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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter / Tate, Jillian R.

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Elevated levels of Nɛ-homocysteinyl-lysine isopeptide in patients on long-term hemodialysis

Marek Kolarz1 / Rafał Głowacki2 / Tomasz Stompór3 / Janusz Wyroślak4 / 5

1Avitum Poland, Hemodialysis Unit Miechow, Miechow, Poland

2Department of Environmental Chemistry, University of Lodz, Lodz, Poland

3Department of Nephrology, Hypertension and Internal Medicine, University of Warmia and Mazury, Olsztyn, Poland

4Avitum Poland, Hemodialysis Unit Zgierz, Zgierz, Poland

5Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland

Corresponding author: Anetta Undas MD, PhD, Institute of Cardiology, Jagiellonian University Medical College, 80 Pradnicka St. 31-202 Krakow, Poland Phone: +48 12 6143004, Fax: +48 12 4233900

Citation Information: Clinical Chemistry and Laboratory Medicine. Volume 50, Issue 8, Pages 1373–1378, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: 10.1515/cclm-2011-0716, February 2012

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Background: Nɛ-homocysteinyl-lysine (Nɛ-Hcy-Lys), a product of proteolysis of Nɛ-homocysteinylated proteins, has been discovered recently. We sought to investigate the presence of Nɛ-Hcy-Lys in patients on long-term hemodialysis (HD) and its association with markers involved in atherosclerotic vascular disease.

Methods: We studied 86 patients on long-term (median, 45 months) HD and 95 apparently healthy controls. Nɛ-Hcy-Lys and total homocysteine (tHcy) were assayed using high-performance liquid chromatography. Paraoxonase 1 (PON1), asymmetric dimethylarginine (ADMA), folate, 8-isoprostaglandin F(8-iso-PGF), plasminogen activator inhibitor-1 (PAI-1), C-reactive protein (CRP), together with antibodies against Nɛ-homocysteinylated albumin and hemoglobin, were also measured.

Results: Nɛ-Hcy-Lys was detected in 15 HD patients (17.4%). Those patients had 3.1-times lower PON1 (p<0.0001), 20% higher ADMA (p<0.0001), 30% higher PAI-1 (p<0.0001), 10% lower total cholesterol (p=0.001) and LDL-cholesterol (p<0.0001), together with 20% lower triglycerides (p<0.0001) compared with subjects without measurable Nɛ-Hcy-Lys. Nɛ-Hcy-Lys levels correlated with PON1 (r=–0.62, p<0.0001), ADMA (r=0.58, p<0.0001) and PAI-1 (r=0.59, p<0.0001). Folic acid supplementation, tHcy, folate, autoimmune response to Nɛ-Hcy-proteins, and oxidative stress were not associated with the presence of Nɛ-Hcy-Lys. PON1 is the only independent predictor of the presence of Nɛ-Hcy-Lys in HD patients. None of controls had measurable Nɛ-Hcy-Lys in serum.

Conclusion: The presence of Nɛ-Hcy-Lys in HD patients is relatively infrequent and associated with lipid profile, endothelial dysfunction and impaired fibrinolysis, regardless of tHcy and folate levels.

Keywords: chronic kidney disease; hemodialysis; homocysteine; homocysteine thiolactone; Nɛ-homocysteinyl-lysine; protein homocysteinylation

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