nidНефрология и диализNephrology and Dialysis1680-44222618-9801Российское диализное обществоnid-2001Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESРациональное использование рапамицина (сиролимуса) в современной многокомпонентной иммуносупрессии при трансплантации почкиRational use of rapamycin (sirolimus) in modern multicomponent immunosupression after kidney transplantationКаабакМ. М.KaabakM. M.kaabak@hotmail.comСамсоновД. В.SamsonovD. V.noemail@neicon.ruБабенкоН. Н.BabenkoN. N.noemail@neicon.ruШереметьеваГ. Ф.SheremetievaG. F.noemail@neicon.ruМорозоваМ. М.MorozovaM. M.noemail@neicon.ruКуракинаЖ. И.KurakinaJ. I.noemail@neicon.ruЧепрасоваТ. Ю.CheprasovaT. U.noemail@neicon.ruРоссийский научный центр хирургии РАМН, г. МоскваRussian Federation20032706202554379387Copyright © Каабак М.М., Самсонов Д.В., Бабенко Н.Н., Шереметьева Г.Ф., Морозова М.М., Куракина Ж.И., Чепрасова Т.Ю., 20252025Каабак М.М., Самсонов Д.В., Бабенко Н.Н., Шереметьева Г.Ф., Морозова М.М., Куракина Ж.И., Чепрасова Т.Ю.Kaabak M.M., Samsonov D.V., Babenko N.N., Sheremetieva G.F., Morozova M.M., Kurakina J.I., Cheprasova T.U.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.nephro.ru/jour/article/view/2001

Проведено исследование возможности использования рапамицина в составе протокола иммуносупрессии, позволяющего провести раннюю отмену циклоспорина у пациентов после трансплантации почки. Рапамицин был назначен 10 пациентам. При средней продолжительности наблюдения 179 ± 61 день отсутствует летальность и нет потерь трансплантатов. Одному пациенту рапамицин был отменен на 19-е сутки в связи с гастроинтестинальными побочными эффектами. Оставшимся 9 пациентам перед началом отмены циклоспорина выполняли пункционную биопсию. У пятерых обнаружены морфологические признаки острого отторжения, потребовавшие изменения протокола иммуносупрессии. Рапамицин является эффективным иммуносупрессантом, который может использоваться у пациентов после трансплантации почки вместо циклоспорина в комбинации со стероидами у 30% пациентов. Еще у 30% пациентов требуется комбинирование рапамицина, селлсепта и стероидов.

The possibility to use rapamycin in immunosuppressive protocol, allowing early cyclosporine withdrawal in kidney transplant recipients, was investigated. Rapamycin was administered in 10 patients. There were no patient’s deaths and graft lost during follow-up period (179 ± 61 days). In one case rapamycin was stopped on day 19 because of gastrointestinal side effects. In the rest 9 cases before start of cyclosporine withdrawal graft biopsy was performed. In 5 patients morphological signs of acute rejection were found and demanded change of immunosuppressive drug combination. Rapamycin is effective immunosuppressive drug that can be used in kidney transplant recipients instead of cyclosporine in 30% of patients. Another 30% patients demand combination of rapamycin, MMF and steroids.

