Antioxidant therapy in hemodialysis patients: a systematic review
2011; Elsevier BV; Volume: 81; Issue: 3 Linguagem: Inglês
10.1038/ki.2011.341
ISSN1523-1755
AutoresJeff S. Coombes, Robert G. Fassett,
Tópico(s)Antioxidant Activity and Oxidative Stress
ResumoAntioxidants 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=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. 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=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. Cardiovascular disease (CVD) is the cause of death in ∼34% of hemodialysis (HD) patients.1.McDonald S. Excell L. Livingston B. ANZDATA Registry 2010 Report. 2010http://www.anzdata.org.au/anzdata/AnzdataReport/33rdReport/Ch03.pdfGoogle Scholar Indeed, at all ages, these individuals have a 10- to 20-fold increased risk of death from CVD.2.Raine A.E. Margreiter R. Brunner F.P. et al.Report on management of renal failure in Europe, XXII, 1991.Nephrol Dial Transplant. 1992; 7: 7-35PubMed Google Scholar Clinical trials using a range of interventions aimed at improving CVD outcomes in HD patients have been unsuccessful. These include the use of lipid-lowering therapy in the AURORA trial3.Fellstrom B.C. Jardine A.G. Schmieder R.E. et al.Rosuvastatin and cardiovascular events in patients undergoing hemodialysis.N Engl J Med. 2009; 360: 1395-1407Crossref PubMed Scopus (1596) Google Scholar and 4D trial,4.Wanner C. Krane V. Marz W. et al.Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis.N Engl J Med. 2005; 353: 238-248Crossref PubMed Scopus (2206) Google Scholar increased dialysis dose in the HEMO trial,5.Eknoyan G. Beck G.J. Cheung A.K. et al.Effect of dialysis dose and membrane flux in maintenance hemodialysis.N Engl J Med. 2002; 347: 2010-2019Crossref PubMed Scopus (1576) Google Scholar and the timing of dialysis initiation in the IDEAL trial.6.Cooper B.A. Branley P. Bulfone L. et al.A randomized, controlled trial of early versus late initiation of dialysis.N Engl J Med. 2010; 363: 609-619Crossref PubMed Scopus (655) Google Scholar The only two intervention trials to show a positive effect in this population were those using antioxidant therapy.7.Boaz M. Smetana S. Weinstein T. et al.Secondary prevention with antioxidants of cardiovascular disease in endstage renal disease (SPACE): randomised placebo-controlled trial.Lancet. 2000; 356: 1213-1218Abstract Full Text Full Text PDF PubMed Scopus (934) Google Scholar,8.Tepel M. Van de giet M. Statz M. et al.The antioxidant acetylcysteine reduces cardiovascular events in patients with end-stage renal failure: a controlled trial.Circulation. 2003; 107: 992-995Crossref PubMed Scopus (346) Google Scholar This, combined with evidence that oxidative stress is increased in HD patients and associated with CVD in this population,9.Ikizler T.A. Morrow J.D. Roberts L.J. et al.Plasma F2-isoprostane levels are elevated in chronic hemodialysis patients.Clin Nephrol. 2002; 58: 190-197Crossref PubMed Google Scholar suggests that antioxidant therapy may improve the CVD morbidity and mortality of HD patients. The aims of this review were to systematically appraise the evidence regarding the effects of antioxidant therapy on oxidative stress in HD patients, synthesizing data from biochemical-based studies and a small number of CVD outcome trials. Oxidative stress refers to the situation in which pro-oxidants overwhelm antioxidant defenses, resulting in increased biomarkers of oxidative damage. Pro-oxidants, commonly referred to as reactive species, include reactive oxygen species and reactive nitrogen species, of which the most common reactive nitrogen species is nitric oxide. The reactive oxygen species consist of free radicals, molecules lacking a paired electron in their outer orbital such as the superoxide anion and hydroxyl radical, and other oxygen-derived molecules such as hydrogen peroxide and hypochlorous acid.10.Halliwell B. Reactive oxygen species in living systems: source, biochemistry, and role in human disease.Am J Med. 1991; 91: 14S-22SAbstract Full Text PDF PubMed Scopus (825) Google Scholar Reactive species have a complex role in health and disease, highlighted by providing the stimulus to relax blood vessels.11.Llorens S. Nava E. Cardiovascular diseases and the nitric oxide pathway.Curr Vasc Pharmacol. 