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NDT Advance Access originally published online on July 22, 2006
Nephrology Dialysis Transplantation 2006 21(10):2825-2833; doi:10.1093/ndt/gfl376
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© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

A systematic review of the effect of the Excebrane dialyser on biomarkers of lipid peroxidation

Marie Anne Sosa1,2, Ethan M. Balk3, Joseph Lau3, Orfeas Liangos1,2,4, Vaidyanathapuram S. Balakrishnan4, Nicolaos E. Madias1,2,4, Brian J. G. Pereira4 and Bertrand L. Jaber1,2,4,

1Department of Medicine, Tufts University School of Medicine 2Division of Nephrology, Caritas St Elizabeth's Medical Center 3Institute for Clinical Research and Health Policy Studies and 4Division of Nephrology, Tufts-New England Medical Center, Boston, MA, USA

Correspondence and offprint requests to: Bertrand L. Jaber, MD, Department of Medicine, Caritas St. Elizabeth's Medical Center 736 Cambridge Street, Boston, MA 02135, USA. Email: bertrand.jaber{at}caritaschristi.org



   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
Background. Oxidative stress is prevalent in dialysis patients and has been implicated in the pathogenesis of cardiovascular disease and anaemia. We conducted a systematic review and meta-analysis to examine the effect of Excebrane, a vitamin E-coated cellulose-based dialyser, on circulating biomarkers of lipid peroxidation, as surrogate markers of oxidative stress.

Methods. The primary sources used to identify candidate studies included PubMed, the Cochrane Central Register of Controlled Trials, a bibliography provided by the dialyser manufacturer, and a manual search of abstracts from proceedings of scientific meetings and review articles. Studies were selected for analysis if their design included a comparator group (primarily within patient comparison, i.e. pre- and post-study evaluations). For the meta-analysis, we computed the overall change of the outcome from baseline using a random-effects model. A supplemental analysis was performed in which the absolute levels of these biomarkers of lipid peroxidation were converted to a common unit by calculating standardized effect sizes.

Results. Fourteen peer-reviewed articles met the criteria. The studies consisted of 11 single arm, one randomized crossover and two randomized controlled trials, with a total of 37 to 158 evaluable patients, according to the outcome of interest analysed. Due to the paucity of randomized trials, the meta-analysis was limited to the Excebrane arm of each study. When the studies were combined according to similar measurement units, the overall mean decrease in malondialdehyde (MDA) level was -0.3 mM (95% CI, –0.5 to –0.1 mM; seven studies) and –0.8 nmol/mg low-density lipoprotein (LDL) (95% CI, –1.3 to –0.4 nmol/mg LDL; three studies), respectively. The summary estimate revealed a non-significant decrease in pre-dialysis thiobarbituric acid reactive substances (TBARS) level of 0.4 µM (95% CI, –1.2 to 0.4 µM; three studies). When the MDA and TBARS studies were combined using the standardized effect size, the mean decrease in these biomarkers of lipid peroxidation was statistically significant at –1.7 units (95% CI, –2.7, –0.7 units; 13 studies). A meta-analysis on the effect of Excebrane on pre-dialysis levels of oxidized-LDL could not be performed due to study heterogeneity.

Conclusion. The conversion of dialysis patients to a vitamin E-coated dialyser is associated with an improvement in circulating biomarkers of lipid peroxidation, which is of potential clinical benefit.

Keywords: cardiovascular disease; Excebrane; haemodialysis; lipid peroxidation; meta-analysis; oxidative stress; vitamin E



   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
Evidence for increased oxidative stress in dialysis patients was first reported in 1984 [1,2]. Following these early reports, there has been a sustained growth of interest in documenting oxidative stress in dialysis patients. Available evidence suggests that the balance between pro- and anti-oxidant capacities is shifted towards increased oxidative stress in dialysis patients [3–5]. Factors contributing to increased pro-oxidant activity include advanced age, diabetes mellitus, uraemia, chronic inflammation, malnutrition and factors associated with the dialysis treatment per se. Indeed, the low-biocompatibility of haemodialysis membranes results in the activation of oxidative reactions, which increases the generation of oxygen free radicals [6]. In addition, several deficiencies in different components of antioxidant defence mechanisms have been demonstrated in dialysis patients, including reduced levels of circulating vitamin C as well as intracellular vitamin E and selenium, and deficiency in the glutathione scavenging system [3,4]. Finally, the administration of parenteral iron preparations to anaemic patients during dialysis can increase the generation of oxygen free radicals, leading to the formation of lipid peroxides [7].

