Oxidative stress is prevalent in end-stage kidney disease patients receiving chronic hemodialysis and is associated with heavy cardiovascular disease burdens and increased mortality risks. Hemoincompatible hemodialysis membranes per se contribute to the activation of oxidative reactions and the generation of oxygen free radicals. Since the early 1990s, vitamin E-coated membranes have been extensively used in hemodialysis patients to reduce oxidative stress during hemodialysis sessions. However, the beneficial effects of vitamin E-coated membranes versus unmodified synthetic membranes on long-term patient-centered outcomes, such as survival, quality of life, and prevalence of cardiovascular diseases, remain controversial. Accordingly, novel antioxidant hemodialysis membranes were prepared to replace the use of vitamin E-coated membranes despite the translational research on these membranes unfortunately coming to a standstill. In this review, we first summarize the state-of-the-art on the use of vitamin E-coated membranes in hemodialysis patients to highlight their strengths and limitations. Then, we discuss the latest advances in fabricating antioxidant hemodialysis membranes and provide perspectives to bridge knowledge gaps between laboratorial investigations and clinical practice in fabricating antioxidant hemodialysis membranes.

Basile C, Davenport A, Mitra S, Pal A, Stamatialis D, Chrysochou C, et al. Frontiers in hemodialysis: innovations and technological advances. Artif Organs. 2021;45(2):175–82.
Zhang Z, Yang T, Li Y, Li J, Yang Q, Wang L, et al. Effects of expanded hemodialysis with medium cut-off membranes on maintenance hemodialysis patients: a review. Membranes. 2022;12(3):253.
Canaud B. Recent advances in dialysis membranes. Curr Opin Nephrol Hypertens. 2021;30(6):613–22.
Liakopoulos V, Roumeliotis S, Zarogiannis S, Eleftheriadis T, Mertens PR. Oxidative stress in hemodialysis: causative mechanisms, clinical implications, and possible therapeutic interventions. Semin Dial. 2019;32(1):58–71.
Duni A, Liakopoulos V, Rapsomanikis KP, Dounousi E. Chronic kidney disease and disproportionally increased cardiovascular damage: does oxidative stress explain the burden?Oxid Med Cel Longev. 2017;2017:9036450.
Liakopoulos V, Roumeliotis S, Gorny X, Dounousi E, Mertens PR. Oxidative stress in hemodialysis patients: a review of the literature. Oxid Med Cel Longev. 2017;2017:3081856.
Hirayama A, Akazaki S, Nagano Y, Ueda A, Chang-Il Lee M, Aoyagi K, et al. Hemodialysis raises oxidative stress through carbon-centered radicals despite improved biocompatibility. J Clin Biochem Nutr. 2021;69(1):44–51.
Nguyen AT, Lethias C, Zingraff J, Herbelin A, Naret C, Descamps-Latscha B. Hemodialysis membrane-induced activation of phagocyte oxidative metabolism detected in vivo and in vitro within microamounts of whole blood. Kidney Int. 1985;28(2):158–67.
Piroddi M, Pilolli F, Aritomi M, Galli F. Vitamin e as a functional and biocompatibility modifier of synthetic hemodialyzer membranes: an overview of the literature on vitamin e-modified hemodialyzer membranes. Am J Nephrol. 2012;35(6):559–72.
D’Arrigo G, Baggetta R, Tripepi G, Galli F, Bolignano D. Effects of vitamin e-coated versus conventional membranes in chronic hemodialysis patients: a systematic review and meta-analysis. Blood Purif. 2017;43(1–3):101–22.
Zaman SU, Rafiq S, Ali A, Mehdi MS, Arshad A, Rehman SU, et al. Recent advancement challenges with synthesis of biocompatible hemodialysis membranes. Chemosphere. 2022;307(Pt 2):135626.
Yang CC, Hsu SP, Wu MS, Hsu SM, Chien CT. Effects of vitamin c infusion and vitamin e-coated membrane on hemodialysis-induced oxidative stress. Kidney Int. 2006;69(4):706–14.