2003; 1: 335-346Crossref PubMed Scopus (35) Google Scholar When antioxidant capacity is overwhelmed, numerous compounds such as lipids, proteins, carbohydrates, and DNA become susceptible to oxidative damage. Oxidation of circulating lipids, such as low-density lipoproteins (LDLs), is implicated in the pathogenesis of vascular disease through the formation of atherosclerotic plaque.12.Stocker R. Keaney Jr., J.F. Role of oxidative modifications in atherosclerosis.Physiol Rev. 2004; 84: 1381-1478Crossref PubMed Scopus (2105) Google Scholar The body's antioxidant defenses are endogenous and exogenous (dietary and therapeutic). Dietary antioxidants include vitamin E, vitamin C (ascorbic acid), and β-carotene. Vitamin E refers to eight structurally similar compounds, α-, β-, γ-, and δ-tocopherol, and α-, β-, γ-, and δ-tocotrienol. The α-tocopherol has the highest biological activity and is therefore often referred to as vitamin E. The α-tocopherol and β-carotene are lipid-soluble molecules, whereas vitamin C resides in the aqueous phase. Importantly, many antioxidants exhibit synergistic relationships with other antioxidants; for example, vitamin C is capable of recycling α-tocopherol. Therapeutic antioxidants include compounds such as N-acetylcysteine and bardoxolone.13.Pergola P.E. Krauth M. Huff J.W. et al.Effect of bardoxolone methyl on kidney function in patients with T2D and Stage 3b-4 CKD.Am J Nephrol. 2011; 33: 469-476Crossref PubMed Scopus (201) Google Scholar Evidence for the beneficial effects of antioxidants on CVD is found in observational studies such as the World Health Organization's MONICA (MONitoring trends and determinants In CArdiovascular disease) Study,14.Gey K.F. Moser U.K. Jordan P. et al.Increased risk of cardiovascular disease at suboptimal plasma concentrations of essential antioxidants: an epidemiological update with special attention to carotene and vitamin C.Am J Clin Nutr. 1993; 57: 787S-797SPubMed Google Scholar the Nurses Health Study,15.Colditz G.A. Willett W.C. Hunter D.J. et al.Family history, age, and risk of breast cancer. Prospective data from the Nurses' Health Study.JAMA. 1993; 270: 338-343Crossref PubMed Google Scholar the US Physicians study,16.Rimm E.B. Stampfer M.J. Ascherio A. et al.Vitamin E consumption and the risk of coronary heart disease in men.N Engl J Med. 1993; 328: 1450-1456Crossref PubMed Scopus (2137) Google Scholar and randomized controlled clinical trials such as CHAOS (Cambridge Heart AntiOxidant Study).17.Stephens N.G. Parsons A. Schofield P.M. et al.Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS).Lancet. 1996; 347: 781-786Abstract PubMed Scopus (1671) Google Scholar However, large trials including the HOPE (Heart Outcomes Prevention Evaluation) trial18.Yusuf S. Dagenais G. Pogue J. et al.Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators [see comments].N Engl J Med. 2000; 342: 154-160Crossref PubMed Scopus (1763) Google Scholar and the Heart Protection Study19.Heart Protection Study Collaborative Group MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20,536 high-risk individuals: a randomised placebo-controlled trial.Lancet. 