Oxidative stress has been incriminated in the pathogenesis of cardiovascular disease in dialysis patients [8]. Because oxidants have very short half-lives, in vivo determination is generally not feasible. Therefore, the working group of the National Kidney Foundation's (NKF) K/DOQI Clinical Practice Guidelines for Cardiovascular Disease in Dialysis Patients recommended that the determination of oxidative stress should rely on the use of more stable surrogate biomarkers. Such biomarkers include lipids, proteins, carbohydrates and nucleic acids that are modified by oxygen radicals and have lifetimes ranging from hours to weeks [8].

Given the evidence that supports the role of oxidative stress in cardiovascular morbidity in dialysis patients, antioxidant strategies have been adopted to combat oxidative stress. In the haemodialysis population, as the interaction between dialysis membranes and blood neutrophils can trigger oxidative stress [9,11], direct scavenging of free radicals at the dialysis membrane site is an attractive therapeutic approach. Thus, specific dialysis membranes have been introduced in an attempt to reduce oxidative stress. Excebrane is one such membrane and consists of a multi-layer membrane modified on the blood surface to support a coating of the liposoluble physiological antioxidant vitamin E [12–15]. In the past decade, numerous studies have been conducted to assess the effect of this vitamin E-coated dialyser on biomarkers of oxidative stress. Most of these studies were small in size and might have lacked sufficient statistical power to address the issue adequately. To overcome some of these limitations, we conducted a systematic review and meta-analysis to examine the effect of the Excebrane dialyser on circulating biomarkers of lipid peroxidation, as surrogate markers of oxidative stress.



   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
Search for relevant studies
The primary sources used to identify clinical studies included (i) a literature search in PubMed using the search terms ‘dialysis’, ‘hemodialysis’, ‘renal replacement therapy’ and ‘vitamin E’, limited to clinical trials on humans published through May 2005; (ii) a literature search in the Cochrane Central Register of Controlled Trials, using the same search terms over the same time period; (iii) a bibliography provided by the manufacturer of the Excebrane dialyser (Asahi Kasei Medical Co., Ltd, Tokyo, Japan) and (iv) a manual search of proceedings of the annual meetings of the American Society of Nephrology (1999–2005), review articles and study references. Non-English language studies were excluded.

Study selection and data abstraction
Two independent reviewers (M.S. and B.L.J.) evaluated the abstracts for relevance to the study topic. Prospective, longitudinal studies of patients receiving haemodialysis with the Excebrane dialyser were selected, and the data were extracted if they examined the impact of the Excebrane dialyser on changes in circulating pre-dialysis biomarkers of lipid peroxidation, including malondialdehyde (MDA), thiobarbituric acid reactive substances (TBARS) and oxidized-low-density lipoprotein (Ox-LDL). These biomarkers of lipid peroxidation were selected because they have been well-studied and have been recommended for use to assess oxidative stress in dialysis patients [8]. The laboratory methods used to determine the levels of these biomarkers were also evaluated. Studies were selected for analysis if their design included a comparator group (primarily within patient comparison, i.e. pre- and post-study evaluations). No restrictions were placed on minimal study duration or sample size. Cross-sectional studies with a single estimate of the aforementioned outcomes of interest were excluded.

Statistical methods
We performed meta-analyses to evaluate the change of the outcome from baseline. Meta-analyses were performed using a random-effects model, which assigns a weight to each study based on both the within-study variance and the between-study heterogeneity [16]. When necessary, the standard error of the change from baseline was estimated from the reported variances of baseline and final values or from the available individual patient data [17]. For Ox-LDL, a meta-analysis was not performed because the studies were so heterogeneous that a single overall estimate was not a meaningful measure of the effect.

Because of the relatively small number of controlled studies, meta-analyses were performed on the data from the uncontrolled single cohorts (i.e. before vs after dialyser change), regardless of the study design. Thus, the analyses were restricted to changes from the pre-dialysis values only in patients whose dialysers were changed to Excebrane. In an attempt to explain heterogeneity, sensitivity analyses were performed with exploratory sub-group analyses and meta-regression.

