title: Elevated levels of Nε-homocysteinyl-lysine isopeptide in patients on long-term hemodialysis.
abstract: BACKGROUND
  Nε-homocysteinyl-lysine (Nε-Hcy-Lys), a product of proteolysis of Nε-homocysteinylated proteins, has been discovered recently. We sought to investigate the presence of Nε-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. Nε-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 Nε-homocysteinylated albumin and hemoglobin, were also measured.
  
  
  RESULTS
  Nε-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 Nε-Hcy-Lys. Nε-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 Nε-Hcy-proteins, and oxidative stress were not associated with the presence of Nε-Hcy-Lys. PON1 is the only independent predictor of the presence of Nε-Hcy-Lys in HD patients. None of controls had measurable Nε-Hcy-Lys in serum.
  
  
  CONCLUSIONS
  The presence of Nε-Hcy-Lys in HD patients is relatively infrequent and associated with lipid profile, endothelial dysfunction and impaired fibrinolysis, regardless of tHcy and folate levels.
authors.affiliation: Avitum Poland, Hemodialysis Unit Miechow, Miechow, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Kolarz
authors.forename: Rafał
authors.initials: R
authors.lastname: Głowacki
authors.forename: Tomasz
authors.initials: T
authors.lastname: Stompór
authors.forename: Janusz
authors.initials: J
authors.lastname: Wyroślak
authors.forename: Anetta
authors.initials: A
authors.lastname: Undas
mesh_terms: D000368:Aged; D000906:Antibodies / Q000097:blood; D001120:Arginine / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000097:blood; D050197:Atherosclerosis / Q000097:blood; D015415:Biomarkers / Q000097:blood; D004151:Dipeptides / Q000097:blood* / Q000276:immunology; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis
chemical_list: D000906:Antibodies; D015415:Biomarkers; D004151:Dipeptides; C556024:N(epsilon)-homocysteinyl-lysine; C487735:dimethylarginine; D001120:Arginine