2002; 360: 23-33Abstract Full Text Full Text PDF PubMed Scopus (1367) Google Scholar have not supported the notion that antioxidants provide CVD protection. Proponents of antioxidants speculate that these therapies would be most beneficial in individuals with chronically elevated oxidative stress rather than the general population.20.Himmelfarb J. Stenvinkel P. Ikizler T.A. et al.The elephant in uremia: oxidant stress as a unifying concept of cardiovascular disease in uremia.Kidney Int. 2002; 62: 1524-1538Abstract Full Text Full Text PDF PubMed Scopus (1008) Google Scholar HD patients have elevated oxidative stress compared with healthy matched controls, and this is postulated as contributing to the high levels of CVD morbidity and mortality in these individuals.9.Ikizler T.A. Morrow J.D. Roberts L.J. et al.Plasma F2-isoprostane levels are elevated in chronic hemodialysis patients.Clin Nephrol. 2002; 58: 190-197Crossref PubMed Google Scholar Indeed, numerous studies, included in this review, have compared oxidative stress between HD patients and controls. The markers of oxidative stress shown to be elevated include F2-isoprostanes,21.Handelman G.J. Walter M.F. Adhikarla R. et al.Elevated plasma F2-isoprostanes in patients on long-term hemodialysis.Kidney Int. 2001; 59: 1960-1966Abstract Full Text Full Text PDF PubMed Scopus (204) Google Scholar lipid hydroperoxides,22.Chao J.C. Yuan M.D. Chen P.Y. et al.Vitamin C and E supplements improve the impaired antioxidant status and decrease plasma lipid peroxides in hemodialysis patients small star, filled.J Nutr Biochem. 2002; 13: 653-663Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar oxidized anti-LDL antibodies,23.Bayes B. Pastor M.C. Bonal J. et al.Homocysteine and lipid peroxidation in haemodialysis: role of folinic acid and vitamin E.Nephrol Dial Transplant. 2001; 16: 2172-2175Crossref PubMed Google Scholar the oxidizability of LDL,24.Ohkawa S. Yoneyama T. Shimoi K. et al.Pro-oxidative effect of alpha-tocopherol in the oxidation of LDL isolated from co-antioxidant-depleted non-diabetic hemodialysis patients.Atherosclerosis. 2004; 176: 411-418Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar free sulfhydryl groups,25.Himmelfarb J. McMonagle E. McMenamin E. Plasma protein thiol oxidation and carbonyl formation in chronic renal failure.Kidney Int. 2000; 58: 2571-2578Abstract Full Text Full Text PDF PubMed Scopus (227) Google Scholar carbonyl groups,26.Odetti P. Garibaldi S. Gurreri G. et al.Protein oxidation in hemodialysis and kidney transplantation.Metabolism. 1996; 45: 1319-1322Abstract Full Text PDF PubMed Scopus (63) Google Scholar 3-chlorotyrosine,27.Himmelfarb J. McMenamin M.E. Loseto G. et al.Myeloperoxidase-catalyzed 3-chlorotyrosine formation in dialysis patients.Free Radic Biol Med. 2001; 31: 1163-1169Crossref PubMed Scopus (105) Google Scholar and advanced oxidation protein products.28.Witko-Sarsat V. Friedlander M. Capeillere-Blandin C. et al.Advanced oxidation protein products as a novel marker of oxidative stress in uremia.Kidney Int. 1996; 49: 1304-1313Abstract Full Text PDF PubMed Scopus (1633) Google Scholar Figure 1 shows that oxidative stress may be increased because of a loss of antioxidants during dialysis,29.Ha T.K. Sattar N. Talwar D. et al.Abnormal antioxidant vitamin and carotenoid status in chronic renal failure.QJM. 1996; 89: 765-769Crossref PubMed Scopus (67) Google Scholar interactions between blood and dialysis membrane,30.Cheung A.K. Biocompatibility of hemodialysis membranes.J Am Soc Nephrol. 1990; 1: 150-161PubMed Google Scholar bacterial products in dialysate crossing the dialysis membrane directly or indirectly stimulating release of reactive species by neutrophils, and malnutrition decreasing the uptake of dietary antioxidants.31.Hu M.L. Louie S. Cross C.E. et al.Antioxidant protection against hypochlorous acid in human plasma.J Lab Clin Med. 1993; 121: 257-262PubMed Google Scholar On the basis of the evidence of elevated oxidative stress in predialysis chronic kidney disease patients, it is evident that the disease itself contributes to this state.32.Oberg B.P. McMenamin E. Lucas F.L. et al.Increased prevalence of oxidant stress and inflammation in patients with moderate