рапамициниммуносупрессиятрансплантация почкиострое отторжениеReferencesBarone G.W., Gurley B.J., Abul-Ezz S.R., Gokden N. Sirolimus-induced thrombotic microangiopathy in a renal transplant recipient. Am J Kidney Dis 2003; 42 (1): 202-206.Barone G.W., Gurley B.J., Abul-Ezz S.R., Gokden N. Sirolimus-induced thrombotic microangiopathy in a renal transplant recipient. Am J Kidney Dis 2003; 42 (1): 202-206.Brazelton T.R., Morris R.E. Molecular mechanisms of action of new xenobiotic immunosuppressive drugs: tacrolimus (FK506), sirolimus (rapamycin), mycophenolate mofetil and leflunomide. Curr Opin Immunol 1996; 8: 710-720.Brazelton T.R., Morris R.E. Molecular mechanisms of action of new xenobiotic immunosuppressive drugs: tacrolimus (FK506), sirolimus (rapamycin), mycophenolate mofetil and leflunomide. Curr Opin Immunol 1996; 8: 710-720.Dumont F.J., Staruch M.J., Koprak S.L. et al. Distinct mechanisms of suppression of murine T-cell activation by the related macrolides FK-506 and rapamycin. J Immunol 1990; 144: 251-258.Dumont F.J., Staruch M.J., Koprak S.L. et al. Distinct mechanisms of suppression of murine T-cell activation by the related macrolides FK-506 and rapamycin. J Immunol 1990; 144: 251-258.Flechner S.M., Goldfarb D., Modlin C., Feng J., Krishnamurthi V., Mastroianni B., Savas K., Cook D.J., Novick A.C. Kidney transplantation without calcineurin inhibitor drugs: a prospective, randomized trial of sirolimus versus cyclosporine. Transplantation 2002; 74 (8): 1070-1076.Flechner S.M., Goldfarb D., Modlin C., Feng J., Krishnamurthi V., Mastroianni B., Savas K., Cook D.J., Novick A.C. Kidney transplantation without calcineurin inhibitor drugs: a prospective, randomized trial of sirolimus versus cyclosporine. Transplantation 2002; 74 (8): 1070-1076.El-Sabrout R., Weiss R., Butt F., Delaney V., Qadir M., Hanson P., Butt K. Rejection-free protocol using sirolimus-tacrolimus combination for pediatric renal transplant recipients. Transplant Proc 2002; 34 (5): 1942-1943.El-Sabrout R., Weiss R., Butt F., Delaney V., Qadir M., Hanson P., Butt K. Rejection-free protocol using sirolimus-tacrolimus combination for pediatric renal transplant recipients. Transplant Proc 2002; 34 (5): 1942-1943.Guilbeau J.M. Delayed wound healing with sirolimus after liver transplant. Ann Pharmacother 2002; 36 (9): 1391-1395.Guilbeau J.M. Delayed wound healing with sirolimus after liver transplant. Ann Pharmacother 2002; 36 (9): 1391-1395.Johnson R.W.G., Kreis H., Oberbauer R. et al. Sirolimus allows early cyclosporine withdrawal in renal transplantation resulting in improved renal function and lower blood pressure. Transplantation 2001; 72: 777-786.Johnson R.W.G., Kreis H., Oberbauer R. et al. Sirolimus allows early cyclosporine withdrawal in renal transplantation resulting in improved renal function and lower blood pressure. Transplantation 2001; 72: 777-786.Johnson R.W., Kreis H., Oberbauer R., Brattström C., Claesson K., Eris J. Sirolimus allows early cyclosporine withdrawal in renal transplantation resulting in improved renal function and lower blood pressure. Transplantation 2001; 72 (5): 777-786.Johnson R.W., Kreis H., Oberbauer R., Brattström C., Claesson K., Eris J. Sirolimus allows early cyclosporine withdrawal in renal transplantation resulting in improved renal function and lower blood pressure. Transplantation 2001; 72 (5): 777-786.King-Biggs M.B., Dunitz J.M., Park S.J., Kay Savik S., Hertz M.I. Airway anastomotic dehiscence associated with use of sirolimus immediately after lung transplantation. Transplantation 2003; 75 (9): 1437-1443.King-Biggs M.B., Dunitz J.M., Park S.J., Kay Savik S., Hertz M.I. Airway anastomotic dehiscence associated with use of sirolimus immediately after lung transplantation. Transplantation 2003; 75 (9): 1437-1443.Lo A., Egidi M.F., Gaber L.W., Gaber A.O. Observations on the use of sirolimus and tacrolimus in high-risk renal transplant recipients. Transplant Proc 2003; 35 (3 Suppl): S105-S108.Lo A., Egidi M.F., Gaber L.W., Gaber A.O. Observations on the use of sirolimus and tacrolimus in high-risk renal transplant recipients. Transplant Proc 2003; 35 (3 Suppl): S105-S108.Mahalati K., Murphy D.M., West M.L. Bronchiolitis