Эффект диализатора с витамином Е на лечение анемии и уровень воспаления


Е.В. Шутов, О.В. Балкарова, Г.В. Котлярова

1 ГБУЗ «Городская клиническая больница им. С.П. Боткина ДЗМ»; Москва, Россия; 2 ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» МЗ РФ; Москва, Россия; 3 ГБУЗ «Городская клиническая больница № 24 ДЗМ»; Москва, Россия
Цель исследования. Несмотря на успехи гемодиализной терапии, одной из нерешенных остается проблема биосовместимости диализных мембран, которая приводит к ухудшению результатов лечения, а также способствует развитию резистентности к эритропоэтин-стимулирующим препаратам при лечении анемии.
Материал и методы. В открытое проспективное исследование по изучению влияния диализных мембран, покрытых витамином Е, на уровень воспаления и индекс резистентности к эритропоэтин-стимулирующим препаратам (ИРЭ) в течение 3 месяцев были включены 30 пациентов, получавших гемодиализ не менее 3 месяцев. Определялись ежемесячно: уровень интерлейкина-6 (ИЛ-6), С-реактивного белка, показатели обмена железа, альбумин, преальбумин.
Результаты. За время лечения больных с применением полисульфоновых диализных мембран, покрытых витамином Е, статистически значимо снизился уровень ИЛ-6 – с 9,4±13,5 до 1,3±2,1 пг/мл (p<0,001). Показатели обмена железа, альбумина, преальбумина и С-реактивного белка достоверно не изменились. ИРЭ в целом по группе достоверно не изменился, однако у пациентов с исходно высоким ИРЭ он снизился с 12,5±2,2 до 10,7±1,2 МЕ/кг/нед/г (р<0,05).
Выводы. Применение полисульфоновых диализных мембран, покрытых витамином Е, целесообразно использовать больным с высоким ИРЭ для лечения анемии и снижения уровня воспаления.