Kirmizis D, Papagianni A, Belechri AM, Memmos D. Effects of vitamin e-coated membrane dialyser on markers of oxidative stress and inflammation in patients on chronic haemodialysis. Nephrol Dial Transplant. 2011;26(7):2296–301.
Panichi V, Rosati A, Paoletti S, Ferrandello P, Migliori M, Beati S, et al. A vitamin e-coated polysulfone membrane reduces serum levels of inflammatory markers and resistance to erythropoietin-stimulating agents in hemodialysis patients: results of a randomized cross-over multicenter trial. Blood Purif. 2011;32(1):7–14.
Rodríguez-Ribera L, Corredor Z, Silva I, Díaz JM, Ballarín J, Marcos R, et al. Vitamin e-coated dialysis membranes reduce the levels of oxidative genetic damage in hemodialysis patients. Mutat Res Genet Toxicol Environ Mutagen. 2017;815:16–21.
Yang SK, Xiao L, Xu B, Xu XX, Liu FY, Sun L. Effects of vitamin e-coated dialyzer on oxidative stress and inflammation status in hemodialysis patients: a systematic review and meta-analysis. Ren Fail. 2014;36(5):722–31.
Huang J, Yi B, Li AM, Zhang H. Effects of vitamin e-coated dialysis membranes on anemia, nutrition and dyslipidemia status in hemodialysis patients: a meta-analysis. Ren Fail. 2015;37(3):398–407.
Bargnoux AS, Cristol JP, Jaussent I, Chalabi L, Bories P, Dion JJ, et al. Vitamin e-coated polysulfone membrane improved red blood cell antioxidant status in hemodialysis patients. J Nephrol. 2013;26(3):556–63.
Cruz DN, de Cal M, Ronco C. Oxidative stress and anemia in chronic hemodialysis: the promise of bioreactive membranes. Contrib Nephrol. 2008;161:89–98.
Zhang Y, Gao W, Li X. Vitamin e-coated dialyzer alleviates erythrocyte deformability dysfunction in patients with end-stage renal disease undergoing hemodialysis. Exp Ther Med. 2022;24(1):480.
Mandolfo S, Corradi B, Bucci R, Farina M, Pilolli F, Galli F. Evaluation of the impact of a new synthetic vitamin e-bonded membrane on anemia and rhuepo requirement in esrd patients with central venous catheters: a pilot study. Int Urol Nephrol. 2012;44(5):1493–500.
Locatelli F, Andrulli S, Viganò SM, Concetti M, Urbini S, Giacchino F, et al. Evaluation of the impact of a new synthetic vitamin e-bonded membrane on the hypo-responsiveness to the erythropoietin therapy in hemodialysis patients: a multicenter study. Blood Purif. 2017;43(4):338–45.
Sanaka T, Mochizuki T, Kinugasa E, Kusano E, Ohwada S, Kuno T, et al. Randomized controlled open-label trial of vitamin e-bonded polysulfone dialyzer and erythropoiesis-stimulating agent response. Clin J Am Soc Nephrol. 2013;8(6):969–78.
Lines SW, Carter AM, Dunn EJ, Lindley EJ, Tattersall JE, Wright MJ. A randomized controlled trial evaluating the erythropoiesis stimulating agent sparing potential of a vitamin e-bonded polysulfone dialysis membrane. Nephrol Dial Transplant. 2014;29(3):649–56.
Huraib S, Tanimu D, Shaheen F, Hejaili F, Giles C, Pagayon V. Effect of vitamin-e-modified dialysers on dialyser clotting, erythropoietin and heparin dosage: a comparative crossover study. Am J Nephrol. 2000;20(5):364–8.
Aoun B, Janssen-Lozinska Y, Ulinski T. Effect of vitamin e coated dialyzers on anticoagulation requirement in hemodialyzed children. Saudi J Kidney Dis Transpl. 2010;21(3):466–70.
