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Elevated levels of Nɛ-homocysteinyl-lysine isopeptide in patients on long-term hemodialysis
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Marek Kolarz
Published/Copyright:
February 11, 2012
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 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.
Keywords: chronic kidney disease; hemodialysis; homocysteine; homocysteine thiolactone; Nɛ-homocysteinyl-lysine; protein homocysteinylation
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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Keywords for this article
chronic kidney disease;
hemodialysis;
homocysteine;
homocysteine thiolactone;
Nɛ-homocysteinyl-lysine;
protein homocysteinylation
Articles in the same Issue
- Masthead
- Masthead
- Editorial
- EDTA-dependent pseudothrombocytopenia: further insights and recommendations for prevention of a clinically threatening artifact
- Reviews
- Mitochondria as sources and targets of damage in cellular aging
- Application of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) in Alzheimer’s disease
- Opinion Papers
- The intellectual contribution of laboratory medicine professionals to research papers on laboratory medicine topics published in high-impact general medicine journals
- Laboratory medicine and sports: between Scylla and Charybdis
- Guidelines and Recommendations
- The EC4 European Syllabus for Post-Graduate Training in Clinical Chemistry and Laboratory Medicine: version 4 – 2012
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- Assessing the utility of whole genome amplified DNA as a template for DMET Plus array
- General Clinical Chemistry And Laboratory Medicine
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- The transferrin/log(ferritin) ratio: a new tool for the diagnosis of iron deficiency anemia
- Instructions on laboratory monitoring in 200 drug labels
- Lipid peroxidation markers in Crohn’s disease: the associations and diagnostic value
- Impact of asthmatic control status on serum cystatin C concentrations
- Elevated levels of Nɛ-homocysteinyl-lysine isopeptide in patients on long-term hemodialysis
- Interleukin-1α gene variants influence bone mineral density and the risk of osteoporotic hip fractures in elderly Slovenian people
- Novel method to dissociate platelet clumps in EDTA-dependent pseudothrombocytopenia based on the pathophysiological mechanism
- Proficiency testing/external quality assurance for the PFA-100®
- Interference of selected flavonoid aglycons in platelet aggregation assays
- Infectious Diseases
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- Association between ischemia-modified albumin, homocysteine, vitamin B12 and folic acid in patients with severe sepsis
- Evidence for serum miR-15a and miR-16 levels as biomarkers that distinguish sepsis from systemic inflammatory response syndrome in human subjects
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- Cardiovascular Diseases
- Reactive oxygen metabolites (ROMs) are associated with cardiovascular disease in chronic hemodialysis patients
- Methylenetetrahydrofolate reductase C677T and reduced folate carrier 80 G>A polymorphisms are associated with an increased risk of conotruncal heart defects
- Oxidative stress as a predictor of cardiovascular events in coronary artery disease patients
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