Литература


  1. Libetta C., Sepe V., Esposito P., Galli F., Dal Canton A. Oxidative stress and inflammation: implications in uremia and hemodialysis. Clin. Biochem. 2011;44:1189–1198. Doi: 10.1016/j.clinbiochem.2011.06.988.
  2. Mares J., Richtrova P., Hricinova A., Tuma Z., Moravec J., Lysak D., Matejovic M. Proteomic profiling of blood-dialyzer interactome reveals involvement of lectin complement pathway in hemodialysis-induced inflammatory response. Proteomics Clin. Appl. 2011;4:829–838. Doi: 10.1002/prca.201000031.
  3. Brunini T.M., Mendes-Ribeiro A.C., Ellory J.C., Mann G.E. Platelet nitric oxide synthesis in uremia and malnutrition: a role for L-arginine supplementation in vascular protection? Cardiovasc. Res. 2007;73:359–367. Doi: 10.1016/j.cardiores.2006.09.019.
  4. Libetta C., Sepe V., Esposito P., Galli F. Oxidative stress and inflammation: implications in uremia and hemodialysis. Clin. Biochem. 2011;44:1189–1198.
  5. Stoya G., Klemm A., Baumann E., Vogelsang H., Ott U., Linss W., Stein G. Determination of autofluorescence of red blood cells in uremic patients as a marker of oxidative damage. Clin. Nephrol. 2002;58:198–204.
  6. Elliott J., Mishler D., Agarwal R. Hyporesponsiveness to erythropoietin: causes and management. Adv. Chronic. Kidney Dis. 2009;16:94–100. Doi: 10.1053/j.ackd.2008.12.004.
  7. Locatelli F., Del Vecchio L., Pozzoni P., Andrulli S. Dialysis adequacy and response to erythropoiesis-stimulating agents: what is the evidence base? Semin. Nephrol. 2006;26:269–274. Doi: 10.1016/j.semnephrol.2006.05.002.
  8. Van der Steen A. Research on dialyzers with improved biocompatibility. Clin. Nephrol. 1986;26(1):S39–S42.
  9. Rousseau Y., Carreno M.P., Poignet J.L., Kazatchkine M.D., Haeffner-Cavaillon N. Dissociation between complement activation, integrin expression and neutropenia during hemodialysis. Biomaterials. 1999;20:1959–1967.
  10. Del Vecchio L., Locatelli F., Carini M. What we know about oxidative stress in patients with chronic kidney disease on dialysis – clinical effects, potential treatment, and prevention. Semin. Dial. 2011;24:56–64. Doi: 10.1111/j.1525-139X.2010.00819.x
  11. Ferraro B., Galli F., Frei B., Kingdon E., Canestrari F., Rice-Evans C., Buoncristiani U., Davenport A., Moore K.P. Peroxynitrite-induced oxidation of plasma lipids is enhanced in stable hemodialysis patients. Kidney Int. 2003;63:2207–2213. Doi: 10.1046/j.1523-1755.2003.00008.x
  12. Muller C., Eisenbrand G., Gradinger M., Rath T., Albert F.W., Vienken J., Singh R., Farmer P.B., Stockis J.P., Janzowski C. Effects of hemodialysis, dialyser type and iron infusion on oxidative stress in uremic patients. Free Radic. Res. 2004;38:1093–1100. Doi: 10.1080/10715760400011452.
  13. Ikizler T.A., Morrow J.D., Roberts L.J., Evanson J.A., Becker B., Hakim R.M., Shyr Y., Himmelfarb J. Plasma F2-isoprostane levels are elevated in chronic hemodialysis patients. Clin. Nephrol. 2002;58:190–197.
  14. Galli F., Benedetti S. Floridi A., Canestrari F., Piroddi M., Buoncristiani E., Buoncristiani U. Glycoxidation and inflammatory markers in patients on treatment with PMMA-based protein-leaking dialyzers. Kidney Int. 2005;67:750–759. Doi: 10.1111/j.1523-1755.2005.67138.x.
  15. Piroddi M., Palmese A., Pilolli F., Amoresano A., Pucci P., Ronco C., Galli F. Plasma nitroproteome of kidney disease patients. Amino Acids. 2011;40:653–667. Doi: 10.1007/s00726-010-0693-1.
  16. Thornalley P.J., Rabbani N. Protein damage in diabetes and uremia – identifying hotspots of proteome damage where minimal modification is amplified to marked pathophysiological effect. Free Radic. Res. 2011;45:89–100. Doi: 10.3109/10715762.2010.534162.
  17. Vanholder R., Baurmeister U., Brunet P., Cohen G., Glorieux G., Jankowski J. A bench to bedside view of uremic toxins. J. Am. Soc. Nephrol. 2008;19:863–870. Doi: 10.1681/ASN.2007121377.
  18. Vanholder R., Schepers E., Meert N., Lameire N. What is uremia? Retention versus oxidation. Blood Purif. 2006;24:33–38. Doi: 10.1159/000089434.
  19. De Smet R., Dhondt A., Eloot S., Galli F., Waterloos M.A., Vanholder R. Effect of the super-flux cellulose triacetate dialyser membrane on the removal of non-protein-bound and protein-bound uraemic solutes. Nephrol. Dial. Transplant. 2007;22:2006–2012. Doi: 10.1093/ndt/gfm065.
  20. Thomas G., Jaber B.L. Convective therapies for removal of middle molecular weight uremic toxins in end-stage renal disease: a review of the evidence. Semin. Dial. 2009;22:610–614. Doi: 10.1111/j.1525-139X.2009.00665.x.