Since TBARS and the two measurement methods for MDA all quantitate the same process but use different units, a supplemental analysis was performed in which the absolute levels of these biomarkers of lipid peroxidation were converted to a common unit by calculating standardized effect sizes [18,19]. The standardized effect size is a dimensionless metric that provides an estimate of the magnitude of an effect; it has been used to combine data where similar outcomes were reported using different units of measurement [20–22]. The standardized effect size was derived by dividing the mean change in each biomarker level by its standard deviation. The variance of the standardized effect size was estimated by the inverse of the sample size.



   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
Overall characteristics of selected studies
The initial literature search returned 459 citations, 269 from PubMed, 57 from the Cochrane database and 133 from the Excebrane dialyser manufacturer, as well as five scientific abstracts from the proceedings of the annual meetings of the American Society of Nephrology. A total of 93 citations met the initial screening criteria and were retrieved and evaluated. Out of those, 79 studies were excluded for the following reasons: 12 studies examined the effect of oral vitamin E supplementation, 20 studies focused on the biocompatibility of the Excebrane dialyser (including leucocyte activation markers, cytokines, soluble adhesions molecules, ß-2 microglobulin and coagulation factors), 18 citations were review articles, editorials or case reports, six studies documented changes exclusively in pre-dialysis haemoglobin level and/or recombinant human erythropoietin (rHuEpo) dosing requirement, 15 studies measured biomarkers of oxidative stress in the dialysis population, two citations were animal studies, and one report concentrated on healthy individuals. Finally, six studies examining the effect of the Excebrane dialyser on biomarkers of oxidative stress were excluded because values were either documented after one single dialysis (no long-term pre-dialysis changes), single arm values were simply not documented, or where improvements were noted but not documented.

Fourteen remaining studies met the study criteria [23–36]. The characteristics of the individual studies and outcome measures are summarized in Table 1. In brief, the studies consisted of 11 single arm studies [23,24,26–29,31,33–36], one randomized crossover study [32] and two randomized trials [25,30]. Circulating MDA was measured in 10 [23–25, 29–34,36], TBARS in three [26–28] and Ox-LDL in four [25,30,32,35] studies. The overall duration of individual studies ranged from 3 weeks to 24 months. Duration of dialysis ranged from 1.5 to 17 years. Male gender distribution ranged from 31 to 70%. Mean age ranged from 43 to 75 years. Causes of end-stage renal disease were documented in 9 of the 14 studies [27–30,3–36], and included glomerulonephritis (30–90%), chronic interstitial nephritis (7–38%), nephrosclerosis (6–50%), polycystic kidney disease (8–18%) and diabetic nephropathy (8–17%). Notably, 9 of the 14 studies excluded diabetic patients [23,25–27,29,30,32–34], and one study did not document the presence of diabetes [24]. In the remaining four studies, the prevalence of diabetes ranged between 8 and 44% [28,31,35,36]. Sample size of individual studies ranged from 10 to 50, with a total of 37 to 58 evaluable patients, according to the outcome measure of interest analysed.


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  		Table 1. Study characteristics and outcome measures

 
Characteristics of the dialyser membranes used in the individual studies are summarized in Table 2. In brief, the baseline dialysers were made of cellulose or synthetic polymers with a mix of low- and high-flux membranes. The Excebrane dialysers also consisted of either low- or high-flux membranes. Conclusions drawn in the individual studies on the effect of the Excebrane dialyser on lipid peroxidation biomarkers are summarized in Table 3.


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  		Table 2. Dialyser characteristics of studies included in the present systematic review

 

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  		Table 3. Conclusions drawn from the individual studies on the effect of the Excebrane dialyser on changes in pre-dialysis biomarkers of lipid peroxidation

 
Effect of the Excebrane dialyser on biomarkers of lipid peroxidation
Malondialdehyde (MDA) studies
There were 10 studies (containing 11 study arms) with analysable data for MDA, which included 121 evaluable patients (Table 3, Figure 1) [23–25,29–33,34,36]. These included seven single-arm studies [23,24,29,31,33,34,36], one randomized crossover study [32], and two randomized trials [25,30]. Four studies were performed in Japan [25,30–32], and six in Europe [23,24,29,33,34,36]. Mean patient ages ranged from 43 to 70 years, and patients were on dialysis for at least 1.5 years in all studies. Study durations ranged from 3 weeks to 2 years.


