<< Вернуться к списку статей журнала

Том 2 №3 2000 год - Нефрология и диализ

Роль мофетила микофенолата в арсенале современных иммуносупрессивных препаратов

Корсакова Т.В.

Аннотация: С тех пор как для иммуносупрессии были внедрены такие препараты, как циклоспорин А (СуА) и такролимус (FK 506), аллотрансплантация почки стала методом выбора для большинства больных с терминальной почечной недостаточностью. Это определяется тем, что в сравнении с традиционными преднизолоном и азатиопорином (Аза) CyA и FK 506 обладают более высокой иммунодепрессивной активностью при снижении опасности тяжелых, подчас фатальных побочных эффектов. Как следствие, широкое внедрение их в клиническую трансплантологию способствовало увеличению выживаемости больных и увеличению доли функционирующих трансплантатов. Однако будучи высокоэффективными иммуносупрессантами [31, 44], эти препараты вызывают ряд серьезных токсических побочных эффектов [26]. Так, в настоящее время хорошо известна нефротоксичность СуА [5, 54], которая проявляется снижением скорости клубочковой фильтрации, канальцевым ацидозом и гиперурикемией [5, 11, 54]. Описаны и характерные морфологические признаки этого нефротоксического эффекта [46, 54]. Более того, показано, что в отдаленной перспективе хроническое нефротоксическое действие CyA может способствовать развитию хронической недостаточности трансплантата.

Для цитирования: Корсакова Т.В. Роль мофетила микофенолата в арсенале современных иммуносупрессивных препаратов. Нефрология и диализ. 2000. 2(3):171-176. doi:

Весь текст

Ключевые слова: селлсепт, трансплантация почки, кризы отторжения, хроническое отторжение

Список литературы:

1. Арутюнян С.М. Ультразвуковая диагностика отторжения пересаженной почки в ближайшем послеоперационном периоде. Дис. … канд. мед. наук. М., 1994; 200.
2. Баранова Ф.С., Мойсюк Я.Г. Иммунология в клинической аллотрансплантации органов. Иммунодепрессия. Трансплантология. Руководство под редакцией В.И Шумакова. М., Медицина 1995; 62-71.
3. Белорусов О.С., Горяйнов В.А., Синютин А.А. Причины потерь аллогенных почек в раннем посттрансплантационном периоде. Трансплантология и искусственные органы. 1998; 4: 27.
4. Abouna G.M. et al. Mycophenolate mofetil immunosupression in high risk renal transplant recipients. 3rd International conference on new trends in clinical and experimental immunosuppression. Geneva. 1998; [Abstract]. 62.
5. Ader L.G., Tack I. et al. Renal functional reverse cyclosporine-treater recipients of kidney transplant. Kidney Int. - 1994; Vol. 46. 1657.
6. Allison A.C., Eugui E.M. Mycophenolate mofetil, a rationally designed immunosuppressive drug. Clin Transpl. 1993; Vol. 7; 96-112.
7. Allison A.C., Eugui E.M. Immunosuppressive and other effects of mycophenolic acid and an ester prodrug, mycophenolate mofetil. Immunol Rev. 1993; Vol. 136; 1.
8. Almond P.S., Matas A., Gillingham K. et al. Risk factors for chronic rejection in renal allograft recipients. Transplantation. 1993; Vol. 55; 752-7.
9. Alonso A. et al. Mycophenolate Mofetil in the prevention of renal allograft rejection: a single center experience. The International Congress on Immunosuppression. Orlando. 1997; [Abstract 94]. 162.
10. Behrend M. et al. Triple immunosupression with mycophenolate mofetil, neoral and steroids: experience in 185 consecutive kidney transplant recipients. The International Congress on Immunosuppression. Orlando. 1997; [Abstract 104]. 164.
11. Bertani T. Nature and extent of glomerular injury induced by cyclosporine in heart transplant recipients. Kidney Int. 1991; Vol. 40; 243.
12. Budde K. et al. Steroid Withdrawal During the First Year after Renal Transplantation in Cyclosporine and Mycophenolate Mofetil Treated Patients. 9th Congress of the European Society for Organ Transplantation. Oslo. 1999; [Abstract 1087].
13. Budde K. et al. Steroid Withdrawal in Long-Term Cyclosporine Treated Patients Using Mycophenolate Mofetil: A Prospective Randomised Pilot Study 9th Congress of the European Society for Organ Transplantation. Oslo. 1999; [Abstract 1088].
14. Cecka J.M., Terrasaki P.I. Early rejection episodes In: Terrasaki P.I.ed. Clinical Transplants 1989. Los Angeles :UCLA Tissue Laboratory. 1989; 425-434.
15. Chan G.L.C., Canatfax D.M., Johnson C.A. The therapeutic use of azathioprine in renal transplantation. Pharmacotherapy. 1987; Vol. 7; 165-77.
16. Eggers P.W. Comparison of treatment costs between dialysis and transplantation. Semin Nephrol. 1992; Vol. 12; 284-292.
17. Esineraldo R.M. et al. Mycophenolate Mofetil with Lower Cyclosporine Dose in High-Risk Renal Transplant Recipients. 9th Congress of the European Society for Organ Transplantation. Oslo. 1999; [Abstract 1155].
18. Eugui E.M., Almquist S.J., Muller C.D., Allison A.C. Lymphocytoselective citostatic and immunosuppressive effects of mycophenolic acid in vitro: role of deoxyguanosine nucleotide depletion. Scand J Immunol. 1991; Vol. 33; 175.
19. Eugui E.M., Mirkovich A., Allison A.C. Limphocyte-selective antiproliferative and immunosupressive effects of mycophenolic acid in mice. Scand J Immunol. 1991; Vol. 33; 175.
20. European Mycophenolate Mofetil Cooperative Study Group. Placebo-controlled Study of Mycophenolate Mofetil combinated with cyclosporin and corticosteroids for prevention of acute rejection. Lancet. 1995; Vol. 345; 1321-5.
21. Ferguson R. Acute rejection episodes. Best predictor of long-term primary cadaveric renal transplant survival. Сlin Transplant. 1994; Vol. 8; 328.