  21. Galli F., Piroddi M., Annetti C., Aisa C., Floridi E., Floridi A.: Oxidative stress and reactive oxygen species. Contrib. Nephrol. 2005;149:240–260. Doi: 10.1159/000085686.
  22. Canestrari F., Galli F., Giorgini A., Albertini M.C., Galiotta P., Pascucci M., Bossu M. Erythrocyte redox state in uremic anemia: effects of hemodialysis and relevance of glutathione metabolism. Acta. Haematol. 1994;91:187–193. Doi: 10.1159/000204332.
  23. Boaz M., Smetana S., Weinstein T., Matas Z., Gafter U., Iaina A., Knecht A., Weissgarten Y., Brunner D., Fainaru M., Green M.S. Secondary prevention with antioxidants of cardiovascular disease in end-stage renal disease (SPACE): randomised placebo-controlled trial. Lancet. 2000;356:1213–1218.
  24. Clermont G., Lecour S., Cabanne J.F., Motte G., Guilland J.C., Chevet D., Rochette L.: Vitamin E-coated dialyzer reduces oxidative stress in hemodialysis patients. Free Radic. Biol. Med 2001;31:233–241.
  25. Sosa M.A., Balk E.M., Lau J., Liangos O., Balakrishnan V.S., Madias N.E., Pereira B.J., Jaber B.L. A systematic review of the effect of the Excebrane dialyser on biomarkers of lipid peroxidation. Nephrol. Dial. Transplant. 2006;21:2825–2833. Doi: 10.1093/ndt/gfl376.
  26. Usberti M., Gerardi G., Bufano G., Tira P., Micheli A., Albertini A., Floridi A., Di Lorenzo D., Galli F. Effects of erythropoietin and vitamin E-modified membrane on plasma oxidative stress markers and anemia of hemodialyzed patients. Am. J. Kidney Dis. 2002;40:590–599. Doi: 10.1053/ajkd.2002.34919.
  27. Kobayashi S., Moriya H., Aso K., Ohtake T. Vitamin E-bonded hemodialyzer improves atherosclerosis associated with a rheological improvement of circulating red blood cells. Kidney Int. 2003;63:1881–1887. Doi: 10.1046/j.1523-1755.2003.00920.x.
  28. Nakatan T., Takemoto Y., Tsuchida A.K. The effect of vitamin E-bonded dialyzer membrane on red blood cell survival in hemodialyzed patients. Artif. Organs. 2003;27:214–217.
  29. Cruz D.N., De Cal M., Garzotto F., Brendolan A., Nalesso D., Corradi V., Ronco C. Effect of vitamin E-coated dialysis membranes on anemia in patients with chronic kidney disease: an Italian multicenter study. Int. J. Artif. Organs. 2008;31:545–552.
  30. Cruz D.N., de Cal M., Ronco C. Oxidative stress and anemia in chronic hemodialysis: the promise of bioreactive membranes. Contrib. Nephrol. 2008;161:89–98. Doi: 10.1159/000130413 .
  31. Tarng D.C., Huang T.P., Liu T.Y., Chen H.W., Sung Y.J., Wei Y.H. Effect of vitamin E-bonded membrane on the 8-hydroxy-2′-deoxyguanosine level in leukocyte DNA of hemodialysis patients. Kidney Int. 2000;58:790–799. Doi: 10.1046/j.1523-1755.2000.00228.x.
  32. Miyazaki H., Matsuoka H., Itabe H., Usui M., Ueda S., Okuda S., Imaizumi T. Hemodialysis impairs endothelial function via oxidative stress: effects of vitamin E-coated dialyzer. Circulation 2000;101:1002–1006.
  33. Clermont G., Lecour S., Cabanne J.F., Motte G., Guilland J.C., Chevet D., Rochette L. Vitamin E-coated dialyzer reduces oxidative stress in hemodialysis patients. Free Radic. Biol. Med. 2001;31:233–241.
  34. Westhuyzen J., Saltissi D., Stanbury V. Oxidative stress and erythrocyte integrity in end-stage renal failure patients hemodialysed using a vitamin E-modified membrane. Ann. Clin. Lab. Sci. 2003;33:3–10.
  35. Bufano G., Usberti M., Mandolfo S., Malberti F., Piroddi M., Galli F. Von Willebrand factor and autoantibodies against oxidized LDL in hemodialysis patients treated with vitamin E-modified dialyzers. Int. J. Artif. Organs. 2004;27:214–221.
  36. Mydlik M., Derzsiova K., Racz O., Sipulova A., Lovasova E., Molcanyiova A., Petrovicova J. Vitamin E-coated dialyzer and antioxidant defense parameters: a three-month study. Semin. Nephrol. 2004;24:525–531.
  37. Calò L.A, Naso A., Pagnin E., Davis P.A., Castoro M., Corradin R., Riegler P., Cascone C., Huber W., Piccoli A. Vitamin E-coated dialyzers reduce oxidative stress-related proteins and markers in hemodialysis – a molecular biological approach. Clin. Nephrol. 2004;62:355–361.
  38. Odetti P., Traverso N., Monacelli F., Menini S., Vazzana J., Tasso B., Pronzato M.A., Robaudo C., Deferrari G. Vitamin E-coated filter decreases levels of free 4-hydroxyl-2-nonenal during haemodialysis sessions. Free Radic. Res. 2006;40:207–212. Doi: 10.1080/10715760500445121.
  39. Washio K., Inagaki M., Tsuji M., Morio Y., Gotoh H., Gotoh Y., Oguchi K. Correlation between leukocyte membrane lipid peroxidation and expression of Cu/Zn superoxide dismutase MRNA in hemodialysis patients. Blood. Purif. 2011;33:59–65. Doi: 10.1159/000333840.
