Elsevier

Metabolism

Volume 57, Issue 10, October 2008, Pages 1369-1374
Metabolism

Lipoperoxidation and hemodialysis

https://doi.org/10.1016/j.metabol.2008.05.004Get rights and content

Abstract

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 < .01), LDL cholesterol (94.1 ± 39.6 to 76.1 ± 26.6 mg/dL LDL, P < .03), and phospholipids levels (196.5 ± 36.7 to 182.9 ± 36.1 mg/dL, P < .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 < .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 < .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.

Introduction

Oxidative stress defines an imbalance between the formation of reactive oxygen species and antioxidative defense mechanisms. There is mounting evidence indicating that uremia in general is associated with enhanced oxidative stress and a high incidence of premature atherosclerosis [1]. Uremia-associated dyslipidemia, hypertension, and the cause of renal disease, for example, diabetes, have also been implicated as underlying mechanisms. The relative risk of death from myocardial infarction has been reported to be at least 5 times greater in patients receiving some form of renal replacement therapy than in the general population [2]. It has been suggested that renal replacement therapy in uremic patients on hemodialysis or peritoneal dialysis may contribute to oxidative stress and reduce antioxidant levels in these patients [3], [4], [5]. Loss or deficiency of antioxidant activity (eg, vitamin E deficiency) may also contribute to enhanced oxidative stress in uremia. Boaz et al [6] reported reduced cardiovascular end points and myocardial infarction in hemodialysis patients with prevalent cardiovascular disease supplemented with 800 IU/d vitamin E. In hemodialysis patients, reduced plasma total vitamin C concentration has been demonstrated [4], [7]. This deficiency is probably due to a dietary restriction of fresh fruit and vegetables to avoid hyperkalemia, and the loss of the vitamin during dialysis sessions [7], [8], [9], [10]. Some authors have identified vitamin C as a predictor of cardiovascular event rate in dialysis patients[11]. However, the results of studies on the use of antioxidant supplements are inconsistent. Schulz et al [11] failed to detect any acute reduction in lipoprotein antioxidative defense by activated cells during hemodialysis in a study of 12 patients. These authors did not find a link between cuprophane membranes and a mechanism that might contribute to accelerated atherosclerosis in hemodialysis. However, the significance of enhanced oxidative stress in renal patients has been further elucidated in clinical end point studies. Unfortunately, only a few antioxidant intervention studies with clinical end points have been published.

The aim of our study was to evaluate the effect of hemodialysis by itself on lipid and lipoprotein oxidation profiles and, secondly, to assess whether the antioxidative effect of vitamin C may help prevent atherosclerosis in hemodialysis patients.

Section snippets

Patients

We studied several parameters of lipid antioxidative protection in patients with end-stage renal disease at baseline (before starting chronic hemodialysis) and 1 year after, comparing the results of oral daily treatment with 1 g of vitamin C vs placebo. Some nutritional (serum albumin) and inflammatory (C-reactive protein [CRP]) parameters were recorded.

Forty-one consecutive patients who started hemodialysis in our hospital, in the same year, were enrolled in the study after giving informed

Statistics

Results are expressed as means ± standard deviation (SD). A paired Student-Fisher t test was used to estimate differences between the 2 groups (group A = treated with vitamin C, group B = not treated with vitamin C) before starting hemodialysis therapy and 1 year later. P values < .05 were considered as significant. A descriptive analysis was performed with the SPSS program (SPSS, Chicago, IL).

Results

Lipid profiles improved after a year of hemodialysis therapy (1 year after inclusion) in both groups (vitamin C–treated and nontreated patients)—total cholesterol: 176.4 ± 48.4 to 154.2 ± 28.8 mg/dL (P < .01); LDL cholesterol: 94.1 ± 39.6 to 76.1 ± 26.6 mg/dL (P < .03); and phospholipids levels: 196.5 ± 36.7 to 182.9 ± 36.1 mg/dL (P < .05). The HDL cholesterol was also decreased—49.4 ± 19.8 to 43.4 ± 24.1 mg/dL (P < .03). Serum lipoprotein profiles of both groups are shown in Table 1. There

Discussion

Considering the description of the “elephant in uremia,” Himmelfarb et al [12] propose oxidative stress as a unifying concept of cardiovascular disease in this condition.

Oxidative stress is frequently considered in terms of “total quantity of oxidized products” compared with “total quantity of antioxidants.” As Wratten et al [13] report, this commonly leads to either an underestimation or an overestimation of its physiologic importance.

Several authors [14], [15] have reported an intensification

References (31)

  • A.E.G. Raine et al.

    Mortality from myocardial infarction in patients on renal replacement therapy

    Nephrol Dial Transplant

    (1991)
  • F. Galli et al.

    Pathophysiology of the oxidative stress and its implication in uremia and dialysis

    Contrib Nephrol

    (1999)
  • J.P. Cristol et al.

    Erythropoietin and oxidative stress in haemodialysis: beneficial effects of vitamin E supplementation

    Nephrol Dial Transplant

    (1997)
  • R. Deicher et al.

    Vitamin C in chronic kidney disease and hemodialysis patients

    Kidney Blood Press Res

    (2003)
  • A. Pönka et al.

    Serum ascorbic acid in patients undergoing chronic hemodialysis

    Acta Med Scand

    (1983)
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