Islam MS, Hassan ZA, Chalmin F, Vido S, Berrada M, Verhelst D, et al. Vitamin e-coated and heparin-coated dialyzer membranes for heparin-free hemodialysis: a multicenter, randomized, crossover trial. Am J Kidney Dis. 2016;68(5):752–62.
Medrano C, Cointault O, Lavayssiere L, Nogier MB, Colliou E, Setbon N, et al. Heparin-free regional anticoagulation of haemodialysis filters with calcium-free dialysate: is citrate mandatory?Clin Kidney J. 2021;14(12):2534–8.
Fan Y, Wu F, Zou M, Gong Y, Hu Z, Jiang T, et al. An individualized regional citrate anticoagulation protocol for hemodialysis: a real-world retrospective study. Int Urol Nephrol. 2023.
Zhou Z, Liu C, Yang Y, Wang F, Zhang L, Fu P. Anticoagulation options for continuous renal replacement therapy in critically ill patients: a systematic review and network meta-analysis of randomized controlled trials. Crit Care. 2023;27(1):222.
Liu C, Mao Z, Kang H, Hu J, Zhou F. Regional citrate versus heparin anticoagulation for continuous renal replacement therapy in critically ill patients: a meta-analysis with trial sequential analysis of randomized controlled trials. Crit Care. 2016;20(1):144.
Brunot V, Serre JE, Mourad G, Klouche K, Pernin V. Heparin-free renal replacement therapy for chronic hemodialyzed patients at high risk for bleeding: a comparison of on-line predilution hemodiafiltration with conventional hemodialysis. Hemodial Int. 2018;22(4):463–73.
Krummel T, Cellot E, Thiery A, De Geyer G, Keller N, Hannedouche T. Hemodialysis without anticoagulation: less clotting in conventional hemodialysis than in predilution hemodiafiltration. Hemodial Int. 2019;23(4):426–32.
Hatanaka Y, Inoue S, Goto K, Yasuda N, Hidaka S, Kitano T. Vitamin e-coated polysulfone membrane-based hemodiafiltration attenuates inflammation in a rat model of lipopolysaccharide-induced systemic inflammation. Iran J Med Sci. 2017;42(5):465–72.
Himeno E, Goto S, Inoue S, Hatanaka Y, Hagiwara S, Matsumoto S, et al. Application and efficacy of vitamin e-bonded polysulfone membrane in acute blood purification therapy. Blood Purif. 2023;52(5):415–21.
Canaud B, Chenine L, Renaud S, Leray H. Optimal therapeutic conditions for online hemodiafiltration. Contrib Nephrol. 2011;168:28–38.
Susantitaphong P, Riella C, Jaber BL. Effect of ultrapure dialysate on markers of inflammation, oxidative stress, nutrition and anemia parameters: a meta-analysis. Nephrol Dial Transplant. 2013;28(2):438–46.
Di Iorio B, Di Micco L, Bruzzese D, Nardone L, Russo L, Formisano P, et al. Ultrapure dialysis water obtained with additional ultrafilter may reduce inflammation in patients on hemodialysis. J Nephrol. 2017;30(6):795–801.
García-Prieto A, de la Flor JC, Coll E, Iglesias E, Reque J, Valga F. Expanded hemodialysis: what’s up, doc?Clin Kidney J. 2023;16(7):1071–80.
Maduell F, Broseta JJ, Rodríguez-Espinosa D, Del Risco J, Rodas LM, Arias-Guillén M, et al. Comparison of four medium cut-off dialyzers. Clin Kidney J. 2022;15(12):2292–9.
Li AN, Li S, Zhang YJ, Xu XR, Chen YM, Li HB. Resources and biological activities of natural polyphenols. Nutrients. 2014;6(12):6020–47.
Rudrapal M, Khairnar SJ, Khan J, Dukhyil AB, Ansari MA, Alomary MN, et al. Dietary polyphenols and their role in oxidative stress-induced human diseases: insights into protective effects, antioxidant potentials and mechanism(s) of action. Front Pharmacol. 2022;13:806470.
Serino A, Salazar G. Protective role of polyphenols against vascular inflammation, aging and cardiovascular disease. Nutrients. 2018;11(1):53.
