Why Hemodialysis Patients Are in a Prooxidant State? What Could Be Done to Correct the Pro/Antioxidant Imbalance (original) (raw)
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Effect of Hemodialysis on the Oxidative Stress and Antioxidants
Clinical Chemistry and Laboratory Medicine, 2002
Oxidative stress plays a role in many disease states. These diseases have an increased incidence in uremia, and particularly in hemodialysis (HD) patients. This suggests an increased exposure to oxidative stress. An imbalance between oxidants and antioxidants has been suggested in uremic patients on HD. However, the respective influence of uremia and dialysis procedure has not been evaluated. It is postulated that antioxidant capacity in uremic patients is reduced, yet the mechanism remains unclear. We have determined the levels of lipid peroxidation expressed as thiobarbituric acid-reactive substances. We assessed oxidative protein damage by carbonyl content and activities of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in predialysis uremic patients and in end-stage renal disease (ESRD) patients before and after hemodialysis. Vitamin E and vitamin C levels, reduced glutathione and sulfhydryl content were also studied. We found enhanced oxidative stress in ESRD patients undergoing HD and in predialysis uremic patients. This was mostly due to defective antioxidant enzyme levels. Preventive modalities, including use of biocompatible membranes, ultrapure dialysate, exogenous supplementation of antioxidant vitamins, extracorporeal removal of reactive oxygen species (ROS) and oxidatively modified substances, would appear highly desirable to reduce complications in the long-term dialysis patients.
Cardiovascular diseases are the leading cause of death in patients who undergo regular hemodialysis. Oxidative stress is a non-traditional risk factor for the development of cardiovascular diseases in this population of patients. It is defined as tissue damage caused by balance disturbance between the formation of free radicals and the function of protective antioxidative systems. The superoxide anion and hydrogen peroxide are precursors in the formation of stronger oxidants, such as: hydroxyl radical, peroxynitrite and hypochloric acid. Superoxide dismutase is the first line of antioxidant protection while catalase, glutathione peroxidase, trace elements, vitamin C, vitamin E, N-acetylcysteine and coenzyme Q10 also have a significant antioxidative role. Hemodialysis is itself a trigger for the increased formation of oxygen free radicals. The two main pathophysiological mechanisms of the increased formation of free oxygen radicals during the hemodialysis session are: bionicompatibility of the dialysis membrane and the presence of endotoxins in the hemodialysis solution. The measurement of myeloperoxidase concentration in a patient's serum during hemodialysis is an indicator of the severity of oxidative stress induced by the dialysis membrane (an indicator of the biocompatibility of the dialysis membrane). The main clinical consequences of oxidative stress include: atherosclerosis, erythropoietin resistance, malnutrition and amyloidosis associated with hemodialysis. The evaluation of oxidative stress in patients undergoing hemodialysis is performed by measuring the concentration of lipid peroxidation products (malonyldialdehyde, 4-hydroxynonenal, TBARS, F2-isoprostane, oxLDL), protein oxidation (AOPP), protein gelling (AGE), and oxidation of nucleic acids (8-OHdG). The antioxidant treatment strategy consists of replenishing vitamin C, vitamin E, selenium, N-acetylcysteine and coenzyme Q10. On-line hemodialysis, a biocompatible vitamin Ecoated dialysis membrane, an ultra-pure solution for hemodialysis, prevent oxidative stress, reduce the rate of cardiovascular morbidity and mortality and improve life quality of patients treated with regular hemodialysis.
Imbalance of Oxidants and Antioxidants in Haemodialysis Patients
Blood Purification, 1999
Dialysis-related pathology (DRP) observed in long-term haemodialysis patients is increasingly reported. Among DRP manifestations, cardiovascular disease is the most frequent, being the first cause of mortality in haemodialysis patients. Alterations in lipid metabolism and oxidative stress are recognised as major risk factors that could be prevented or reduced by optimal therapy.
Effect of hemodialysis on the antioxidative properties of serum
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2003
In patients with chronic renal failure undergoing regular hemodialysis (HD), oxidative stress is involved in the development of dialysisrelated pathologies. The aim of the study was to measure the effect of HD treatment on the general antioxidative status of serum with special consideration of the specific oxidizability of lipids and proteins. Indicators for the oxidative/antioxidative status of plasma were monitored at the beginning and at the end of a dialysis session on the arterial and venous side of the dialyzer. A decrease in the antioxidant status was accompanied by an increased oxidizability of proteins as well as lipids during HD treatment. During the first passage of the dialyzer, the lag time of lipid oxidation decreased from 114.0 F 19.8 to 81.5 F 18.9 min, the lag time of protein oxidation decreased from 105.0 F 24.6 to 72.9 F 21.3 min and the total antioxidative status decreased from 518 F 24 to 252 F 124 AM trolox equivalents. The carbonyl content of serum proteins was high in patients with end stage renal disease (ESRD) (3.9 F 1.1 vs. 0.9 F 0.1 nmol/mg in controls) but did not change significantly during dialysis procedure. Our data demonstrate that the susceptibility of serum lipids and proteins to oxidative modification is severely increased by HD treatment.
