vtioВестник трансплантологии и искусственных органовRussian Journal of Transplantology and Artificial Organs1995-1191Academician V.I.Shumakov National Medical Research Center of Transplantology and Artificial Organs", Ministry of Health of the Russian Federation10.15825/1995-1191-2016-4-77-86vtio-703Research ArticleКлиническая трансплантологияClinical TransplantologyОБОБЩЕНИЕ ПЕРВОГО В РОССИЙСКОЙ ФЕДЕРАЦИИ ОПЫТА СИСТЕМАТИЧЕСКОГО НАЗНАЧЕНИЯ ЭВЕРОЛИМУСА ПРИ ТРАНСПЛАНТАЦИИ ПОЧЕК ОТ ДОНОРОВ С РАСШИРЕННЫМИ КРИТЕРИЯМИFIRST EXPERIENCE IN SYSTEMIC ADMINISTRATION OF EVEROLIMUS IN RENAL TRANSPLANTATION FROM EXPANDED CRITERIA DONORS IN RUSSIAN FEDERATIONУльянкинаИ. В.UliyankinaI. V.

Санкт-Петербург, Российская Федерация

Saint Petersburg, Russian Federation

СкворцовА. Е.SkvortsovA. E.

Санкт-Петербург, Российская Федерация

Saint Petersburg, Russian Federation

АнаньевА. Н.AnanievA. N.

Санкт-Петербург, Российская Федерация

Saint Petersburg, Russian Federation

КутенковА. А.KutenkovA. A.

Санкт-Петербург, Российская Федерация

Saint Petersburg, Russian Federation

КузьминД. О.KuzminD. O.

Санкт-Петербург, Российская Федерация

Saint Petersburg, Russian Federation

ДайнекоВ. С.DainekoV. S.

Санкт-Петербург, Российская Федерация

Saint Petersburg, Russian Federation

ГоголевД. В.GogolevD. V.

Санкт-Петербург, Российская Федерация

Saint Petersburg, Russian Federation

РезникО. Н.ReznikO. N.

Адрес: 197022, Санкт-Петербург, ул. Льва Толстого, д. 6–8. Тел. (921) 935-51-91

Address: 6–8, Lev Tolstoy st., Saint Petersburg, 197022, Russian Federation. Теl. (921) 935-51-91

onreznik@gmail.comГБУ «Санкт-Петербургский научно-исследовательский институт скорой помощи им. И.И. Джанелидзе»РоссияSaint-Petersburg I.I. Dzhanelidze State Research Institute of Emergency MedicineRussian FederationФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет им. академика И.П. Павлова» Минздрава РоссииРоссияPavlov First Saint Petersburg State Medical UniversityRussian FederationГБУ «Санкт-Петербургский научно-исследовательский институт скорой помощи им. И.И. Джанелидзе» ФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет им. академика И.П. Павлова» Минздрава РоссииРоссияSaint-Petersburg I.I. Dzhanelidze State Research Institute of Emergency Medicine Pavlov First Saint Petersburg State Medical UniversityRussian Federation2016280120171847786Copyright © Ульянкина И.В., Скворцов А.Е., Ананьев А.Н., Кутенков А.А., Кузьмин Д.О., Дайнеко В.С., Гоголев Д.В., Резник О.Н., 20172017Ульянкина И.В., Скворцов А.Е., Ананьев А.Н., Кутенков А.А., Кузьмин Д.О., Дайнеко В.С., Гоголев Д.В., Резник О.Н.Uliyankina I.V., Skvortsov A.E., Ananiev A.N., Kutenkov A.A., Kuzmin D.O., Daineko V.S., Gogolev D.V., Reznik O.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.transpl.ru/vtio/article/view/703Введение

Введение. Увеличение доли трансплантатов, полученных от доноров с расширенными критериями (ДРК), ставит вопрос об оптимизации схем иммуносупрессивной терапии (ИСТ). Применение схем с включением m-TOR-ингибиторов при трансплантации почек (Тх почек) от ДРК позволяет снизить уровень циклоспорина (ЦсА), минимизируя его нефротоксичность. В настоящее время отсутствует четкий алгоритм использования комбинации ЦсА и эверолимуса в различных клинических ситуациях. Нами предпринята попытка обобщить собственный, первый в России, 5-летний опыт применения эверолимуса.