obliterans and organizing pneumonia in renal transplant recipients. Transplantation 2000; 69 (7): 1531-1532.Mahalati K., Murphy D.M., West M.L. Bronchiolitis obliterans and organizing pneumonia in renal transplant recipients. Transplantation 2000; 69 (7): 1531-1532.Morelon E., Kreis H. Sirolimus therapy without calcineurin inhibitors: Necker Hospital 8-year experience. Transplant Proc 2003; 35 (3); (Suppl 1): S52-S57.Morelon E., Kreis H. Sirolimus therapy without calcineurin inhibitors: Necker Hospital 8-year experience. Transplant Proc 2003; 35 (3); (Suppl 1): S52-S57.Morelon E., Stern M., Israёl-Biet D., Correas J.M., Danel C., Mamzer-Bruneel M.F., Peraldi M.N., Kreis H. Characteristics of sirolimus-associated interstitial pneumonitis in renal transplant patients. Transplantation 2001; 72 (5): 787-790.Morelon E., Stern M., Israёl-Biet D., Correas J.M., Danel C., Mamzer-Bruneel M.F., Peraldi M.N., Kreis H. Characteristics of sirolimus-associated interstitial pneumonitis in renal transplant patients. Transplantation 2001; 72 (5): 787-790.Morris R.E. Mechanisms of action of new immunosupressive drugs. Ther Drug Monitor 1995; 17: 564-569.Morris R.E. Mechanisms of action of new immunosupressive drugs. Ther Drug Monitor 1995; 17: 564-569.Morrisett J.D., Abdel-Fattah G., Kahan B.D. Sirolimus changes lipid concentrations and lipoprotein metabolism in kidney transplant recipients. Transplant Proc 2003; 35 (3 Suppl): S143-S150.Morrisett J.D., Abdel-Fattah G., Kahan B.D. Sirolimus changes lipid concentrations and lipoprotein metabolism in kidney transplant recipients. Transplant Proc 2003; 35 (3 Suppl): S143-S150.Oberbauer R., Hutchison B., Eris J., Arias M., Claesson K., Mota A., Kreis H., Kleinman L., Wang F., Chen J., Revicki D.A. Health-related quality-of-life outcomes of sirolimus-treated kidney transplant patients after elimination of cyclosporine A: results of a 2-year randomized clinical trial. Transplantation 2003; 75; 8: 1277-1285.Oberbauer R., Hutchison B., Eris J., Arias M., Claesson K., Mota A., Kreis H., Kleinman L., Wang F., Chen J., Revicki D.A. Health-related quality-of-life outcomes of sirolimus-treated kidney transplant patients after elimination of cyclosporine A: results of a 2-year randomized clinical trial. Transplantation 2003; 75; 8: 1277-1285.Oberbauer R., Kreis H., Johnson R.W.G. et al. Long-term improvement in renal function is shown in patients treated with sirolimus (Rapamune®) and cyclosporine withdrawal: 2-year results of the Rapamune® Maintenance Regimen Trial. Transplantation 2002; 74 (4): abs 254.Oberbauer R., Kreis H., Johnson R.W.G. et al. Long-term improvement in renal function is shown in patients treated with sirolimus (Rapamune®) and cyclosporine withdrawal: 2-year results of the Rapamune® Maintenance Regimen Trial. Transplantation 2002; 74 (4): abs 254.Saunders R.N., Bicknell G.R., Nicholson M.L. The impact of cyclosporine dose reduction with or without the addition of rapamycin on functional, molecular, and histological markers of chronic allograft nephropathy. Transplantation 2003; 75 (6): 772-780.Saunders R.N., Bicknell G.R., Nicholson M.L. The impact of cyclosporine dose reduction with or without the addition of rapamycin on functional, molecular, and histological markers of chronic allograft nephropathy. Transplantation 2003; 75 (6): 772-780.Serkova N., Litt L., James T.L., Sadee W., Leibfritz D., Benet L.Z., Christians U. Evaluation of individual and combined neurotoxicity of the immunosuppressants cyclosporine and sirolimus by in vitro multinuclear NMR spectroscopy. J Pharmacol Exp Ther 1999; 289 (2): 800-806.Serkova N., Litt L., James T.L., Sadee W., Leibfritz D., Benet L.Z., Christians U. Evaluation of individual and combined neurotoxicity of the immunosuppressants cyclosporine and sirolimus by in vitro multinuclear NMR spectroscopy. J Pharmacol Exp Ther 1999; 289 (2): 800-806.Stepkowski S.M. Preclinical results of sirolimus treatment in transplant models. Transplant Proc 2003; 35 (3 Suppl): S219-S226.Stepkowski S.M. Preclinical results of sirolimus treatment in transplant models. Transplant Proc 2003; 35 (3 Suppl): S219-S226.

The authors declare that there are no conflicts of interest present.