Galli Dovepress Actually, since from the first researches by us and other a series of promising small clinical studies that examined groups in the late 1990s, it was clear that the clinical effects aortic calcifications,21 carotid atherosclerosis17,22 and the nitric of these membranes could not be explained simply with the oxide-dependent vasodilation response during HD.23 concept that the chromanols bound to the dialysis membrane In conclusion, it is my belief that all these effects and the surface may produce an in vivo scavenging effect on peroxyl efforts made by the authors to explain them in this review radicals, ie, producing an antioxidant therapy effect. paper can be summarized in the concept of “superior biocom- In other words, the antioxidant activity as well as the patibility” that these vitamin E-modified membranes may have other beneficial properties of this vitamin E (bound to the with respect to several other dialyser membranes particularly dialyser membranes), are probably different from those of in the recent interactive polysulfone-based version. the vitamin E form introduced with the diet or supplements, which is present in the circulation within the lipoprotein particles and in the cell membranes. Thus, the interpretation of possible therapeutic mecha- nisms by these modified membranes needs more careful dissection and further studies aimed to verify underlying events. To explain the benefical effects of these membranes reported in literature, they have used expressions such as “pharmacokinetic factors”, “the type of the α-T molecule used”, “form of the drug” or “pharmacokinetic conditions”, which are obviously inappropriate in this context and may generate confusion in the readers. In the case of these membranes, indeed, the form of vitamin E that should be taken into account is exclusively that present in synthetic coating on the blood surface of the hollow fiber, ie, all-rac-α-tocopherol, and this vitamin E form does not seem to be released even under drastic in vitro recirculation conditions.7 Thus, there is no reason to discuss clinical effects of vitamin E-modified membrane dialysers in terms of “pharmacokinetics”. As Kirmizis and Chatzidimitriou briefly discussed in their review paper, the antioxidation and anti-inflammatory protection claimed in several studies on these membranes are probably the result of a complex series of effects. Accord- ing to the available evidence in literature already reviewed by us8,9 and others,10 even the previous generations of less biocompatible (cellulosic) vitamin E-modified hemodialyser membranes were observed to produce a better control of antioxidant parameters and lowered oxidative stress mark- ers,11–14 but at the same time these membranes were found to provide a better control of leukocyte activation and apoptotic death,8,15,16 of erythrocyte integrity and lifespan,17,18,a and to afford higher protection of low-density lipoproteins and endo- thelial cells.19,20 Probably, the interaction of all these effects is responsible for the improved CVD outcome observed in aThese membranes have been considered as one of the therapeutic tools in the guidelines for anemia management in chronic renal failure patients (published in Nephrol Dial Transplant. 2008;Suppl 2:N.19). 70 submit your manuscript | www.dovepress.com Dovepress Disclosure References The author reports no conflicts of interest in this letter. 1. Boaz M, Smetana S, Weinstein T, et al. Secondary prevention with antioxidants of cardiovascular disease in endstage renal disease (SPACE): randomised placebo-controlled trial. Lancet. 2000; 356:1213–1218. 2. Galli F, Buoncristiani U, Conte C, Aisa C, Floridi A. Vitamin E in uremia and dialysis patients. Ann N Y Acad Sci. 2004;1031:348–351. 3. Galli F, Floridi AG, Floridi A, Buoncristiani U. Accumulation of vitamin E metabolites in the blood of renal failure patients. Clin Nutr. 2004;23:205–212. 4. Galli F, Azzi A. BioFactors (Oxford, England). In press. 5. Galli F, Cristina Polidori M, Stahl W, Mecocci P, Kelly FJ. Vitamin E biotransformation in humans. Vitam Horm. 2007; 76:263–280. 6. Buoncristiani U, Galli F, Rovidati S, et al. Oxidative damage during hemodialysis using a vitamin-E-modified dialysis membrane: a pre- liminary characterization. Nephron. 1997;77:57–61. 7. Floridi A, Piroddi M, Pilolli F, et al. Analysis method and characteriza- tion of the antioxidant capacity of vitamin E-interactive polysulfone hemodialyzers. Acta Biomater. 2009;5:2974–2982. 8. Galli F, Canestrari F, Buoncristiani U. Biological effects of oxidant stress in haemodialysis: the possible roles of vitamin E. Blood Purif. 1999;17:79–94. 9. Galli F. Vitamin E-modified dialyzers. Contrib Nephrol. 2002;(137): 95–105. 10. Sosa MA, Balk EM, Lau J, et al. A systematic review of the effect of the Excebrane dialyser on biomarkers of lipid peroxidation. Nephrol Dial Transplant. 2006;21:2825–2833. 11. Morimoto H, Nakao K, Fukuoka K, et al. Long-term use of vita- min E-coated polysulfone membrane reduces oxidative stress mark- ers in haemodialysis patients. Nephrol Dial Transplant. 2005; 20:2775–2782. 12. Galli F, Rovidati S, Chiarantini L, et al. Bioreactivity and biocompat- ibility of a vitamin E-modified multi-layer hemodialysis filter. Kidney Int. 1998;54:580–589. 13. Clermont G, Lecour S, Cabanne JF, et al. Vitamin E-coated dialyzer reduces oxidative stress in hemodialysis patients. Free Radic Biol Med. 2001;31:233–241. 14. Galli F, Rovidati S, Benedetti S, et al. Lipid peroxidation, leukocyte function and apoptosis in hemodialysis patients treated with vitamin E-modified filters. Contrib Nephrol. 1999;127:156–171. 15. Betjes MG, Hoekstra FM, Klepper M, Postma SM, Vaessen LM. Vitamin E-coated dialyzer membranes downregulate expression of monocyte adhesion and co-stimulatory molecules. Blood Purif. 2004; 22:510–517. 16. Girndt M, Lengler S, Kaul H, Sester U, Sester M, Köhler H. Prospective crossover trial of the influence of vitamin E-coated dialyzer membranes on T-cell activation and cytokine induction. Am J Kidney Dis. 2000;35:95–104. Vascular Health and Risk Management 2010:6