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

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. CONCLUSION: 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.

Antibodies against N-homocysteinylated proteins and their determinants in patients on long-term hemodialysis.

INTRODUCTION: The factors that determine the level of antibodies against N-homocysteinylated (N-Hcy) proteins have not been established so far. The clinical significance of these antibodies and their effect on cardiovascular (CV) risk in patients with end-stage renal disease (ESRD) are still unknown. OBJECTIVES: The aim of this study was to identify the factors that determine the level of antibodies against N-Hcyalbumin and N-Hcy hemoglobin in patients on long-term hemodialysis (HD). PATIENTS AND METHODS: The study involved 247 subjects on long-term HD (110 women, 137 men; age range, 23-89 years) and 60 controls matched for age, sex, and CV risk factors (serum creatinine level <140 micromol/l). Serum antibodies against N-Hcyalbumin and N-Hcyhemoglobin were determined using an in-house enzyme-linked immunosorbent assay. Total homocysteine (tHcy), folate, and 8-isoprostaglandin F2alpha (8-iso-PGF(2alpha)) were also measured. RESULTS: Patients on HD had higher serum levels of anti-N-Hcy-albumin (absorbancy at 490 nm: 0.56 [0.49-0.623] vs. 0.259 [0.198-0.338], P <0.0001) and anti-N-Hcy-hemoglobin antibodies (0.659 [0.597-0.723] vs. 0.379 [0.289-0.442], P <0.0001) as compared with controls. The level of both antibodies correlated with tHcy (r = 0.56, P <0.0001 and r = 0.67, P <0.0001, respectively), 8-iso-PGF(2alpha) (r = 0.48, P <0.0001 and r = 0.63, P <0.0001, respectively), and folate (r = -0.18, P = 0.0054 and r = -0.38, P <0.0001, respectively), but not with HD duration, the initial cause of ESRD, and CV comorbidity. CONCLUSIONS: In HD patients, tHcy is an independent predictor of antibodies against N-Hcy proteins. Folate and 8-iso-PGF(2alpha) concentrations were not independently associated with the levels of both antibodies.

[The relation between plasma leptin concentration and body fat mass in patients with rheumatoid arthritis]. / Zaleznosc pomiedzy stezeniem leptyny w surowicy krwi a masa tkanki tluszczowej u chorych na reumatoidalne zapalenie stawów.

The prospective, cross-sectional study was undertaken to evaluate the relation between the fat mass and serum leptin level in patients with rheumatoid arthritis (RA). Low body mass and anorexia are commonly found in patients with RA. Inflammatory cytokines may significantly influence the secretion of anorectic hormone--leptin--that was confirmed in both experimental and clinical studies. Fifty-two non-diabetic and non-obese patients (38 females, 14 males) were studied. Mean age was 56 +/- 11 years and mean body mass index (BMI) 24.6 +/- 4.1 kg/m2. The disease activity score (DAS) was 3.9 +/- 1.4; range 1.4-7.4, and disease duration 8.1 +/- 6.7 years. Serum leptin was measured by ELISA and body composition by double X-ray densitometry. Mean serum leptin concentration was 2.8 +/- 1.4 ng/ml in patients with RA was lower than in the control group (4.2 +/- 2.0). In a simple regression analysis leptin did not correlate with BMI (R Spearman = 0.01), C-reactive protein (R = 0.08), total fat mass (R = 0.08), trunk fat (R = 0.05), limbs fat (R = 0.09) and DAS (R = -0.17). This relation was also not influenced by gender or type of immunosuppressive therapy. In a multiple regression model none of the independent variables explained the significant portion of variance of serum leptin. It is concluded that the physiologic relation of serum leptin to body fat stores is not present in patients with RA.