Yan ZM, Zhong YZ, Duan YH, Chen QH, Li FN. Antioxidant mechanism of tea polyphenols and its impact on health benefits. Anim Nutr. 2020;6(2):115–23.
Gulcin I, Huyut Z, Elmastas M, Aboul-Enein HY. Radical scavenging and antioxidant activity of tannic acid. Arab J Chem. 2010;3(1):43–53.
Baldwin A, Booth BW. Biomedical applications of tannic acid. J Biomater Appl. 2022;36(8):1503–23.
Kaczmarek B. Tannic acid with antiviral and antibacterial activity as a promising component of biomaterials — a minireview. Materials. 2020;13(14):3224.
Guo ZH, Xie WS, Lu JS, Guo XX, Xu JZ, Xu WL, et al. Tannic acid-based metal phenolic networks for bio-applications: a review. J Mater Chem B. 2021;9(20):4098–110.
Wei ZW, Fan ZY, Peng GG, Si HB, Yang L, Wang ZJ, et al. Extracorporeal hemoperfusion therapy for sepsis: multi-lamellar microspheres towards cascade endotoxin removal and broad-spectrum radical eliminating. Chem Eng J. 2022;444:136499.
Wei ZW, Peng GG, Zhao YQ, Chen SQ, Wang R, Mao H, et al. Engineering antioxidative cascade metal-phenolic nanozymes for alleviating oxidative stress during extracorporeal blood purification. ACS Nano. 2022;16(11):18329–43.
Zhang ZZ, Zhao YY, Luo X, Feng SM, Wu LL. Preparation of a heparin-like functionalized tannic acid-coated polyethersulfone ultrafiltration membrane for hemodialysis by a simple surface modification method. Appl Surf Sci. 2022;572:151440.
Chen Q, Kou MS, He Y, Zhao YP, Chen L. Constructing hierarchical surface structure of hemodialysis membranes to intervene in oxidative stress through Michael addition reaction between tannic acid and PEtOx brushes. J Memb Sci. 2022;657:120700.
Chen Q, He Y, Zhao YP, Chen L. Intervening oxidative stress integrated with an excellent biocompatibility of hemodialysis membrane fabricated by nucleobase-recognized co-immobilization strategy of tannic acid, looped PEtOx brush and heparin. J Memb Sci. 2021;625:119174.
Chen Q, He Y, Zhao YP, Chen L. Tannic acid and Poly(N-acryloyl morpholine) layer-by-layer built hemodialysis membrane surface for intervening oxidative stress integrated with high biocompatibility and dialysis performance. J Memb Sci. 2021;621:118896.
Chen SQ, Xie Y, Xiao TJ, Zhao WF, Li JS, Zhao CS. Tannic acid-inspiration and post-crosslinking of zwitterionic polymer as a universal approach towards antifouling surface. Chem Eng J. 2018;337:122–32.
Wei QY, Feng SM, Zhang ZZ, Liu LL, Wu LL. A high-protein retained PES hemodialysis membrane with tannic acid as a multifunctional modifier. Colloids Surf B Biointerfaces. 2022;220:112921.
Xu L, Ji H, Zhong R, Cheng S, Dang G, Xu T, et al. Antioxidative hydrogel-embedded polyethersulfone membrane with improved hemocompatibility to alleviate oxidative stress. J Memb Sci. 2023;684:121866.
Deng L, Qi YF, Liu ZH, Xi Y, Xue W. Effect of tannic acid on blood components and functions. Colloids Surf B Biointerfaces. 2019;184:110505.
Li CH, Wang Z, Lei H, Zhang D. Recent progress in nanotechnology-based drug carriers for resveratrol delivery. Drug Deliv. 2023;30(1):2174206.
Qi XC, Yang N, Luo Y, Jia XM, Zhao JQ, Feng X, et al. Resveratrol as a plant type antioxidant modifier for polysulfone membranes to improve hemodialysis-induced oxidative stress. Mater Sci Eng C Mater Biol Appl. 2021;123:111953.
