Smoking is associated with alterations of blood thiol-group related antioxidants in patients on hemodialysis.

Cardiovascular disease is the major complication and cause of mortality in the dialysis population, accounting for about 40% of deaths. Oxidative stress has been strongly implicated in the pathogenesis of these events. As patients in end-stage renal disease (ESRD) are in a state of elevated free radical activity, the aim of the present study was to investigate the negative impact of smoking in 45 male hemodialysis (HD) patients. These patients, who were 40-85 years of age (mean age 60.9 +/- 13.3 years), had been on hemodialysis for at least 12 months before participating in this study. Fasting blood sampling for serum lipid, albumin, urate, lipid peroxides total blood glutathione (tGSH), non-GSH free sulfhydryl compounds (non-GSH fSH), plasma glutathione peroxidase (pGSHPx), erythrocytes glutathione peroxidase (rGSHPx), plasma glutathione S-transferase (pGST) and erythrocytes glutathione S-transferase (rGST) were determined. Our study showed that the plasma malonyldialdehyde (MDA) concentration was significantly higher in HD patients who smoked than in those who were non- smokers (1.99 +/- 0.53 vs. 1.55 +/- 0.46 nmol/ml, p = 0.008). No association was found between levels of MDA in smokers and BMI, serum cholesterol and triglycerides and smoking index. We also found that the circulating plasma levels of tGSH and non-GSH fSH was lower in the HD patients who smoked (tGSH 164.9 +/- 41.5 vs. 203.4 +/- 45.3 microg/ml; fSH 271.1 +/- 55.8 vs. 308.8 +/- 46.7 microg/ml; p < 0.05 and p < 0.001, respectively). There were no significant differences in the plasma levels of uric acid, pGSHPx, rGSHPx, pGST, rGST, albumin, and age between the 2 groups. Partial correlation analysis of the plasma levels of the measured antioxidants and the smoking index revealed a negative correlation between the plasma levels of tGSH and smoking index (r = -0.62, p < 0.003). Similarly, the plasma levels of tGSH was found negatively correlated with the levels of plasma MDA (r = -0.32, p < 0.05) of the HD patients. In conclusion, our data suggest that cigarette smoking has a negative impact on plasma-circulating products of lipid peroxidation in HD patients. The lower blood levels of the tGSH and non-GSH fSH in HD patients who smoked suggests that these patients may be more susceptible to oxidative damage caused by smoking.

8-iso-prostaglandin F2alpha as a useful clinical biomarker of oxidative stress in ESRD patients.

BACKGROUND/AIMS: Chronic renal failure is associated with elevated indices of oxidative stress. We tested the hypothesis that the in vivo formation of the F(2)-isoprostane (8-iso-prostaglandin PGF(2alpha)), a bioactive product of arachidonic acid peroxidation, is enhanced in end-stage renal disease (ESRD) patients receiving hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD). METHODS: Plasma samples were obtained from 35 HD patients, 30 CAPD patients and 30 age- and sex-matched healthy subjects for measurement of immunoreactive 8-iso-PGF(2alpha). RESULTS: Plasma 8-iso-PGF(2alpha) levels were significantly higher (p < 0.001) in HD and CAPD patients (346.3 +/- 132.4 pg/ml; range 49.8-870) than in age-matched control subjects (150.9 +/- 61.6 pg/ml; range 33.5-235). In addition, we also found that 8-iso-PGF(2alpha) concentration was significantly (p = 0.007) higher in HD patients (389.8 +/- 148.3 pg/ml) than in CAPD patients (254.3 +/- 76.6 pg/ml). Plasma 8-iso-PGF(2alpha) concentration was linearly correlated with serum haptoglobin, C-reactive protein (CRP) and plasma MDA (r = 0.58, p = 0.003; r = 0.29, p < 0.05 and r = 0.38, p < 0.05 respectively). On the other hand, plasma 8-iso-PGF(2alpha) levels were inversely associated with serum albumin and total cholesterol (r = -0.31 and r = -0.28, respectively; p < 0.05). CONCLUSIONS: We conclude that ESRD on both HD and CAPD is associated with increased formation of F(2)-isoprostanes, a correlate of enhanced lipid peroxidation. We also found that plasma 8-iso-PGF(2alpha) was casually related to some acute phase reactant proteins such as serum CRP, albumin and haptoglobin. This may provide an important biochemical link between lipid peroxidation, inflammation and accelerated atherosclerosis in the uremic milieu.