Antioxidant therapy in hemodialysis patients: a systematic review

Abstract

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.

Ankyrin is the major oxidised protein in erythrocyte membranes from end-stage renal disease patients on chronic haemodialysis and oxidation is decreased by dialysis and vitamin C supplementation

“…Despite evidence for harmful effects in the general population of high doses of some common supplements (β-carotene, vitamin E, vitamin A) [50,51], there is evidence, although limited, that chronically haemodialysed patients could benefit from the use of antioxidants to prevent cardiovascular complications [52,53]. However, there are also some contradictory findings which suggest that the mechanism and consequences of oxidative damage in ESRD need closer examination before antioxidant interventions are evaluated [54].…”

Oxidative Dna Damage and Mortality in Hemodialysis and Peritoneal Dialysis Patients

“…Relatively few studies have documented mortality prediction by oxidative stress in dialysis patients (14)(15)(16)(17) and antioxidant therapy in dialysis patients to reduce CVD has in general been unsuccessful (40); however, two studies reported a positive effect of interventions targeting oxidative stress (41,42).…”

Provision of Antioxidant Therapy in Hemodialysis (PATH)

“…These data highlight the uncertainties surrounding the use of antioxidants in patients receiving dialysis. Although .50 studies investigating antioxidants in patients undergoing hemodialysis have been published, there is no consensus on procedures for optimal study design, and no previous studies have measured both appropriate biomarkers and clinical outcomes in sufficiently large populations to draw meaningful conclusions (reviewed in Coombes and Fassett 39 ). Further studies, probably using different antioxidants and perhaps assessing different endpoints, are warranted to fully test whether antioxidants may confer benefit to this patient population.…”

“…This has led to the suggestion that oxidative stress pathways are a "nontraditional" cardiovascular risk factor for patients receiving dialysis therapy and that antioxidant therapies may be more effective in this population than in studies of primary and secondary risk prevention in the absence of advanced kidney disease. 39 We chose to study a combination of mixed tocopherols and ALA as antioxidant therapy for several reasons. First, in two separate pilot studies, the separate provision of a-tocopherol and the thiol-containing antioxidant N-acetyl cysteine had some benefit in reducing cardiovascular events rates in patients receiving MHD.…”