to severe chronic kidney disease.Kidney Int. 2004; 65: 1009-1016Abstract Full Text Full Text PDF PubMed Scopus (606) Google Scholar Indeed, a recent study showed that estimated glomerular filtration rate, inflammation, and high-density lipoprotein cholesterol were the main determinants of elevated reactive species production in nondialysed CKD patients.33.Morena M. Patrier L. Jaussent I. et al.Reduced glomerular filtration rate, inflammation and HDL cholesterol as main determinants of superoxide production in non-dialysis chronic kidney disease patients.Free Rad Res. 2011; 45: 735-745Crossref PubMed Scopus (6) Google Scholar In addition, HD activates immune cells and increases production of reactive oxygen species, leading to an acute inflammatory response and oxidative stress. Both processes are involved in the pathogenesis of atherosclerotic CVD.34.Steinberg D. Antioxidants in the prevention of human atherosclerosis. Summary of the proceedings of a National Heart, Lung, and Blood Institute Workshop: September 5-6, 1991, Bethesda, Maryland.Circulation. 1992; 85: 2337-2344Crossref PubMed Google Scholar Therefore, therapies that reduce production of these damaging molecules or decrease their ability to cause damage may improve the CVD morbidity and mortality of HD patients. Plasma levels of vitamin E are decreased during HD, suggesting that vitamin E therapy may improve biomarkers of oxidative stress in this patient population.35.Hodkova M. Dusilova-Sulkova S. Kalousova M. et al.Influence of oral vitamin E therapy on micro-inflammation and cardiovascular disease markers in chronic hemodialysis patients.Ren Fail. 2006; 28: 395-399Crossref PubMed Scopus (27) Google Scholar,36.Giray B. Kan E. Bali M. et al.The effect of vitamin E supplementation on antioxidant enzyme activities and lipid peroxidation levels in hemodialysis patients.Clin Chim Acta. 2003; 338: 91-98Crossref PubMed Scopus (40) Google Scholar A comprehensive literature search was completed on 30 April 2011 using the Medline database (PubMed) with the following MESH headings and search terms: dialysis AND antioxidants OR vitamin E OR tocopherol OR vitamin C OR ascorbic acid OR selenium OR acetylcysteine OR vitamin A OR beta-carotene OR coenzyme Q10; the limits included the following: humans and clinical trials. Only the studies that investigated the effects of oral antioxidant therapy on a marker/s of oxidative stress or a CVD outcome measure in patients undergoing HD were included. Studies using vitamin-E-coated dialyzer membranes or those that only looked at changes in plasma antioxidant levels were not included. Owing to the large variety of oxidative stress outcome measures, a meta-analytical approach was not possible. Antioxidants were considered to have had a positive effect if administration was associated with a significant decrease of a biomarker or biomarkers of oxidative stress. Of the 298 articles identified, 56 original investigation articles met the criteria for inclusion in this review. Of these, 53 assessed the effects of antioxidant therapy on a biomarker or biomarkers of oxidative stress (Tables 1, 2, 3 and 4), whereas additional 3 studies investigated the effects of antioxidants on CVD end points (Table 5). Summary tables have been divided into those using α-tocopherol (Table 1, 25 studies), vitamin C (Table 2, n=11), and others (Table 3).Table 1Studies investigating the effects of α-tocopherol therapy on oxidative stress and antioxidants in HD patientsStudyDesignGroups (n)Dose (oral unless otherwise stated)Therapy durationEffects of therapy on outcome measuresOxidative stressAntioxidantsGiardini et al.†38.Giardini O. Taccone-Gallucci M. Lubrano R. et al.Effects of alpha-tocopherol administration on red blood cell membrane lipid peroxidation in hemodialysis patients.Clin Neph. 1984; 21: 174-177PubMed Google ScholarOpen label with untreated healthy controls1. HD patients given α-tocopherol acetate (19)2. Healthy controls untreated (19)300mg/day (IM)15 daysComparing predialysis data Decreased erythrocyte MDAComparing predialysis data Increased erythrocyte α-tocopherolLubrano et al.