Clinical evaluation of performance, biocompatibility, and safety of vitamin E-bonded polysulfone membrane hemodialyzer compared to non-vitamin E-bonded hemodialyzer.

The vitamin E-bonded polysulfone membrane hemodialyzer (ViE™-21) was evaluated in a clinical study for regulatory submission. Seventeen patients on hemodialysis were treated with conventional high-flux hemodialyzers for 2 weeks (Pre-ViE phase) and switched to the ViE-21 for 36 sessions (ViE phase) followed by an additional 2 weeks on conventional hemodialyzers (Post-ViE phase). Reduction ratios of urea, creatinine, beta-2-microglobulin, albumin, and ultrafiltration coefficients (KUF) were measured once during the Pre-ViE phase and twice during the ViE phase. Moreover, biocompatibility markers [leucocyte count, platelet count, and activated complement factor (C3a) levels] were evaluated pre-dialysis, 15 min after initiation, and post-dialysis. During the study, type and number of adverse events (AEs), and device malfunctions were recorded. ViE-21 reduction ratios and KUF were not noticeably different than those of conventional hemodialyzers. Fluctuations of leucocyte counts and C3a concentrations were similar using ViE-21 and conventional hemodialyzers; however, the platelet count fluctuation was lower in ViE-21 sessions. The frequency of episodes of hypotension occurring during the ViE phase was lower than that occurring during the Pre- and Post-ViE phases. In conclusion, this study provided performance and safety data of the ViE-21 for regulatory application. The data suggest that vitamin E-bonded hemodialyzers are beneficial in lowering platelet activation and frequency of intradialytic hypotension. Larger randomized controlled trials are needed to confirm these findings.

Vitamin E as a functional and biocompatibility modifier of synthetic hemodialyzer membranes: an overview of the literature on vitamin E-modified hemodialyzer membranes.

Along with one century of history, research has provided many solutions for hemodialysis (HD) biomaterials, encompassing several generations of copolymers that have found wide application in the development of hollow-fiber dialyzer membranes. Polysulfone-based biomaterials have gained increasing consideration and are now the gold standard in the production of biocompatible hemodialyzers. However, even the highest biocompatibility now available cannot exclude that dialyzer membranes and the overall extracorporeal circulation may produce at the subclinical level immunoinflammatory reactions and thus an increased cardiovascular risk of patients on regular HD therapy. The lipophilic antioxidant and radical scavenger vitamin E has been used (as α-tocopherol) to modify cellulosic and synthetic hollow-fiber membranes with the ultimate goal to neutralize harmful reactive species and to mimic lipid structures of blood cell plasmalemma and lipoprotein particles. Besides filtration and biocompatibility, this modifier has introduced a third function of dialyzer membranes, namely 'antioxidant bioactivity'. Vitamin E can also serve as a template molecule to produce synthetic redox-active and -silent (non-antioxidant) modifiers for future generations of dialyzer membranes. This mini-review article describes the evolution of vitamin E-derived copolymers as a generation of biomaterials that has offered a clinical challenge and still represents a chance to further improving the quality of HD therapy.

Improved management of intradialytic hypotension (IDH) using vitamin E-bonded polysulfone membrane dialyzer.

BACKGROUND: Intradialytic hypotension (IDH) is a common clinical trait in hemodialysis (HD) which is caused by poor biocompatibility of the dialyzer membrane. Aiming to improve IDH, vitamin E-bonded polysulfone dialyzer (VPS-H) was evaluated in a pilot study. METHODS: Eight IDH patients on standard HD were switched from their conventional high-flux dialyzers to VPS-H, and intradialytic blood pressure (BP) was monitored regularly for 10 months. RESULTS: The results showed that hypotension of systolic BP (SBP), diastolic BP (DBP) and pulse pressure (PP) during the session were improved after changing the dialyzer. Notably, almost all the values recorded from 120 minutes into the session until the end of the treatment in the period between the second and tenth month after treatment were significantly different from the corresponding baseline values. Moreover, after 8 to 10 months, the SBP prior to a dialysis session was significantly reduced compared with baseline values. On the other hand, the pulse rate showed no difference throughout the study period. CONCLUSIONS: This study provides early evidence of the beneficial role that vitamin E-bonded dialyzers may have in preventing IDH. Larger controlled trials are needed to confirm this original finding.

Analysis method and characterization of the antioxidant capacity of vitamin E-interactive polysulfone hemodialyzers.

The lipophilic antioxidant vitamin E was used as a surface modifier (or coating agent) of hollow-fiber hemodialyzer membranes with the aim of increasing their biocompatibility and preventing oxidative stress, which are the main clinical drawbacks in hemodialysis (HD) therapy. At present, the redox chemistry of vitamin E-modified dialyzers is not well characterized and there is no standard method to assess the antioxidant capacity of these biomembranes under conditions that simulate those observed during HD therapy. With this study, we developed an original online method to determine the antioxidant capacity of vitamin E-modified dialyzer membranes during circulation experiments. This method is based on a spectrophotometric assay known as the ferric reducing/antioxidant power assay (FRAP). The principle of FRAP and its application to the qualitative and quantitative assessment of miniaturized polysulfone (PS)-based vitamin E-modified dialyzers (PS-VE) were verified by the accurate in vitro analysis of the iron-catalyzed oxidation of vitamin E. The antioxidant capacity of miniaturized PS-VE samples assessed in this study was of 14.5 microM Fe(2+), which corresponded to the transformation of nearly one-third of the vitamin E bound to the hollow-fiber membrane to its oxidation end product alpha-tocopherol quinone. This method shows good reproducibility and intra- and inter-assay precision, and can be easily adapted to determine the redox activity of every type of vitamin E-modified dialyzers during technological investigation, manufacturing control and clinical research.