Figure 1
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  		Fig. 1. Effect of the Excebrane dialyser on pre-dialysis malondialdehyde (MDA) and Thiobarbituric Acid Reactive Substances (TBARS) levels. The meta-analysis was performed using the random effects model. (A) and (B) display changes in pre-dialysis mean MDA levels from baseline, for studies where this biomarker was reported in mM and nmol/mg LDL, respectively. (C) displays changes in pre-dialysis mean TBARS levels (µM) form baseline. (D) displays changes in pre-dialysis lipid peroxidation biomarker levels from baseline, using the standardized effect size. All the data are presented as mean changes with 95% CI.

 
The methods for determining MDA are summarized in Table 4, and include primarily spectrofluorometry and high-performance liquid chromatography (HPLC). The MDA values were reported in two non-convertible units; consequently, these studies were analysed both separately and with standardized effect sizes.


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  		Table 4. Methods used for measuring biomarkers of lipid peroxidation in the individual studies

 
Seven studies reported statistically significant reductions in pre-dialysis MDA levels from baseline (Table 3, Figure 1A and B) [23,29,30,32–34,36]. Satoh et al. [31] stratified the analyses according to diabetic status, demonstrating significant improvement in pre-dialysis MDA levels only in diabetic patients. Mune et al. [25] did not observe significant improvement in pre-dialysis MDA levels by the end of the study period, however, significance was attained only when comparisons were made between the baseline and the end-of-study post-dialysis MDA levels (6.0 vs 4.2 nmol/mg LDL) [25].

When the studies were combined according to similar measurement units, the overall mean decrease in MDA level was –0.3 mM (95% CI, –0.5 to –0.1 mM; seven studies; Figure 1A) and –0.8 nmol/mg LDL (95% CI, –1.3 to –0.4 nmol/mg LDL; three studies; Figure 1B), respectively. In a sensitivity analysis excluding the study by Buoncristiani et al. [23], which reported extremely low-baseline values compared with the other studies, the summary estimate of the mean decrease in MDA level was unchanged. In a sensitivity analysis including all the studies reporting MDA level regardless of units, the mean decrease in MDA level was statistically significant at –1.4 standardized effect size units (95% CI, –2.3, –0.5 units; 10 studies; Figure 1D).

Thiobarbituric Acid Reactive Substances (TBARS) studies
There were three studies from Europe with analysable data for TBARS [27,28,37]. All three studies had a single-arm design with a total of 37 evaluable patients. Mean patient ages ranged from 44 to 65 years with mean durations of dialysis ranging from 3 months to 2.6 years. The studies lasted from 1 to 3 months. Two studies excluded diabetic patients [27]. The methods for determining TBARS were reported in all three studies and are summarized in Table 4.

The results were significant in two studies (Table 3, Figure 1C) [27,28]. Notably, in one study with non-significant results by Bonnefont-Rousselot et al. [26], patients were younger and had been on dialysis for a shorter duration. In addition, this study was the only one to use high-flux dialysers, which might have also confounded the results.

The summary estimate of all the three studies revealed a non-significant decrease in pre-dialysis TBARS level of –0.4 µM (95% CI, –1.2 to 0.4 µM). In a sensitivity analysis excluding the study by Galli et al. [27], which had reported extremely low baseline values, the overall mean decrease in pre-dialysis TBARS level was similar (–0.6 µM, 95% CI, –1.4 to 0.2 µM).

Combined MDA and TBARS studies
When the MDA and TBARS studies were combined using the standardized effect size, the mean decrease in these biomarkers of lipid peroxidation was statistically significant at –1.7 units (95% CI, –2.7, –0.7 units; 13 studies; Figure 1D).

Oxidized-LDL (Ox-LDL) studies
There were four studies with analysable data for Ox-LDL (Table 3, Figure 2) [25,30,32,35]. One study had a single-arm design [35], one study a randomized crossover design [32] and two were randomized controlled trials [25,30], from which only the Excebrane intervention arm data were extracted for the current analyses, totalling 54 evaluable patients. Mean patient ages ranged from 55 to 62 years, and patients were on dialysis for 7–13 years. Study durations ranged from 4 to 24 months. Two studies excluded diabetic patients [32], whereas one study did not provide information on diabetes status [25]. As shown in Table 4, Ox-LDL was measured by enzyme linked immunosorbent assay in all four studies, according to the method by Itabe et al. [38,39].


