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Licensed Unlicensed Requires Authentication Published by De Gruyter February 11, 2012

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

  • Marek Kolarz , Rafał Głowacki , Tomasz Stompór , Janusz Wyroślak and Anetta Undas EMAIL logo

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.


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: 2011-10-2
Accepted: 2012-1-6
Published Online: 2012-02-11
Published in Print: 2012-08-01

©2012 by Walter de Gruyter Berlin Boston

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