  40. Akiyama S., Inagaki M., Tsuji M., Gotoh H., Gotoh T., Washio K., Gotoh Y., Oguchi K. Comparison of effect of vitamin E-coated dialyzer and oral vitamin E on hemodialysis-induced Cu/Zn superoxide dismutase. Am. J. Nephrol. 2005;25:500–506. Doi: 10.1159/000088172.
  41. Omata M., Higuchi C., Demura R., Sanaka T., Nihei H. Reduction of neutrophil activation by vitamin E-modified dialyzer membranes. Nephron. 2000;85:221–231. Doi: 10.1159/000045665.
  42. Betjes M.G., Hoekstra F.M., Klepper M., Postma S.M., Vaessen L.M. Vitamin E-coated dialyzer membranes downregulate expression of monocyte adhesion and co-stimulatory molecules. Blood. Purif. 2004;22:510–517. Doi: 10.1159/000082042.
  43. Zaluska W.T., Ksiazek A., Roliski J. Effect of vitamin E-modified cellulose membrane on human lymphocyte, monocyte, and granulocyte CD11b/CD18 adhesion molecule expression during hemodialysis. ASAIO. J. 2001;47:619–622.
  44. Pertosa G., Grandaliano G., Soccio M., Martino C., Gesualdo L., Schena F.P. Vitamin E-modified filters modulate Jun N-terminal kinase activation in peripheral blood mononuclear cells. Kidney Int. 2002;62:602–610. Doi: 10.1046/j.1523-1755.2002.00458.x.
  45. Tsuruoka S., Kawaguchi A., Nishiki K., Hayasaka T., Fukushima C., Sugimoto K., Saito T., Fujimura A. Vitamin E-bonded hemodialyzer improves neutrophil function and oxidative stress in patients with end-stage renal failure. Am. J. Kidney Dis. 2002;39:127–133. Doi: 10.1053/ajkd.2002.29901.
  46. Libetta C., Zucchi M., Gori E., Sepe V., Galli F., Meloni F., Milanesi F., Dal Canton A. Vitamin E-loaded dialyzer resets PBMC-operated cytokine network in dialysis patients. Kidney Int. 2004;65:1473–1481. Doi: 10.1111/j.1523-1755.2004.00528.x.
  47. Kojima K., Oda K., Homma H., Takahashi K., Kanda Y., Inokami T., Uchida S. Effect of vitamin E-bonded dialyzer on eosinophilia in haemodialysis patients. Nephrol. Dial. Transplant. 2005;20:1932–1935. Doi: 10.1093/ndt/gfh912.
  48. 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;20:364–368.
  49. Yoshida K., Kitauchi T., Kimura S., Yoneda T., Uemura H., Ozono S., Hirao Y. Serum neopterin monitoring and vitamin E-modified, regenerated hemodialyzer membrane influence on biocompatibility. Artif. Organs. 2002;26:54–57.
  50. Baragetti I., Furiani S., Vettoretti S., Raselli S., Maggi F.M., Galli F., Catapano A.L., Buccianti G. Role of vitamin E-coated membrane in reducing advanced glycation end products in hemodialysis patients: a pilot study. Blood. Purif. 2006;24:369–376. Doi: 10.1159/000093678.
  51. Kirmizis D., Papagianni A., Belechri A.M., 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;26:2296–2301. Doi: 10.1093/ndt/gfq715.
  52. Takouli L., Hadjiyannakos D., Metaxaki P., Sideris V., Filiopoulos V., Anogiati A., Vlassopoulos D. Vitamin E-coated cellulose acetate dialysis membrane: long-term effect on inflammation and oxidative stress. Ren. Fail. 2010;32:287–293. Doi: 10.3109/08860221003615795.
  53. Andrulli S., Di Filippo S., Manzoni C., Stefanelli L., Floridi A., Galli F., Locatelli F. Effect of synthetic vitamin E-bonded membrane on responsiveness to erythropoiesis-stimulating agents in hemodialysis patients: a pilot study. Nephron. Clin. Pract. 2010;115:C82–C89. Doi: 10.1159/000294281.
  54. Panichi V., Rosati A., Paoletti S., Ferrandello P., Migliori M., Beati S., Bernabini G., Daini R., Casani A., Angelini D., Parrini M., Rossi A., Petrone I., Barsotti G. 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;32:7–14. Doi: 10.1159/000321369.
  55. Simon W.L., Angela M. Carter, Emma J. Dunn et. al. 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):649–656.
  56. Sanaka T., Mochizuki T., Kinugasa E. Ohwada S., Kuno T., Kojima K., Kobayashi S., Satoh M., Shimada N., Nakao K., Nakazawa R., Nishimura H., Noiri E., Shigematsu T., Tomo T., Maeda T. Randomized controlled open-label trial of vitamin E-bonded polysulfone dialyzer and erythropoiesis-stimulating agent response. Clin. J. Am. Soc. Nephrol. 2013;8(6):969–978. Doi: 10.2215/CJN.04680512.
  57. D’Arrigo G.A., Baggetta R.A., Tripepi G.A., Galli F.B., Bolignano D. Effects of vitamin E-coated versus conventional membranes in chronic hemodialysis patients: a systematic review and meta-Analysis. Blood. Purif. 2017;43:101–122. Doi: 10.1159/000453444.


Об авторах / Для корреспонденции


Шутов Е.В. – д.м.н., зав. отделением нефрологии № 12 ГБУЗ «ГКБ им. С.П. Боткина ДЗМ» , профессор кафедры нефрологии и гемодиализа ФГБОУ ДПО РМАПО; Москва, Россия. E-mail: shutov_e_v@mail.ru
Балкарова О.В. – зав. отделением гемодиализа ГБУЗ «ГКБ № 24 ДЗМ»; Москва, Россия.
Котлярова Г.В. – к.м.н., врач-нефролог ГБУЗ «ГКБ им. С.П. Боткина ДЗМ»; Москва, Россия.


Похожие статьи


Бионика Медиа