Figure 2
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  		Fig. 2. Effect of the Excebrane dialyser on pre-dialysis Ox-LDL levels. *Although Shimazu et al. [30] reported a statistically significant decrease in mean Ox-LDL levels, this figure was drawn using an estimate of the SE of change, which was derived from reported SDs of baseline and final values. If a greater correlation between baseline and final SEs were assumed, the estimated 95% CI would be statistically significant.

 
The changes from the baseline were significant in two studies (Table 3, Figure 2) [30,32]. In the remaining two studies [25,35], the results were significant only when baseline post-dialysis Ox-LDL levels were compared with values obtained in the immediate post-dialysis period. Overall, the studies had a high degree of heterogeneity, such that Mune et al. [25] and Hara et al. [35] found a non-significant small increase and small reduction in pre-dialysis Ox-LDL levels, respectively, whereas Tsuruoka et al. [32] and Shimazu et al. [30] found a highly significant reduction in pre-dialysis Ox-LDL levels. The four studies were of such great statistical heterogeneity that the meta-analysis did not provide a meaningful measure of the overall effect.

Sensitivity analyses
In an attempt to explain heterogeneity, sensitivity analyses were performed with exploratory sub-group analyses and meta-regression. An analysis examining the effect of baseline measurements on changes in each outcome variable yielded no association, and is therefore not presented. Meta regression analyses exploring the relationship of study duration, mean patient age and mean dialysis duration with changes in the biomarkers of lipid peroxidation, also yielded no significant associations.



   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
Oxidative stress is highly prevalent in dialysis patients. It has been implicated in the pathogenesis of cardiovascular disease and anaemia, and might contribute to increased morbidity and mortality [3,4]. In the haemodialysis population, there is a well-known interaction between the dialysis membrane and circulating blood neutrophils, which triggers the release of oxygen-free radicals and oxidizing agents, such as superoxide anion, hydrogen peroxide and myeloperoxidase [6]. In turn, these molecules contribute to the oxidation of lipid byproducts, proteins and nucleic acids [9–11,40]. This oxidation has several pathophysiological consequences, including enhanced atherogenicity of Ox-LDL [41], as well as accelerated demise of circulating erythrocytes, leading to a shorter life span [8]. Consequently, the direct scavenging of free radicals through the use of oral vitamin E is an attractive therapeutic strategy. This can be achieved broadly by using oral vitamin E supplementation [42,43], or more specifically, by binding vitamin E to the dialysis membrane site. The latter technological approach led to the development of Excebrane, a vitamin E-coated cellulose-based dialyser.

In this systematic review and meta-analysis, prevalent dialysis patients who converted from cellulose- or synthetic polymer-based dialysers to Excebrane had significant decreases in the two circulating biomarkers of lipid peroxidation, MDA and TBARS, which were in the order of –1.7 standardized effect size units. These results are of potential importance in light of the role of oxidative stress in cardiovascular morbidity in dialysis patients.

The varying conclusions drawn from individual studies examined in this meta-analysis might result from insufficient sample size, a lack of standardization of biomarker assays and a lack of control for confounders. Additional sources of variability include the differences in patient age, comorbid conditions, such as diabetes, dialysis membrane characteristics (e.g. surface area, efficiency and flux property), adequacy of dialysis and follow-up duration.

There are several limitations regarding the evidence presented in this meta-analysis that should be emphasized. Due to the paucity of randomized controlled trials, this review primarily evaluates observational studies. With the use of single-arm studies, a ‘regression towards the mean’ phenomenon is a concern. To illustrate this common problem, if one is interested in the relationship between the initial value of a measurement and the change in that quantity over time, the normal fluctuation in the measurement can by chance decline or increase over time irrespective of treatment intervention. This is particularly salient in single-arm studies where a valid control group is not available to capture the measurement errors that can occur over time.

In the absence of studies comparing the effect of Excebrane directly with other dialysers, the conclusions remain, at best, hypothesis generating. In addition, heterogeneity in the sample population was present across all studies, due, in part, to differences in selection of participants. Examples included differences in mean patient age, dialysis vintage, prevalence of diabetes and dialyser flux properties. Also, as noted earlier, numerous measurement techniques were used across studies. When possible, we attempted to overcome this problem by using the standardized effect size in the meta-analyses. Although this metric has been validated and is frequently found in education and social science literature, its use in the medical literature has been limited because of the difficulties in interpreting the results of this dimensionless metric.

