, H. Haller, E. Ritz, and D. Fliser Marked Increase of Asymmetric Dimethylarginine in Patients with Incipient Primary Chronic Renal Disease J. Am. Soc. Nephrol., January 1, 2002; 13(1): 170 - 176. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. T. Kielstein, J. C. Frolich, H. Haller, and D. Fliser ADMA (asymmetric dimethylarginine): an atherosclerotic disease mediating agent in patients with renal disease? Nephrol. Dial. Transplant., September 1, 2001; 16(9): 1742 - 1745. [Full Text] [PDF]
|
|
|
|
 |
|
 N Wahbi, R N Dalton, C Turner, M Denton, I Abbs, and R Swaminathan Dimethylarginines in chronic renal failure J. Clin. Pathol., June 1, 2001; 54(6): 470 - 473. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A.C. Mendes Ribeiro, T.M.C. Brunini, J.C. Ellory, and G.E. Mann Abnormalities in L-arginine transport and nitric oxide biosynthesis in chronic renal and heart failure Cardiovasc Res, March 1, 2001; 49(4): 697 - 712. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Segarra, P. Medina, J. M. Vila, J. B. Martinez-Leon, R. M. Ballester, P. Lluch, and S. Lluch Contractile effects of arginine analogues on human internal thoracic and radial arteries J. Thorac. Cardiovasc. Surg., October 1, 2000; 120(4): 729 - 736. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Amann and E. Ritz Microvascular disease--the Cinderella of uraemic heart disease Nephrol. Dial. Transplant., October 1, 2000; 15(10): 1493 - 1503. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Cooke Does ADMA Cause Endothelial Dysfunction? Arterioscler Thromb Vasc Biol, September 1, 2000; 20(9): 2032 - 2037. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Kalliovalkama, P. Jolma, J.-P. Tolvanen, M. Kahonen, N. Hutri-Kahonen, H. Saha, S. Tuorila, E. Moilanen, and I. Porsti Potassium channel-mediated vasorelaxation is impaired in experimental renal failure Am J Physiol Heart Circ Physiol, October 1, 1999; 277(4): H1622 - H1629. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Segarra, P. Medina, R. M. Ballester, P. Lluch, M. Aldasoro, J. M. Vila, S. Lluch, and D. A. Pelligrino Effects of Some Guanidino Compounds on Human Cerebral Arteries • Editorial Comment Stroke, October 1, 1999; 30(10): 2206 - 2211. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Leiper and P. Vallance Biological significance of endogenous methylarginines that inhibit nitric oxide synthases Cardiovasc Res, August 15, 1999; 43(3): 542 - 548. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. VANHOLDER and R. DE SMET Pathophysiologic Effects of Uremic Retention Solutes J. Am. Soc. Nephrol., August 1, 1999; 10(8): 1815 - 1823. [Full Text]
|
|
|
|
|
|
R. Wever, P. Boer, M. Hijmering, E. Stroes, M. Verhaar, J. Kastelein, K. Versluis, F. Lagerwerf, H. van Rijn, H. Koomans, et al. Nitric Oxide Production Is Reduced in Patients With Chronic Renal Failure Arterioscler Thromb Vasc Biol, May 1, 1999; 19(5): 1168 - 1172. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Miyazaki, H. Matsuoka, J. P. Cooke, M. Usui, S. Ueda, S. Okuda, and T. Imaizumi Endogenous Nitric Oxide Synthase Inhibitor : A Novel Marker of Atherosclerosis Circulation, March 9, 1999; 99(9): 1141 - 1146. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. T. KIELSTEIN, R. H. BÖGER, S. M. BODE-BÖGER, J. SCHÄFFER, M. BARBEY, K. M. KOCH, and J. C. FRÖLICH Asymmetric Dimethylarginine Plasma Concentrations Differ in Patients with End-Stage Renal Disease: Relationship to Treatment Method andAtherosclerotic Disease J. Am. Soc. Nephrol., March 1, 1999; 10(3): 594 - 600. [Abstract] [Full Text]
|
|