***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Neutrophil oxygen radical production is increased in end-stage renal disease ( ESRD ) patients and it is further enhanced during dialysis with low-flux cellulosic membranes . This increased oxygen radical production may contribute to the protein and lipid oxidation observed in ESRD patients . We tested the hypothesis that high-flux hemodialysis does not increase oxygen radical production and that it is not associated with protein oxidation . METHODS Neutrophil oxygen radical production was measured during dialysis with high-flux dialyzers containing polysulfone and cellulose triacetate membranes . Free sulfhydryl and carbonyl groups and advanced oxidation protein products were measured to assess plasma protein oxidation . RESULTS Pre-dialysis , neutrophil oxygen radical production was significantly greater than normal and increased significantly as blood passed through the dialyzer in the first 30 minutes of dialysis . Post-dialysis , however , neutrophil oxygen radical production had decreased and was not different from normal . Pre-dialysis , significant plasma protein oxidation was evident from reduced free sulfhydryl groups , increased carbonyl groups , and increased advanced oxidation protein products . Post-dialysis , plasma protein free sulfhydryl groups had increased to normal levels , while plasma protein carbonyl groups increased slightly , and advanced oxidation protein products remained unchanged . CONCLUSIONS The results of this study show that neutrophil oxygen radical production normalizes during high-flux dialysis , despite a transient increase early in dialysis . This decrease in oxygen radical production is associated with an improvement in some , but not all , measures of protein oxidation Red blood cells and plasma reduced and oxidized glutathione levels , glutathione peroxidase ( GSH-Px ) activity , thiobarbituric acid reactants ( TBAR ) of both chronic ambulatory peritoneal dialysis ( CAPD ) patients and a matched control group were investigated in this study . Oxidized and reduced pyridinic nucleotides in red blood cells ( RBC ) , in which NADPH is a direct expression of hexose monophosphate shunt function , were also studied . The results obtained indicate that RBC and plasma are exposed to oxidative stress in CAPD . This condition is characterized by a decreased GSH/GSSG ratio , particularly evident in RBC as a consequence of the GSSG accumulation . Lipid peroxidation is increased , as indicated by raised TBAR levels , and reduced pyridinic nucleotides are decreased . Increased GSH-Px levels and unmodified or slightly increased GSH content were observed in the RBC but not in plasma , which showed decreased GSH and unmodified peroxidase activity . Peroxidase correlated positively with TBAR levels in the RBC lysates . In a subgroup of patients treated with erythropoietin ( vs. untreated patients and controls ) no differences were observed in the glutathione-related parameters studied . These data suggest that a mechanism for adaptation to oxidative conditions may be present in CAPD and its effects on RBC integrity are discussed in comparison with the hemodialysis conditions previously studied Increased markers of oxidative stress and acute-phase inflammation are prevalent in patients undergoing maintenance hemodialysis therapy ( MHD ) , and are associated with increased mortality and hospitalization rates and decreased erythropoietin responsiveness . No adequately powered studies have examined the efficacy of antioxidant therapies on markers of inflammation and oxidative stress . We tested the hypothesis that oral antioxidant therapy over 6 months would decrease selected biomarkers of acute-phase inflammation and oxidative stress and improve erythropoietic response in prevalent MHD patients . In total , 353 patients were enrolled in a prospect i ve , placebo-controlled , double-blind clinical trial and r and omly assigned to receive a combination of mixed tocopherols ( 666 IU/d ) plus α-lipoic acid ( ALA ; 600 mg/d ) or matching placebos for 6 months ( NCT00237718 ) ; 238 patients completed the study . High-sensitivity C-reactive protein ( hsCRP ) and IL-6 concentration were measured as biomarkers of systemic inflammation , and F2 isoprostanes and isofurans were measured as biomarkers of oxidative stress . The groups did not significantly differ at baseline . At 3 and 6 months , the treatment had no significant effect on plasma hsCRP , IL-6 , F2 isoprostane , or isofuran concentrations and did not improve the erythropoietic response . No major adverse events were related to the study drug , and both groups had similar mortality and hospitalization rates during the study . In conclusion , the administration of mixed tocopherols and ALA was generally safe and well tolerated , but did not influence biomarkers of inflammation and oxidative stress or the erythropoietic response BACKGROUND Erythrocytes represent an important component of the antioxidant capacity of blood , comprising , in particular , intracellular enzymes , including platelet-activating factor acetylhydrolase ( PAF-AH ) and glutathione peroxidase ( Gpx ) . We evaluated the erythrocyte PAF-AH and Gpx activities in various stages of chronic kidney disease ( CKD ) , and further investigated whether erythropoietin ( EPO ) administration in these patients has any influence on the enzyme activities . METHODS Thirty-six patients ( 19 men and 17 women ) with CKD ( stages 1 to 5 ) participated in the study . Thirteen of them presented with CKD stage 1 to 2 ( group I ) , whereas 23 patients presented with CKD stage 3 to 5 and r and omized into two groups ( i.e. , groups II and III ) . Patients of group II ( N= 11 ) were administered EPO subcutaneously , 50 units per kg once per week . In group III ( N= 12 ) , EPO was initiated only when the hemoglobin ( Hb ) levels decreased during follow-up to less than 9 g/dL. All patients were seen on an outpatient basis at 2 and 4 months . Fifteen normolipidemic age- and sex-matched healthy volunteers also participated in the study and were used as controls . The PAF-AH and Gpx activities were determined in isolated washed erythrocytes . RESULTS The erythrocyte-associated PAF-AH and Gpx activities were higher in all CKD patient groups at baseline compared to controls , the groups II and III exhibiting significantly higher enzyme activities compared with group I. In all studied population s , both enzyme activities were negatively correlated with the creatinine clearance values . Importantly , the PAF-AH and Gpx activities were progressively decreased during the follow-up in patients not treated with EPO ( group III ) , a phenomenon not observed in patients receiving EPO ( group II ) , or in patients of group I. This reduction in enzyme activities was positively correlated with the decrease in the creatinine clearance values in patients of group III . CONCLUSION Significant alterations in the erythrocyte-associated PAF-AH and Gpx activities related to the disease stage are observed in CKD patients . Administration of EPO prevented the reduction in enzyme activities observed during the progression of the renal insufficiency , thus preserving the erythrocyte defense mechanisms against oxidative stress BACKGROUND Lipid peroxidation may be important in the pathogenesis of atherosclerosis , particularly in its earliest stages . Evidence predominantly from in vitro studies suggests that antioxidant vitamins can prevent lipid peroxidation and that vitamin C and vitamin E have synergistic effects . However , in vivo evidence in support of these hypotheses is sparse . OBJECTIVE The objective was to determine the effects of vitamin C and vitamin E , alone or in combination , on in vivo lipid peroxidation . DESIGN We conducted a placebo-controlled , 2 x 2 factorial trial of vitamin C ( 500 mg ascorbate/d ) and vitamin E ( 400 IU RRR-alpha-tocopheryl acetate/d ) supplementation in 184 nonsmokers . The mean duration of supplementation was 2 mo . The outcome measures were changes from baseline in urinary 8-iso-prostagl and in F(2alpha ) , urinary malondialdehyde + 4-hydroxyalkenals , and serum oxygen-radical absorbance capacity . RESULTS The within-group mean changes ( and 95 % CIs ) in urinary 8-iso-prostagl and in F(2alpha ) ( pg/mg creatinine ) were 9.0 ( -125.1 , 143.1 ) , -150.0 ( -275.4 , -24.6 ) , -141.3 ( -230.5 , -52.1 ) , and -112.5 ( -234.8 , 9.8 ) in the placebo , vitamin C alone , vitamin E alone , and vitamins C + E groups , respectively . No synergistic effect of these 2 vitamins on urinary 8-iso-prostagl and in F(2alpha ) was observed ( P = 0.12 ) . Neither vitamin had an effect on urinary malondialdehyde + 4-hydroxyalkenals .  