†39.Lubrano R. Taccone-Gallucci M. Mazzarella V. et al.Relationship between red blood cell lipid peroxidation, plasma hemoglobin, and red blood cell osmotic resistance before and after vitamin E supplementation in hemodialysis patients.Artif Organs. 1986; 10: 245-250Crossref PubMed Scopus (23) Google ScholarOpen label with untreated healthy controls1. HD patients given α-tocopherol acetate (9)2. Healthy controls untreated (9)300mg/day (IM)15 daysComparing predialysis data Decreased erythrocyte MDAComparing predialysis data Increased erythrocyte α-tocopherolTaccone-Gallucci et al.†40.Taccone-Gallucci M. Giardini O. Ausiello C. et al.Vitamin E supplementation in hemodialysis patients: effects on peripheral blood mononuclear cells lipid peroxidation and immune response.Clin Nephrol. 1986; 25: 81-86PubMed Google ScholarOpen label with untreated healthy controls1. HD patients given α-tocopherol acetate (10)2. Healthy controls untreated (10)300mg/day (IM)15 daysComparing predialysis data Decreased PBMC MDAComparing predialysis data No effect on PBMC α-tocopherolTaccone-Gallucci et al.†41.Taccone-Gallucci M. Lubrano R. Del Principe D. et al.Platelet lipid peroxidation in haemodialysis patients: effects of vitamin E supplementation.Nephrol Dial Transplant. 1989; 4: 975-978PubMed Google ScholarOpen label with untreated healthy controls1. HD patients given α-tocopherol acetate (10)2. Healthy controls untreated (10)300mg/day (IM)15 daysComparing predialysis data Decreased platelet MDAComparing predialysis data Increased platelet α-tocopherol (similar value to control group at the end of treatment)Lubrano et al.†43.Lubrano R. Taccone-Gallucci M. Piazza A. et al.Vitamin E supplementation and oxidative status of peripheral blood mononuclear cells and lymphocyte subsets in hemodialysis patients.Nutrition. 1992; 8: 94-97PubMed Google ScholarOpen label with untreated healthy controls1. HD patients given α-tocopherol acetate (10)2. Healthy controls untreated (10)300mg/day (IM)15 daysComparing predialysis data Decreased PBMC MDAYukawa et al.#42.Yukawa S. Sonobe M. Tone Y. et al.Prevention of aortic calcification in patients on hemodialysis by long-term administration of vitamin E.J Nutr Sci Vitaminol (Tokyo). 1992Crossref Scopus (12) Google ScholarOpen label with untreated HD controls1. HD patients given α-tocopherol (17)2. HD patients untreated (17)200–600mg/day4 yearsSampling times not provided Decreased MDAPanzetta et al.44.Panzetta O. Cominacini L. Garbin U. et al.Increased susceptibility of LDL to in vitro oxidation in patients on maintenance hemodialysis: effects of fish oil and vitamin E administration.Clin Nephrol. 1995; 44: 303-309PubMed Google ScholarOpen label, crossover (crossing between fish oil+α-tocopherol and tocopherol only)1. HD patients given fish oil+α-tocopherol (14)2. Same HD patients given α-tocopherol only (14)1. α-tocopherol 20IU/day2. α-tocopherol 50IU/day1. 30 days2. 30 daysSampling times not provided Increased LDL oxidation lag phase on both treatmentsSampling times not provided Increased LDL α-tocopherol on both treatmentsSanaka et al.45.Sanaka T. Takahashi C. Sanaka M. et al.Accumulation of phosphatidylcholine-hydrogen peroxide in dialysis patients with diabetic nephropathy.Clin Nephrol. 1995; 44: 533-537Google ScholarOpen label with untreated HD controls1. HD patients with NIDDM given α-tocopherol+probucol (9)2. HD patients with NIDDM untreated (13)600mg/day α-tocopherol+500mg/day probucol12 monthsComparing changes from pre- to post-dialysis No significant differences between groups in plasma PCOOH levelsYukawa et al.