22. Francon G. et al. Woodle E.S. et al. Mycophenolate Mofetil (MMF) and reduction in cyclosporine (СуА) dosage for chronic renal allograft reection - 1 year result. New Demensions in Transplantation. Florence. 1998; [Abstract]. 279.
23. Garmellini M. et al. Mycophenolate Mofetil (Neoral) Steroid vs Neoral (Steroid) therathy for Prophylaxis of Acute Rejection in Renal Transplant recipients. Transplantation Proceeding. 1999; Vol. 31; 1162-1164.
24. Goldblum R. Therapy of rheumatoid arthritis with mycophenolate mofetil. Clin. Exp. Rheumatol. 1993; Vol. 11; 117-119.
25. Goldsmith M.P. Researchers follow varied molecular paths towards better control of organ rejection [news]. JAMA. 1990; Vol. 263; 1184-1187.
26. Goldstein D.J., Zuech N., Sengal V. et al. Cyclosporine-assosiated end-stage nephropathy after cardiac transplantation. Transplantation. 1997; Vol. 64; 664.
27. Gulanikar A.C., MacDonald A.C., Sungurtekin U., Belitsky P. The incidence and impact of early rejection episodes on graft outcome in recipients of first cadaver kidney transplants. Transplantation. 1992; Vol. 53; 323.
28. Hall B.M., Tiller D.J. Comparison of three immunosuppressive regimen in cadaver renal transplantation: Long-term cyclosporine, short-term cyclosporine followed by azathioprine and prednisolone, and azathioprine and prednisolone without cyclosporine. N Engl J Med. 1988; Vol. 318; 1499.
29. Halloran P. Mycophenolate Mofetil in renal allograft recipients. Apooled Efficacy Analysis of Three randomised, double-blind clinical studies in prevention of rejection. Transplantation. 1997; Vol. 63; 39-47.
30. Handschumacher R.E. Immunosuppressive agents. In: Gilman A.G., Rail T.W., Nies A.S. et al. editors. Goodman & Gilman’s the pharmacological basis of therapeutics, 8th ed. v. 2. New York: McGraw-Hill, Inc. 1992; 1264-76;
31. Heldermann J.H. et al. New Immunologically Non-Specific Immunosupressive Agents Dictate Changes in Standard Protocols for Renal Transplant Management. Nephrol. Dial. Transplant. 1997; Vol. 12; 51-54.
32. Hoffmann-La Roche Inc. Mycophenolate mofetil prescribing information. Nutley (NJ). 1995.
33. Hollander A.M.J. et al. Beneficial effects of conversion from cyclosporin to azathioprine after kidney transplantation. Lancet. 1995; Vol. 345; 610.
34. Joser M. Grinyo et al. Steroid withdrawal in mycophenalate mofetil-treated renal allograft recipients. Transplantation. 1997; Vol. 63; 1688-1690.
35. Kaminska B. et al. Randomised Open Clinical Trial of Conversion from Mycophenolate Mofetil to Azathioprine in Cadaveric Renal Transplantation. 9th Congress of the European Society for Organ Transplantation. Oslo. 1999. [Abstract 1158].
36. Keuneke Ch. et al. Successful conversion in long-term allograft recipients to Mycophenolate Mofetil (MMF) monotherapy - an example of future optimal maintenance treatment? 9th Congress of the European Society for Organ Transplantation. Oslo. 1999; [Abstract 1086].
37. Kliem V. et al. Mycophenolate Mofetil in Chronic Renal Graft Dysfunction. 9th Congress of the European Society for Organ Transplantation. Oslo. 1999. [Abstract 1157].
38. Kliem V. et al. Treatment of Chronic Renal Allograft Failure by Addition of Mycophenolate Mofetil: Single-Center Experience in 40 Patients. Transplantation Proceeding. 1999; Vol. 31; 272-273.
39. Koyma H., Cecka J.M. Rejection episodes. Clin Transpl. 1992; 331.
40. Langman L.J., LeGatt D.F., Yatscoff R.W. Blood distribution of mycophenolic acid. Ther. Drag. Monit. 1994; Vol. 16; 602-7.
41. Lee H.J., Pawlak K., Nguyen B.T. et al. Biochemical differences among four inosinate dehydrogenase inhibitors, mycophenolic acid, ribavirin, tiazofurin and selenazofurin, studied in mouse lymphomacell culture. Cancer Res. 1985; Vol. 45; 5512-20.