Vitamin C , but not vitamin E , increased serum oxygen-radical absorbance capacity ( P = 0.01 ) . CONCLUSIONS Supplementation with vitamin C or vitamin E alone reduced lipid peroxidation to a similar extent . Supplementation with a combination of vitamins C and E conferred no benefit beyond that of either vitamin alone It has been suggested that hemodialysis patients may be under increased oxidative stress and may therefore benefit from the long-term use of antioxidants ( particularly for the reduction of the risk of heart disease ) . The aim of this study was , first , to evaluate the effect of hemodialysis by itself on lipid and lipoprotein oxidation profiles and , second , to analyze the effect of vitamin C supplementation in patients with end-stage renal disease starting hemodialysis . Forty-one patients with end-stage renal disease were enrolled and r and omized to receive 1000 mg/d vitamin C or matching placebo before starting hemodialysis . We measured lipid profile and the susceptibility of low-density lipoprotein ( LDL ) and high-density lipoprotein ( HDL ) to oxidation using copper ions at the moment of inclusion and after 1 year . All lipoperoxidation parameters were included . Hemodialysis by itself improved the lipid profile , lowering total cholesterol ( 176.4 + /- 48.4 to 154.2 + /- 28.8 mg/dL , P < .01 ) , LDL cholesterol ( 94.1 + /- 39.6 to 76.1 + /- 26.6 mg/dL LDL , P < .03 ) , and phospholipids levels ( 196.5 + /- 36.7 to 182.9 + /- 36.1 mg/dL , P < .05 ) in all patients on maintenance hemodialysis . The HDL cholesterol was also decreased ( 49.4 + /- 19.8 to 43.4 + /- 24.1 mg/dL HDL , P < .03 ) . No significant differences were detected between patients receiving vitamin C and those receiving placebo . Thiobarbituric acid reactive substances ( TBARS ) and lipoperoxides increased in patients after a year of hemodialysis , but the difference was lower in those administered vitamin C for a year-TBARS LDL ( in nanograms per gram LDL ) : 0.25 + /- 0.20 to 0.38 + /- 0.2 in vitamin C-treated subjects and 0.28 + /- 0.17 to 0.46 + /- 0.21 in those treated with placebo ( P < .007 ) ; TBARS HDL ( in nanograms per gram HDL ) : 0.22 + /- 0.12 to 0.34 + /- 0.30 in patients receiving vitamin C and 0.20 + /- 0.18 to 0.28 + /- 0.19 in those receiving placebo ( P = .071 ) . Hemodialysis by itself seems to improve the lipid profile in patients with a previous prooxidative state such as uremia . Although our results failed to demonstrate significant differences between vitamin C-treated and untreated patients , and despite the small number of patients , the trend toward a decrease in oxidation products due to vitamin C supplementation may be beneficial for oxidation parameters . This area remains controversial and under active investigation . Further research is necessary before a firm conclusion can be reached In the last few years haemodiafiltration with on-line regeneration of ultrafiltrate ( HFR ) has been shown to have a positive impact on inflammation and oxidative stress biomarkers , but its effect on antioxidant levels and on oxidative damage to biomolecules in the long-term is still unknown . This is a r and omised clinical study over 12 months involving 40 patients on haemodialysis , comparing the effect of HFR ( n = 25 ) dialysis with haemodialysis with polysulfone ( HD-PS , n = 15 ) on oxidative stress . Total antioxidant capacity , enzymatic antioxidant [ superoxide dismutase ( SOD ) , catalase and glutathione peroxidase ] , non-enzymatic ( GSH ) and biomarkers of oxidative stress ( TBARs , carbonyl groups and 8-OH-dG ) were evaluated . The antioxidant activity decreased in the lymphocytes of patients dialysed with HFR , with a significant decrease in the 
    Output:
    
Even from an early stage , imbalance in redox status is evident and as the kidney function worsens it becomes more profound .
Hemodialysis therapy per se seems to negatively influence the redox status by the elevation of lipid peroxidation markers , protein carbonylation , and impairing erythrocyte antioxidant defense .
However , other dialysis modalities do not so far appear to confer advantages .
Supplementation with antioxidants might assist and should be considered as an early intervention to halt premature atherogenesis development at an early stage of CKD