Lipoperoxidation and hemodialysis
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
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