42. Lee W.A., Gu L., Miksztal A.R. et al. Bioavailabilily improvement of mycophenolic acid through amino ester derivatisation. Pharm Res. 1992; Vol. 12; 97-9.
43. Lee W.A., Gu L., Miksztal A.R., Сhu N., Leung K., Nelson P.H. Bioavailability improvement of mycophenolic acid through amino ester derivatisation. Pharm Res 1990; 7: 161.
44. Mason J. The pathophysiology of Sandimmune (cyclosporine) in man and animals. Pediatr Nephol. 1990; Vol. 4; 554.
45. Meyer C. et al. Clinical experience with Mycophenolate Mofetil (MMF) in chronic allograft dysfunction. 9th Congress of the European Society for Organ Transplantation. Oslo. 1999; [Abstract 1023].
46. Mihatsch M.J. Morfologic diagnosis of cyclosporine nephrotoxicity. Semin Diagn Pathol. 1988; Vol. 5; 104.
47. Miller J., for the FK 506 Dose Ranging Kidney Transplant Study Group. Tacrolimus and Mycophenolate Mofetil in Renal Transplant Recipients: One Year Results of a Multicenter, Randomized Doze Ranging Trial. Transplantation Proceeding. 1999; Vol. 31; 276-277.
48. Morris R.E., Hoyt E.G., Murphy M.P. et al. Mycophenolic acid morpholinoethylester (RS-61443) is a new immunosuppressant that prevents and halts heart allograft rejection by selective inhibition of T- and B-cell purine synthesis. Transplant I Proc. 1990; Vol. 22; 1659-62.
49. Morris R.E., Wang J. Comparison of the immunosuppressive effects of mycophenolic acid and the morpholinoethyl ester of mycophenolic acid (RS-61443) in recipients of heart allografts. Transplant Proc. 1991; Vol. 23; 493-6.
50. Morris R.E. Immunopharmacology of new xenobiotic immunosuppressive molecules. Semin Nephrol. 1992; Vol.12; 304-14.
51. Morris R.E. New small molecule immunosuppressants for transplantation: review of essential concepts. J Heart Lung Transplant. 1993; Vol. 12; 275-86.
52. Morris R.E., Wang J., Blum J.R. et al. Immunosuppressive effects in rat and nonhuman primate recipients of heart allografts. Transplantat Proc. 1991; 23 (suppe).; 19.
53. Morris-Stiff G., Jurewiez W.A. Single centre experience with mycophenolate mofetil for refractory rejection in cadaveric renal transplantation. Transpl Int. 1998; Vol. 1; 204-207.
54. Myers B.D., Ross J. et al. Cyclosporin-associated chronic nephropathy. N Engl Med. 1984; Vol. 311; 699.
55. Neylan J., Chos et al. The US Mycophenalate Mofetil Prevention of Rejection Study in Cadaveric Renal Transplantation: a 3-year follow-up. [Abstract 344]. 215.
56. Pescovitz M.D. Mycophenolate Mofetil for the Treatment of First Renal Allograft Rejection. Transplantation. 1998; Vol. 65; 235-241.
57. Pescovitz M.D. et al. Mycophenolate Mofetil for the Treatment of First Acute Renal Allograft Rejection. [Abstract 113]. 74.
58. Picklmayr R., Vanrenterghem Y. et al. European Mycophenolate Mofetil trial: 3-year results. [Abstract 112].
59. Rizzo G. et al. Evaluation in Efficacy of Mycophenolate Mofetil (MMF) for Prophilaxis of Rejection in Renal Transplant Recipients: Comparison Between Double Theraphy with Sundimmun Neoral (SN) and Steroids (S) and Triple Theraphy with Azathoprine (AZA). 9th Congress of the European Society for Organ Transplantation. Oslo. 1999; [Abstract 1022].
60. Senn B., Rochat P. et al. Mycophenolate Mofetil in ongoing chronic kidney allograft dysfunction. 3rd International conference on new trends in clinical and experimental immunosuppression. Geneva. 1998; [Abstract]. 126.
61. Sevaux R.G.L. et al. MMF allows low-doser cyclosporine in renal transplant recipients. 17th Annual Meeting of the American Society of Transplant Physicians (ASTP). Chicago. 1998; [Abstract]. 10.
62. Shah J., Kauffman R., Sollinger H. et al. Pharmacokinetics of MPA in renal transplant patients. Pharm Res. 1991; 8 (suppl). S. 310. [Abstract].
63. Sharma V.K., Li B., Khanna A. et al. Which way for drug-mediated immunosuppression? Curr Opin Immunol. 1994; Vol. 6. 784-90.
