Evidence for alterations in circulating low-molecular-weight antioxidants and increased lipid peroxidation in smokers on hemodialysis.

BACKGROUND/AIM: Cardiovascular disease is the major cause of mortality in dialysis patients, accounting for about 40% of deaths in most large registries. Oxidative stress has been strongly implicated in the pathogenesis of these events. As end-stage renal disease is a state of elevated free radical activity, the aim of the present study was to investigate the negative impact of smoking in 57 male hemodialysis patients. METHODS: The patients, who were 20-85 years of age (mean age 51.0 +/- 14 years), had been on hemodialysis for at least 6 months before participating in this study. Fasting blood sampling for serum lipid, albumin, urate and lipophilic antioxidants such as tocopherols, carotenes, ascorbate and lipid peroxides was performed. RESULTS: The plasma malondialdehyde (MDA) concentration was significantly higher in hemodialysis patients who smoked compared to hemodialysis patients who were nonsmokers (1.92 +/- 0.52 vs. 1.59 +/- 0.42 nmol/ml, p = 0.006). No association was found between levels of MDA in smokers and parameters such as body mass index, serum cholesterol, serum triglycerides and smoking index. There were no significant differences in the plasma levels of uric acid, alpha-tocopherol, gamma-tocopherol, delta-tocopherol, alpha-carotene, beta-carotene and retinol between the two groups. A significantly lower level of plasma ascorbate was observed in hemodialysis patients who smoked compared to the nonsmoking hemodialysis patients or healthy controls (4.59 +/- 4.0 vs. 9.57 +/- 4.0 and 10.16 +/- 4.6 microg/ml, p < 0.05). Moreover, in smokers, the plasma levels of ascorbate were negatively correlated with the levels of plasma MDA (r = -0.43, p < 0.001) of each patient. Partial correlation analysis of the plasma levels of the measured antioxidants and the smoking index revealed a negative correlation between the plasma levels of lipid-normalized lycopene and the smoking index (r = -0.53, p < 0.05). CONCLUSION: Our data suggest that cigarette smoking further increases plasma-circulating products of lipid peroxidation, which are already increased in nonsmoking hemodialysis patients as compared to matched healthy controls. The lower plasma levels of ascorbate in hemodialysis patients who smoke suggest that these patients may be more susceptible to oxidative tissue damage caused by smoking.

Polymorphism in methylenetetrahydrofolate reductase gene: its impact on plasma homocysteine levels and carotid atherosclerosis in ESRD patients receiving hemodialysis.

The methylenetetrahydrofolate reductase (MTHFR) gene polymorphism has been shown to be associated with cardiovascular disease in healthy subjects as well as in patients with end-stage renal disease (ESRD). In this study, we examined the allelic frequency and genotype distribution of the MTHFR gene in 151 Chinese ESRD patients receiving hemodialysis and 135 healthy controls. In addition, we investigated the relationship between the MTHFR gene polymorphism and the plasma homocysteine (Hcy) level as well as the intima-media thickness of common carotid artery (CC-IMT) in these patients. The allelic frequency of the MTHFR gene with the C677T mutation in ESRD patients was 24.5% and that in healthy controls was 23%. Mean plasma Hcy level of the ESRD patients (23.1 +/- 7.4 micromol/l) was significantly higher than that of the controls (10.1 +/- 5.0 micromol/l), but did not correlate with vitamin B(6) and vitamin B(12) status. Moreover, the extent of hyperhomocysteinemia was genetically affected by the C677T mutation of the MTHFR gene. The plasma Hcy levels for the patients with the CC, CT and TT genotypes of the MTHFR gene were 22.3 +/- 6.8, 22.8 +/- 7.3, and 28.3 +/- 2.8 micromol/l, respectively. In addition, we found that the patients bearing the TT genotype had the highest CC-IMT (0.93 +/- 0.07 mm), whereas the lowest values (0.79 +/- 0.13 mm) were observed in those who had the CC genotype. One-way ANOVA showed that the CC-IMT in the patients with the TT genotype was significantly greater than that of the patients with the CC genotype (p < 0.05). Moreover, the mean CC-IMT of the patients carrying either TT or CT genotype of the MTHFR gene was significantly higher than that of the patients bearing the CC genotype (0.86 +/- 0.14 vs. 0.79 +/- 0.13 mm, p = 0.002). Multiple regression analysis, in which the change in CC-IMT was used as the dependent variables, identified age, smoking, the MTHFR genotype (CC = 0, CT = 1, TT = 2) and diabetes mellitus as the independent variables significantly associated with the increase of CC-IMT (p < 0.001). These risk factors jointly explained 43.9% of the CC-IMT variation and age explained most of the variation (R(2) = 0.34). We conclude that both the TT genotype and the T allele of the MTHFR gene are associated with the increase of CC-IMT in hemodialysis patients. The C677T mutation of the MTHFR gene may be an independent risk factor that predicts the development of carotid atherosclerosis in ESRD patients.