Surai PF. Silymarin as a natural antioxidant: an overview of the current evidence and perspectives. Antioxidants. 2015;4(1):204–47.
Latacela GA, Ramaiah P, Patra I, Jalil AT, Gupta R, Madaminov FA, et al. The radioprotective potentials of silymarin/silibinin against radiotherapy-induced toxicities: a systematic review of clinical and experimental studies. Curr Med Chem. 2023;30(33):3775–97.
Meng D, Wang YL, Liu TJ. Protective effects of silibinin on LPS-induced inflammation in human periodontal ligament cells. Front Chem. 2022;10:1019663.
Li X, Zhou R, Han Y, Zeng J, Shi L, Mao Y, et al. Silibinin attenuates experimental periodontitis by downregulation of inflammation and oxidative stress. Oxid Med Cell Longev. 2023;2023:5617800.
Yang N, Jia XM, Wang DD, Wei CJ, He Y, Chen L, et al. Silibinin as a natural antioxidant for modifying polysulfone membranes to suppress hemodialysis-induced oxidative stress. J Memb Sci. 2019;574:86–99.
Salehi B, Berkay Yılmaz Y, Antika G, Boyunegmez Tumer T, Fawzi Mahomoodally M, Lobine D, et al. Insights on the use of α-lipoic acid for therapeutic purposes. Biomolecules. 2019;9(8):356.
Mahlicli FY, Altinkaya SA. Immobilization of alpha lipoic acid onto polysulfone membranes to suppress hemodialysis induced oxidative stress. J Memb Sci. 2014;449:27–37.
Abdel Hamid DZ, Nienaa YA, Mostafa TM. Alpha-lipoic acid improved anemia, erythropoietin resistance, maintained glycemic control, and reduced cardiovascular risk in diabetic patients on hemodialysis: a multi-center prospective randomized controlled study. Eur Rev Med Pharmacol Sci. 2022;26(7):2313–29.
Kohlova M, Rocha S, Gomes Amorim C, de Nova Araújo A, Santos-Silva A, Solich P, et al. Doping polysulfone membrane with alpha-tocopherol and alpha-lipoic acid for suppressing oxidative stress induced by hemodialysis treatment. Macromol Biosci. 2020;20(7):e2000046.
Wei QY, Feng SM, Wu LL. Glomerular endothelium-inspired anticoagulant surface coating on polyethersulfone hemodialysis membrane. Mater Chem Phys. 2023;297:127364.
Haghighat N, Shimi G, Shiraseb F, Karbasi A, Nadery M, Ashtary-larky D, et al. The effects of conjugated linoleic acid supplementation on liver function enzymes and malondialdehyde in adults: a GRADE-assessed systematic review and dose-response meta-analysis. Pharmacol Res. 2022;186:106518.
Kung FC, Yang MC. The effect of covalently bonded conjugated linoleic acid on the reduction of oxidative stress and blood coagulation for polysulfone hemodialyzer membrane. Int J Biol Macromol. 2006;38(3–5):157–64.
Tran NMP, Huynh TLD, Phan BN, Dang NNT, Phan TB, Ha HTT, et al. Conjugated linoleic acid grafting improved hemocompatibility of the polycaprolactone electrospun membrane. Int J Polym Sci. 2020;2020:1–8.
Kung FC, Yang MC. Effect of conjugated linoleic acid immobilization on the hemocompatibility of cellulose acetate membrane. Colloids Surf B Biointerfaces. 2006;47(1):36–42.
Kung FC, Yang MC. Effect of conjugated linoleic acid grafting on the hemocompatibility of polyacrylonitrile membrane. Polym Adv Technol. 2006;17(6):419–25.
Yasar Mahlicli F, Sen Y, Mutlu M, Alsoy Altinkaya S. Immobilization of superoxide dismutase/catalase onto polysulfone membranes to suppress hemodialysis-induced oxidative stress: a comparison of two immobilization methods. J Memb Sci. 2015;479:175–89.
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