The biological validity of this approach also merits further discussion. While the TBARS assay is considered a global test for assessing lipid peroxidation, the MDA assay is more specific for measuring a particular endproduct formed during oxidative stress. Indeed, MDA is one of the several products formed during the radical induced decomposition of polyunsaturated fatty acids [44,45]. Further research is needed to determine which oxidative stress pathway (i.e. nitrosative, chlorinated or carbonyl stress) is quantitatively more important in patients with kidney failure. It is worth noting, however, that for any experimental circulating biomarker to be measured correctly, issues about pre-analytical and analytical variation must be better understood, and guidance must be provided to minimize their effect on test results [46]. Pre-analytical factors include variation from physiological variables such as race, age, gender, season and lifestyle, and from specimen collection variables such as fasting, collection time, specimen type and storage. Whereas some of these factors have been addressed for instance with measurement of C-reactive protein, a biomarker of inflammation [46], no such comprehensive approach has been conducted for biomarkers of oxidative stress.

Finally, MDA and TBARS are not perfect measures of oxidative stress even though they have been recommended by the NKF guidelines. At the present time, these biomarkers remain, at best, research tools. According to a recent study in the US, the Agency for Healthcare Research and Quality Technology Assessment Program has adopted a six-level framework for evaluating diagnostic technologies [47]. Based on these rigorous steps, the validity of any biomarker of oxidative stress would require the performance of additional studies aimed at addressing technical feasibility, diagnostic accuracy and the impact of test result on health outcomes. Unfortunately, the present meta-analysis is unable to address the test performance of the various biomarkers of oxidative stress.

To better characterize the order of magnitude of the membrane's effect on MDA levels and to allow for estimation of a potential biological relevance, in a recently published report on oxidant stress status in humans, mean serum MDA level measured in 31 young (mean age 24 years) and 45 elderly (mean age 71 years) healthy individuals (all non-smokers) was 0.22 and 0.23 mM, respectively [48]. In our meta-analysis, excluding the one study by Buoncristiani (Figure 1, panel A), the weighted mean baseline MDA level was 2.4 mM, which is 10–11-fold higher than the aforementioned values observed in healthy individuals. The overall mean decrease in MDA level in our analysis was -0.3 mM (95% CI, -0.5 to –0.1 mM), which translates into a 12.5% decline (95% CI, -21%, -4%).

Notably, the potential funding source bias does not appear to have skewed the results as only two studies documented support by the dialyser manufacturer. However, we cannot ascertain whether other investigators were sponsored by the manufacturer but failed to disclose this information in their published report.

Although there is paucity of direct evidence supporting the role of the Excebrane dialyser in combating oxidative stress, this systematic review and meta-analysis provide the best summary of the evidence compiled to date on the biological effects of a relatively novel dialysis membrane coated with vitamin E to scavenge oxygen free radicals generated during dialysis. In addition to combating oxidative stress, several studies have examined the effect of the Excebrane dialyser on surrogate measures of vascular biology, primarily vascular calcification, T-cell activation, production of pro-inflammatory cytokines, and up-regulation of leucocyte adhesion molecules [25,49,50]. We can only speculate as to whether the development of a synthetic polymer-based dialyser coated with vitamin E would result in a further improvement in oxidative stress, compared with the cellulose-based Excebrane membrane. In fact, a recent report on the long-term use of such a dialyser (manufactured by the same company) over an 18-month period demonstrated a robust 25–30% reduction in plasma levels of MDA and Ox-LDL [51]. Additional studies are needed to confirm these encouraging preliminary findings.

In summary, this systematic review and meta-analysis of single-arm studies suggest that the conversion of patients on maintenance haemodialysis to a vitamin E-coated dialyser is associated with an improvement in circulating biomarkers of lipid peroxidation, which is of potential clinical benefit. Randomized controlled trials aimed at comparing the effect of the Excebrane dialyser with a traditional synthetic polymer-based dialyser on biomarkers of lipid peroxidation as well as on more meaningful cardiovascular endpoints, are warranted.



   Acknowledgments
 
B.L.J. is supported by a grant from the National Institutes of Health (DK065102). O.L. is supported by a grant from the American Heart Association (AHA #0535367N). The authors wish to thank Masaharu Aritomi, PhD (International Business Department, Blood Purification Division, Asahi Kasei Medical Co., Ltd, Tokyo, Japan) for providing the Excebrane dialyzer manufacturer's bibliography.

Conflict of interest statement. None declared.



   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

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Received for publication: 14. 2.06
Accepted in revised form: 30. 5.06


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