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Clinical Chemistry and Laboratory Medicine (CCLM)

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

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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 Kolarz
  • Avitum Poland, Hemodialysis Unit Miechow, Miechow, Poland
/ Rafał Głowacki
  • Department of Environmental Chemistry, University of Lodz, Lodz, Poland
/ Tomasz Stompór
  • Department of Nephrology, Hypertension and Internal Medicine, University of Warmia and Mazury, Olsztyn, Poland
/ Janusz Wyroślak
  • Avitum Poland, Hemodialysis Unit Zgierz, Zgierz, Poland
/ Anetta Undas
  • Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland
  • :
Published Online: 2012-02-11 | DOI: https://doi.org/10.1515/cclm-2011-0716

Abstract

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

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


Received: 2011-10-02

Accepted: 2012-01-06

Published Online: 2012-02-11

Published in Print: 2012-08-01


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

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