Imbalance of Oxidants and Antioxidants in Haemodialysis Patients (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.
Seminars in Dialysis, 2018
Oxidative stress (OS) is the result of prooxidant molecules overwhelming the antioxidant defense mechanisms. Hemodialysis (HD) constitutes a state of elevated inflammation and OS, due to loss of antioxidants during dialysis and activation of white blood cells triggering production of reactive oxygen species. Dialysis vintage, dialysis methods, and type and condition of vascular access, biocompatibility of dialyzer membrane and dialysate, iron administration, and anemia all can play a role in aggravating OS, which in turn has been associated with increased morbidity and mortality. Oral or intravenous administration of antioxidants may detoxify the oxidative molecules and at least in part repair OS-mediated tissue damage. Lifestyle interventions and optimization of a highly biocompatible HD procedure might ameliorate OS development in dialysis.
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.
Changes in antioxidant status associated with haemodialysis in chronic kidney disease
Ghana Medical Journal
Oxidative stress has been implicated in the pathogenesis, progression of chronic kidney disease (CKD) and development of cardiovascular complications. Hemodialysis (HD) has also been described to contribute significantly to oxidative stress in CKD patients, though reports are conflicting. Objective: We evaluated the effects of one session of HD on the antioxidant capacity and lipid peroxidation in CKD patients. Method: Thirty-six CKD patients requiring HD were recruited into this study. Participants were naïve to HD and each completed a session of three hours using polysulfone membrane dialyzers. Blood samples were collected before and after dialysis. Total antioxidant capacity (TAC) was measured by ferric reducing antioxidant power (FRAP) while malondialdehyde (MDA) was measured using thiobarbituric acid-reactive substance (TBARS). Comparison was made between pre-HD and post-HD values of TAC and MDA respectively, p value of <0.05 was taken as significant. Result: Mean age and estimated glomerular filtration rate of subjects were 45 ±15 years and 6.3± 4.7mls/1.73m 2 respectively. There was significant decrease in the mean TAC from 1232.2 ± 495.6 µmol Trolox equiv/ to 832.4 ± 325.7 µmol Trolox equiv/L post-dialysis (p< 0.001) while MDA values were similar before and after HD (11.8 ± 1.8 vs 11.8 ± 2.331)µmol/L (p> 0.05). There was no significant association between changes in antioxidant status following HD with blood flow rate, ultrafiltration volume nor dialyzer per size. Conclusion: A session of HD in patients with CKD is associated with significant reduction of the total antioxidants capacity; and no effect on MDA levels.
Blood Purification, 2000
Oxidative stress which results from an imbalance between reactive oxygen species production and antioxidant defense mechanisms is now well recognized in hemodialysis (HD) patients and could be involved in dialysis-related pathologies such as accelerated atherosclerosis, amyloidosis and anemia. In order to evaluate the rationale for preventive intervention against oxidative damage during HD, we review the factors that are implied and may be responsible for the imbalance between pro- and antioxidative mechanisms. The inflammatory state mainly due to hemobioincompatibility of the dialysis system plays a critical role in the production of free oxygen radical species contributing by this way to worsen the prooxidant status of uremic patients. Two factors largely contribute to the stimulation of the NADPH oxidase: hemoreactivity of the membrane and trace amounts of endotoxins. The antioxidant system is severely impaired in uremic patients and gradually altered with the degree of renal failure. HD could further impair this antioxidant system mainly by losses of (a) hydrophilic unbound small-molecular-weight substances such as vitamin C, (b) trace elements and (c) enzyme-regulatory compounds. Two main axes may be proposed in order to prevent and/or to decrease oxidative stress in HD patients. One consists in improving the hemocompatibility of the dialysis system mainly by using a dialyzer with low hemoreactivity and ultrapure, sterile, nonpyrogenic dialysate. The other consists in supplementing the deficiency patients with antioxidants. This could be achieved by oral or perdialytic supplementation. Vitamin E could be bound on dialyzer membrane. Alternatively, hemolipodialysis consists in loading HD patients with vitamin C or E via an ancillary circuit made of vitamin E-rich liposomes. The presence of liposomes could also facilitate the removal of hydrophobic prooxidative substances.
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.
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.
Oxidative stress in hemodialysis patients: Is NADPH oxidase complex the culprit?
Kidney International, 2002
Oxidative stress results from an imbalance between oxidant production, including reactive oxygen species (ROS), reactive nitrogen species (RNS), chlorinated compounds, and antioxidant defense mechanisms. Most reports prove that oxidative stress is present in ESRD patients. Several studies tend to accreditate the hypothesis by which oxidative stress is a strong co-factor for the development of complications related to long-term HD such as atherosclerosis, amyloidosis, malnutrition, anemia, and infection. In order to evaluate the rationale for curative action against oxidative damage in chronic renal failure patients, we reviewed the putative factors involved in this process. Antioxidant systems are severely impaired in uremic patients and gradually altered with the degree of renal failure. Moreover, the inflammatory state caused by the hemoincompatibility of the dialysis system plays a critical role in the activation of NADPH oxidase, aggravating the pro-oxidant status of uremic patients. Prevention of ROS overproduction by improvement of dialysis biocompatibility, an important component of adequate dialysis, might be completed by antioxidant supplementation.