Материалы и методы

Материалы и методы. Были исследованы результаты пересадок контралатеральных почек (n = 41), полученных от ДРК, из числа этих реципиентов была сформирована группа сравнения (n = 19), пациенты которой получали стандартную ИСТ (ЦсА, микофенолаты, стероиды), и исследуемая группа (n = 22), пациенты которой получили контралатеральную почку и иммуносупрессию, с ранней (начиная с 90-го дня после ТП) конверсией от ММФ на эверолимус в дозе 1,5 мг/сут (целевая концентрация – 3–6 нг/мл). Одновременно с назначением эверолимуса снижалась дозировка неорала сразу на 50%, а затем в соответствии с целевой концентрацией (С0 30–50 нг/мл). Постепенно минимизировались доза стероидов у пациентов исследуемой группы.

Результаты

Результаты. Обе группы были сопоставимы по уровню креатинина и СКФ до 3 месяцев после ТП. В результате введения новой схемы ИСТ в исследуемой группе к 60 месяцам после ТП креатинин составил 149,27 ± 42,68 мкмоль/л, в группе сравнения – 209,87 ± 39,56 мкмоль/л; р < 0,05. В контрольной группе отмечалось снижение СКФ до 27,50 ± 7,39 мл/мин/1,73 м2, в исследуемой – 46,21 ± 15,17 мл/мин/1,73 м2; р < 0,05.

Выводы

Выводы. Ранняя конверсия на эверолимус показана в случаях Тх почек, полученных от ДРК. Разработанная схема позволяет минимизировать дозу ИКН, что снижает проявления нефротоксичности, без ущерба для общей эффективности терапии, обеспечивает профилактику ХТН, стабильную функцию почек в долгосрочном периоде, способствует выживаемости реципиентов и почечных трансплантатов.

Introduction

Introduction. Kidney transplant (KTx) with reduced functional reserve is more sensitive to the toxic effects of calcineurin inhibitors (CNI). Immunosuppressive therapy (IST) approach with m-TOR inhibitors in case of KTx from expanded criteria donors (ECD) leads to decreasing levels of cyclosporine (CsA) in the blood. Despite the presence of international pilot studies we do not have yet clear recommendation as to combination of CsA and Everolimus. In this article, we presented 5-year results of the fi rst Russian experience of systematic administration of Everolimus as a basic IST in KTx from ECDs.

Materials and methods

Materials and methods. The group of recipients (n = 41) having received bilateral kidney transplants from the same ECDs was analyzed. Comparison group (n = 19) received standard IST consisting of CsA, MMF and steroids. Study group included 22 recipients who received kidneys from the same ECDs and IST based on early (starting from the 90th day after transplantation) conversion from MMF to Everolimus – 1.5 mg/day (target concentration – 3–6 ng/mL). Simultaneously with the administration of Everolimus, dosing of Neoral dropped immediately by 50%, and then, in accordance with the target concentration (C0 30–50 ng/mL). Dosage of steroids in patients of the study group was gradually minimized.

Results

Results. Both groups were comparable in terms of serum creatinine level and glomerular fi ltration rate (GFR) up to 3 months after transplantation. As a result of the introduction of a new IST scheme in the study group, serum creatinine level in 60 months after KTx was 149.27 ± 42.68 μmol/L, in the comparison group – 209.87 ± 39.56 μmol/L; р < 0.05. In the control group GFR reduced to 27.50 ± 7.39 mL/min/1.73 m2, in the study group it was 46.21 ± 15.17 mL/min/1.73 m2, p < 0.05.

Conclusion

Conclusion. Early administration of Everolimus is strongly recommended in all cases of ECD KTx. This approach helps minimize CNI nephrotoxicity, provides the prevention of chronic allograft nephropathy, enables the stable renal function, and contributes to the survival of renal transplant recipients.

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