#46.Yukawa S. Hibino A. Maeda T. et al.Effect of alpha-tocopherol on in vitro and in vivo metabolism of low-density lipoproteins in haemodialysis patients.Nephrol Dial Transplant. 1995; 10: 1-3Crossref PubMed Scopus (37) Google ScholarOpen label with treated healthy controls1. HD patients given α-tocopherol (5)2. Healthy controls given α-tocopherol (5)600mg/day2 weeksComparing predialysis data Decreased MDA-LDLSuppressed the degradation rate of LDL in macrophagesImproved disappearance rate of LDL from circulationCristol et al.°47.Cristol J.P. Bosc J.Y. Badiou S. et al.Erythropoietin and oxidative stress in haemodialysis: beneficial effects of vitamin E supplementation.Nephrol Dial Transplant. 1997; 12: 2312-2317Crossref PubMed Scopus (162) Google ScholarOpen label with treated healthy controls1. HD patients given α-tocopherol (7)2. Healthy controls given α-tocopherol (38)500mg/day6 monthsSampling times not provided Decreased serum MDASampling times not provided Increased erythrocyte α-tocopherolNo effect on erythrocyte GSH or erythrocyte SODRoob et al.48.Roob J.M. Khoschsorur G. Tiran A. et al.Vitamin E attenuates oxidative stress induced by intravenous iron in patients on hemodialysis.J Am Soc Nephrol. 2000; 11: 539-549PubMed Google ScholarOpen label, randomized, crossover (crossing between α-tocopherol and untreated)HD patients receiving 100mg of iron hydroxide+RRR-rac-α-tocopherol (22)1200IUOne dose, 6h before dialysis sessionMeasurements taken before, during, and after iron infusion (iron infusion was started 30min after HD session and lasted 20min) Decreased plasma MDA Decreased lipid peroxidesMeasurements taken before, during, and after iron infusion (iron infusion was started 30min after HD session and lasted 20min) Increased plasma α-tocopherol and retinolNo effect on plasma γ-tocopherol, β-carotene, lycopene, or vitamin CNemeth et al.49.Nemeth I. Turi S. Bereczki C. Vitamin E alleviates the oxidative stress of erythropoietin in uremic children on hemodialysis.Pediatr Nephrol. 2000; 14: 13-17Crossref PubMed Scopus (45) Google ScholarOpen label, noncontrolledHD patients (children) receiving rhEPO+α-tocopherol (10)15mg/kg/day2 weeksComparing predialysis data Decreased GSSGComparing predialysis data Increased GSH back to pre-treatment levelIslam et al.*50.Islam K.N. O'Byrne D. Devaraj S. et al.Alpha-tocopherol supplementation decreases the oxidative susceptibility of LDL in renal failure patients on dialysis therapy.Atherosclerosis. 2000; 150: 217-224Abstract Full Text Full Text PDF PubMed Scopus (114) Google ScholarOpen label with treated healthy controls1. HD patients given RRR-α-tocopherol (16)2. PD patients given RRR-α-tocopherol (17)3. Healthy controls given α-tocopherol (17)800IU/day12 weeksComparing predialysis data Decreased LDL oxidative susceptibility in all groups (greater benefits in PD patients)Comparing predialysis data Increased lipid standardized plasma and LDL α-tocopherolO'Byrne et al.*51.O'Byrne D. Devaraj S. Islam K.N. et al.Low-density lipoprotein (LDL)-induced monocyte-endothelial cell adhesion, soluble cell adhesion molecules, and autoantibodies to oxidized-LDL in chronic renal failure patients on dialysis therapy.Metabolism. 2001; 50: 207-215Abstract Full Text PDF PubMed Scopus (47) Google ScholarOpen label with treated healthy controls1. HD patients given RRR-α-tocopherol (16)2. PD patients given RRR-α-tocopherol (17)3. Healthy controls given α-tocopherol (17)800IU/day12 weeksComparing predialysis data No effect on plasma autoantibodies to oxLDLComparing predialysis data Increased LDL α-tocopherolBayes et al.52.Bayes B. Pastor M.C. Bonal J. et al.Homocysteine and lipid peroxidation in haemodialysis: role of folinic acid and vitamin E.Nephrol Dial Transplant. 