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 F2α(8-iso-PGF2α), 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.