Vitamins (A, C and E) and oxidative status of hemodialysis patients treated with HFR and HFR-Supra
BMC Nephrology, 2016
Background: Hemodiafiltration with on-line endogenous reinfusion (HFR) is an extracorporeal dialytic method that combines diffusion, convection and adsorption. HFR-Supra (HFR-S) is a second-generation system with increased convective permeability and adsorption capability. Previous studies suggested that HFR reduces oxidative stress compared to standard haemodialysis. The principal aim of the present study was to compare antioxidant vitamins behavior and oxidative status of hemodialysis patients treated with HFR and HFR-S. Methods: The study was designed as a multicenter, randomized, crossover trial. Forty-one patients were recruited from 19 dialysis centers and after a 4-month washout stabilization period in on-line hemodiafiltration (ol-HDF), each patient was randomized to a sequence of treatments (HFR-S followed by HFR or viceversa) with each treatment applied over 6 months. Plasma levels of Advanced Oxidation Protein Products, Total Antioxidant Status, vitamins C, A and E and their ligands (Retinol Binding Protein and total lipids) were measured at baseline and at the end of each treatment period. Results: Results show that the higher convective permeability of HFR-S with respect to HFR did not produce additional beneficial effects on the patients' oxidative status, a slight decrease of both Vitamin A and Retinol Binding Protein being the only difference registered in the long-term. However, as compared to ol-HDF, both the re-infusive techniques allowed to reduce the intradialytic loss of Vitamin C and, in the long-term, improve the patients' oxidative status and increase Retinol Binding Protein plasma values. No significant differences were found between the Vitamin C concentration of pre-and post cartridge UF neither in HFR-S nor in HFR showing that the sorbent resin does not adsorb Vitamin C. Conclusion: HFR-S and HFR are almost equivalent in term of impact on antioxidant vitamins and oxidative status of hemodialysis patients. Nonetheless, as compared to ol-HDF, both treatments produced a sensible sparing of Vitamin C and may represent a new approach for reducing oxidative stress and related complications in dialysis patients. Longterm effects of re-infusive treatments on patients' cardiovascular morbidity and mortality need to be evaluated. Trial registration: ClinicalTrials.gov Identifier NCT01492491, retrospectively registered in 10 December 2011.
Lipoperoxidation and hemodialysis
Metabolism, 2008
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 randomized 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 b .01), LDL cholesterol (94.1 ± 39.6 to 76.1 ± 26.6 mg/dL LDL, P b .03), and phospholipids levels (196.5 ± 36.7 to 182.9 ± 36.1 mg/dL, P b .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 b .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 b .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.
Antioxidant Therapy in Hemodialysis Patients
Antioxidants have been used as therapies to decrease oxidative stress and improve CVD risk in hemodialysis (HD) patients. A systematic search of the Medline database (search date 30 April 2011) found 56 studies investigating the effects of antioxidant therapies on biomarkers of oxidative stress (53 studies) or clinical outcomes (3 studies). The majority were small trials using a nonrandomized open-label design with a single HD group (no HD controls). Alpha-tocopherol was the most investigated antioxidant, with 20/25 studies reporting that this vitamin decreased oxidative stress, and one clinical outcome trial in 196 patients finding that it protected against secondary CVD. Studies using vitamin C were more equivocal, with 4/11 showing decreased oxidative stress and one clinical outcome trial showing no effect on morbidity or mortality. N-acetylcysteine was the most efficacious agent, with 4/4 studies indicating a decrease in oxidative stress and one trial (n ¼ 134) showing reduced CVD events. Seven studies have used therapy containing a combination of antioxidants, with five of these reporting decreased oxidative stress. Most intervention studies in HD patients, such as statin therapy and increased dialysis dose, have failed to show improvement in CVD outcomes. Two intervention trials using different antioxidants have found CVD benefits, suggesting that this line of therapy is effective in this resistant population. These studies require validation in larger, adequately powered trials.
Antioxidant status in patients on maintenance hemodialysis
Maintenance haemodialysis (HD) is the mainstay of treatment for the patients with end stage renal disease not suitable for or awaiting renal transplantation. Cardiovascular morbidity is an important complication in these patients. As oxygen free radicals are known to be involved in cardiovascular disease and atherosclerosis, it is possible that the same mechanism of oxidant stress may be involved in this process. This study was planned as there are conflicting reports on the antioxidant status in these patients. 26 patients, with end stage renal disease, who were on maintenance haemodialysis and 24 age matched healthy controls were recruited for the study. There was an increase in plasma and RBC lipid peroxides and serum creatinine and ferritin levels. An increase in plasma superoxide dismutase (SOD) and decrease in plasma Glutathione peroxidase (GP) were observed. There were no significant changes in plasma vitamins A & E levels and in antioxidant enzyme status in erythrocytes. The results of our study point towards the generation of reactive oxygen species in patients on haemodialysis which are not effectively countered by antioxidant defense mechanisms.
Free Radical Biology and Medicine, 2002
The high cardiovascular mortality in patients receiving hemodialysis (HD) has been attributed, in part, to oxidative stress. Here we examined the effectiveness of antioxidants introduced by means of a novel hemolipodialysis (HLD) procedure in terms of reducing oxidative stress during ex vivo blood circulation. Oxidative stress was studied in a model HD system resembling the extracorporeal circulation of blood during clinical HD. Blood circulation produced an increase of up to 280% in free hemoglobin levels and an increase of 320% in electronegative LDL (LDL Ϫ ) subfraction. A significant correlation between LDL Ϫ and free hemoglobin levels confirmed previous findings that LDL Ϫ formation during ex vivo circulation of blood can be mediated by the oxidative activity of free hemoglobin. These effects were significantly attenuated during HLD using a dialysis circuit containing vitamin E with or without vitamin C. By contrast, HLD with vitamin C alone had a marked pro-oxidant effect. TBARS, lipid hydroperoxides, vitamin E and -carotene content in LDL were not significantly altered by the HD procedure. These findings demonstrate the occurrence of oxidative stress in human plasma where lipoproteins are a target and indicate antioxidant-HLD treatment as a specific new approach to decreasing the adverse oxidative stress frequently associated with cardiovascular complications in high-risk populations of uremic patients.