2001; 16: 2172-2175Crossref PubMed Scopus (56) Google ScholarOpen label with untreated healthy controls1. HD patients given α-tocopherol (16)2. Healthy controls untreated (30)400mg/dialysis session3 monthsComparing predialysis data Decreased plasma MDA Decreased plasma autoantibodies to oxLDLComparing predialysis data Increased plasma α-tocopherolGalli et al.53.Galli F. Varga Z. Balla J. et al.Vitamin E, lipid profile, and peroxidation in hemodialysis patients.Kidney Int Suppl. 2001; 78: S148-S154Crossref PubMed Google ScholarOpen label with untreated healthy controls1. HD patients given α-tocopheryl acetate (19)2. Healthy controls untreated (30)800mg/day3 weeksComparing predialysis data Decreased plasma TBARS Increased plasma nitric oxideComparing predialysis data Increased plasma α-tocopherol Increased plasma GSHGiray et al.54.Giray B. Kan E. Bali M. et al.The effect of vitamin E supplementation on antioxidant enzyme activities and lipid peroxidation levels in hemodialysis patients.Clinica Chimica Acta. 2003; 338: 91-98Crossref PubMed Scopus (59) Google ScholarOpen label with untreated healthy controls1. HD patients given α-tocopherol (36)2. Healthy controls untreated (36)600mg/day14 weeksComparing predialysis data Decreased plasma TBARSComparing predialysis data Increased plasma GPX and SOD activityBadiou et al.°55.Badiou S. Cristol J.P. Morena M. et al.Vitamin E supplementation increases LDL resistance to ex vivo oxidation in hemodialysis patients.Int J Vitam Nutr Res. 2003; 73: 290-296Crossref PubMed Scopus (18) Google ScholarOpen label with treated healthy controls1. HD patients given α-tocopherol (14)2. Healthy controls given α-tocopherol (6)500mg/day6 monthsSampling times not provided Decreased plasma TBARS Copper-induced LDL oxidationSampling times not provided Increased plasma lipoprotein α-tocopherolSmith et al.56.Smith K.S. Lee C.L. Ridlington J.W. et al.Vitamin E supplementation increases circulating vitamin E metabolites tenfold in end-stage renal disease patients.Lipids. 2003; 38: 813-819Crossref PubMed Scopus (50) Google ScholarOpen label, crossover (crossing between untreated and α-tocopherol)HD patients given RRR-α-tocopherol (11)400IU/day2 monthsComparing predialysis data No effect on plasma isoprostanesComparing postdialysis data No effect on plasma isoprostanesComparing changes from pre- to postdialysis No effect on plasma isoprostanesComparing predialysis data Increased plasma α-tocopherolComparing postdialysis data Increased plasma α-tocopherolComparing changes from pre- to postdialysis No effect on plasma α-tocopherolHodkova et al.^57.Hodkova M. Dusilova-Sulkova S. Skalicka A. et al.Influence of parenteral iron therapy and oral vitamin E supplementation on neutrophil respiratory burst in chronic hemodialysis patients.Ren Fail. 2005; 27: 135-141Crossref PubMed Scopus (16) Google ScholarOpen label with untreated healthy controls1. HD patients given α-tocopherol+IV iron (7)2. Healthy controls untreated (14)200mg/day7 daysComparing predialysis data Decreased neutrophil respiratory burst during HD and iron administrationNo effect on plasma AOPPComparing predialysis data Increased serum α-tocopherolDiepeveen et al.58.Diepeveen S.H. Verhoeven G.W. Van Der Palen J. et al.Effects of atorvastatin and vitamin E on lipoproteins and oxidative stress in dialysis patients: a randomised-controlled trial.J Intern Med. 2005; 257: 438-445Crossref PubMed Scopus (67) Google ScholarRandomized, placebo controlled, double blind (factorial design)1. HD patients given atorvastatin+placebo α-tocopherol (13)2. HD patients given α-tocopherol+placebo atorvastatin (10)3. HD patients given atorvastatin+α-tocopherol (11)4. HD patients given placebo atorvastatin+placebo α-tocopherol (10)800IU/day12 weeksComparing predialysis data Decreased in vitro LDL oxidizability No effect on plasma oxLDL levelsComparing predialysis data Increased serum α-tocopherolHodkova et al.^35.Hodkova M. Dusilova-Sulkova S. Kalousova M. et al.Influence of oral vitamin E therapy on micro-inflammation and cardiovascular disease markers i
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