Low Plasma α-Tocopherol Concentrations and Adverse Clinical Outcomes in Diabetic Hemodialysis Patients

Abstract

SummaryBackground and objectives Trials with the antioxidant vitamin E have failed to show benefit in the general population. Considering the different causes of death in ESRD, this study investigated the association between plasma concentrations of a-tocopherol and specific clinical outcomes in diabetic hemodialysis patients.Design, settings, participants, & measurements In 1046 diabetic hemodialysis patients (participants of the German Diabetes and Dialysis Study), a-tocopherol was measured in plasma by reversed-phase HPLC. By Cox regression analyses, hazard ratios were determined for prespecified end points according to baseline plasma a-tocopherol levels: sudden death (n=134), myocardial infarction (n=172), stroke (n=89), combined cardiovascular events (n=398), fatal infection (n=107), and all-cause mortality (n=508).Results Patients had a mean age of 6668 years, and mean plasma a-tocopherol level was 22.869.6 mmol/L. Levels of a-tocopherol were highly correlated to triglycerides (r=0.63, P,0.001). Patients in the lowest a-tocopherol quartile had (in unadjusted analyses) a 79% higher risk of stroke and a 31% higher risk of all-cause mortality compared with patients in the highest quartile. The associations were attenuated after adjustment for confounders (hazard ratio stroke =1.56, 95% confidence interval=0.75-3.25; hazard ratio mortality =1.22, 95% confidence interval=0.89-1.69, respectively). There was no association between a-tocopherol and myocardial infarction, sudden death, or infectious death.Conclusions Plasma a-tocopherol concentrations were not independently associated with cardiovascular outcomes, infectious deaths, or all-cause mortality in diabetic hemodialysis patients. The lack of association can partly be explained by a confounding influence of malnutrition, which should be considered in the planning of trials to reduce cardiovascular risk in dialysis patients.

Plasma Retinol Concentration Is Mainly Driven by Transthyretin in Hemodialysis Patients

“…Regarding vitamin E, our findings are very similar to what has been reported in literature [7]: plasma concentration of tocopherol and tocopherol/TG are correlated with poor outcomes, but this effect does not resist to adjustment with other parameters and thus, plasma tocopherol concentration is only a surrogate marker of the measured outcome, i.e. death.…”

“…However, pathophysiological explanations for the patients' benefit of survival in case of high concentrations of plasma retinol are not clear. In another study, high tocopherol levels were associated with a better survival, but this effect disappeared with adjustment with other parameters [7]. To our best knowledge, no …”

Dietary supplement use among patients with chronic kidney disease

“…Data from the literature also demonstrates more specific indications for DS in this patient population, as for instance fish oil supplementation and aspirin for arteriovenous fistula protection in patients requiring hemodialysis (Irish et al, 2017) or alpha-tocopherol for prevention of cardio-vascular mortality in the highly burdened diabetic hemodialysis cohort (Espe et al, 2013). Similarly to the results in the general population, these DS have not been found to be associated with clinical benefit in most studies (Espe et al, 2013;Irish et al, 2017), although there are reports on improvement in lipid profile, oxidative stress, pruritus or erythropoietin demand in CKD patients following intake of omega-3 polyunsaturated fatty acids (Vergili-Nelsen, 2003;Bouzidi et al, 2010). However, patients with CKD constitute a different population than people with no kidney disease.…”

Provision of Antioxidant Therapy in Hemodialysis (PATH)

“…[1][2][3][4][5][6][7][8][9][10][11] Elevated biomarkers of the inflammatory response-serum high-sensitivity C-reactive protein (hsCRP) and serum IL-6 concentrations, which are also highly prevalent in this population-are robust predictors of cardiovascular events and mortality and have been linked to increased oxidative stress. [12][13][14][15][16][17][18] Further, the systemic inflammatory response and increased oxidative stress are associated with poor response to erythropoietinstimulating agent (ESA) therapy.…”