64. Sheldon T. Problems of using in the economic evaluation of health care. Health Econ. 1996; Vol. 5. 1.
65. Sollinger H.W., Deierhoi M.H., Belzer F.O. et al. RS-61443 - a phase I clinical trial and pilot rescue study. Transplantation. 1992; Vol. 53. 428-32.
66. Sollinger H.W. for the US. Renal Transplant Mycophenolate Mofetil Study Group. Mycophenolate Mofetil for the prevention of acute rejection in primary cadaveric renal recipients. Transplantation. 1995; Vol. 60. 225-32.
67. Sullivan S.D., Garrison L.P., Best. Экономическая эффективность мофетила микофенолата в первый год после первичной пересадки трупной почки. J Am Soc Nephrol. 1997; Vol. 8. 1592-1598.
68. Sollinger H.W., Belzer F.O. et al. RS-61443: rescue therapy in refractory kidney transplant rejection. Transplant Proc. 1993; Vol. 25. 698-699.
69. Sutherland F., Burgess E. Posttransplant conversion from cyclosporin to azathioprine: effect on cardiovascular risk profile. Transpl Int 1993; Vol. 6. 129.
70. The Mycophenolate Mofetil Renal Refractory Rejection Rtudu Group. Mycophenolate Mofetil for the treatment of refractory acute cellular renal transplant rejection. Transplantation 1996; Vol. 61. 722-2.
71. The Tricontinental Mycophenolate Mofetil Renal Transplantation Study Group. A blinde, randomized clinical trial of mycophenolate mofetil for the prevention of acute rejection in cadaveric renal transplantation. Transplantation. 1996; Vol. 61; 1029-37. mycophenolic acid. Ther Drug Monit. 1994; 16; 602-7.
72. Tousignant P., Guttman R.D., Hollomby D.J. Transplantation and home hemodialysis. Their cost-effectiveness. J Chronic Dis. 1985; Vol. 38. 589-601.
73. US Department of Health and Human Services. End Stage Renal Disease Research Report 1993-1995. Baltimore. MD. Health Care Financing Administration. 1997; in press.
74. Vanrenterghem Y.F.C. A Randomized double-blind, multi-center trial comparing two corticosteroid regimens in combination with mycophenolate mofetil (MMF) and cyclosporine (СуА) in cadaveric renal transplant recipients. 3rd International conference on new trends in clinical and experimental immunosuppression. Geneva. 1998; [Abstract]. 130.
75. Vincenti F., Dacvlizumab/Combination Renal Transplant Study Group. 17th Annual Meeting of the American Society of Transplant Physicians (ASTP). Chicago. 1998. [Abstract].
76. Woellwarth J., Behrend M. et al. A new immunosupressive protocol with high dose Mycophenolate Mofetil for kidney transplantation in sensitive patients. The International Congress on Immunosuppression. Orlando. 1997; [Abstract105]. 165.
77. Woellwarth J., Behrend M. et al. A new immunosupressive protocol with high dose Mycophenolate Mofetil for kidney transplantation in sensitive patients. [Abstract 75].
78. Wombolt D.C. Use of Mycophenolate Mofetil in patients with chronic cyclosporine nephrotoxicity. The International Congress on Immunosuppression. Orlando. 1997; [Abstract 91]. 161.
79. Young C.J., Sollinger H.W. RS-61443: a new immunosuppressive agent. Transplant Proc. 1994; Vol.26; 3144-6.
80. Zanker B. et al. Mycophenolate mofetil (MMF) prevents de novo sensitisation of alloreactive B-cells in immunologic high risk renal transplant recepients. [Abstract 348]. 217.

Другие статьи по теме

• Морфологические особенности позднего отторжения трансплантированной почки и их влияние на течение и прогноз нефропатии
• Заместительная терапия терминальной хронической почечной недостаточности в Российской Федерации в 1998-2013 гг. Отчет по данным Российского регистра заместительной почечной терапии.Часть первая
• Уретеронеоцистоанастомоз с отсроченной эндовезикальной антирефлюксной защитой - новый метод профилактики пузырномочеточникового рефлюкса после трансплантации почки: рандомизированное клиническое исследование
• Успешное лечение рака функционирующего почечного трансплантата