nefrНефрологияNephrology (Saint-Petersburg)1561-62742541-9439Pavlov First Saint-Petersburg State Medical University10.24884/1561-6274-2017-21-6-39-47nefr-311Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИ. КЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯORIGINAL ARTICLES. CLINICAL INVESTIGATIONSПЕРВЫЙ РОССИЙСКИЙ ОПЫТ РАННЕЙ КОНВЕРСИИ НА ЭВЕРОЛИМУС ПРИ ТРАНСПЛАНТАЦИИ ПОЧЕК ОТ ДОНОРОВ С РАСШИРЕННЫМИ КРИТЕРИЯМИ. ОБОБЩЕНИЕ 5-ЛЕТНИХ РЕЗУЛЬТАТОВFIRST RUSSIAN EXPERIENCE OF EARLY CONVERSION TO EVEROLIMUS IN THE KIDNEY TRANSPLANTATION FROM EXPANDED CRITERIA DONORS: A SUMMARY OF 5-YEAR OBSERVATIONУльянкинаИ. В.UliyankinaI. V.

Ульянкина Ирина Владимировна - Городской центр органного и тканевого донорства.

192242, Санкт-Петербург,  ул.  Будапештская,  д.  3,  лит.  А., тел.: (812) 774-86-75

UlyankinaV. Irina - town center of organ and tissue donation.

192242, St. Petersburg, Budapest Str., Building 3, Lit. A, Tel.: (812) 774-86-75

irina-yl@mail.ruСкворцовА. Е.SkvortsovA. E.

Скворцов Андрей Евгениевич - кандидат медицинских наук, клиника научно-исследовательского института хирургии и неотложной медицины.

197022, Санкт-Петербург,  ул.  Л.  Толстого,  д.  17, корп. 54, тел.: (812) 346-39-26

Andrey E. Skvortsov - MD, PhD, Hospital Research Institute of Surgery and Emergency Medicine.

197022, St. Petersburg, L. Tolstoy st. 17, build. 54, Tel.: (812) 346-39-26

skvortsov.spb@gmail.comАнаньевА. Н.AnanievA. N.

Ананьев Алексей Николаевич - кандидат медицинских наук, клиника научно-исследовательского института хирургии и неотложной медицины.

197022, Санкт-Петербург,  ул.  Л.  Толстого,  д.  17, корп. 54, тел.: (812) 346-39-26

Alexey N. Ananiev - MD, PhD, Hospital Research Institute of Surgery and Emergency Medicine

197022, St. Petersburg, L. Tolstoy st. 17, build. 54, Tel.: (812) 346-39-26

alananiev@yandex.ruСусловД. Н.SuslovD. N.

Суслов Дмитрий Николаевич - кандидат медицинских наук

197022, Санкт-Петербург,  ул.  Л.  Толстого,  д.  17, корп. 54, тел.: (812) 346-39-26

Dmitriy N. Suslov - MD, PhD, klinika nauchnoissledovatel'skogo instituta khirurgii i neotlozhnoy meditsiny

197022, Sankt-Peterburg, ul. L. Tolstogo 17, korp. 54, Tel.: (812) 346-39-26

susloff.dmit@yandex.ruКутенковА. А.KutenkovA. A.

Кутенков Алексей Анатольевич - Городской центр органного и тканевого донорства.

192242,  Санкт-Петербург,  ул.  Будапештская,  д.  3,  лит.  А, тел.: (812) 774-86-75

AlexeyA. Kutenkov - St. Petersburg Organ procurement center.

192242, St. Petersburg, Budapeshstskaya st., build 3, Lit. A; Tel.: (812) 774-86-75

alexqut@gmail.comТутинА. П.TutinA. P.

Тутин Алексей Павлович - Городской центр органного и тканевого донорства.

192242, Санкт-Петербург, ул. Будапештская, д. 3, лит. А, тел.: (812) 774-86-75

Aleksey Pavlovich - Gorodskoy tsentr organnogo i tkanevogo donorstva.

192242, Sankt-Peterburg, Budapeshtskaya ul., dom 3, lit. A, Tel.: (812) 774-86-75

lexa20@mail.ruКузьминД. О.KuzminD. O.

Кузьмин Денис Олегович - Городской центр органного и тканевого донорства.

192242, Санкт-Петербург, ул. Будапештская, д. 3, лит. А.,тел.: (812) 774-86-75

Denis O. Kuzmin - St. Petersburg Organ procurement center.

192242, St. Petersburg, Budapeshstskaya st., Lit. A, Tel.: (812) 774-86-75

saintdeni@gmail.comДайнекоВ. С.DainekoV. S.

Дайнеко Василий Сергеевич - Городской центр органного и тканевого донорства.

192242,  Санкт-Петербург, ул.  Будапештская,  д.  3,  лит.  А., тел.: (812) 774-86-75

VasilyS. Dayneko - St. Petersburg Organ procurement center.

192242, St. Petersburg, Budapeshstskaya st., build 3, Lit. A, Tel.: (812) 774-86-75

dvsis@rambler.ruГоголевД. В.GogolevD. V.

ГоголевДенисВадимович – доктор медицинских наук, доцент, клиника научно-исследовательского института хирургии и неотложной медицины.

197022, Санкт-Петербург,  ул.  Л.  Толстого,  д.  17, корп.  54, тел.: (812) 346-39-26

Denis V. Gogolev - MD, DMedSci, Associate professor, klinika nauchnoissledovatel’skogo instituta khirurgii i neotlozhnoy meditsiny.

197022, Sankt-Peterburg, ul. L. Tolstogo17, korp. 54, Tel.: (812) 346-39-26

simplex5@mail.ruРезникО. Н.ReznikO. N.

Резник Олег Николаевич - доктор медицинских наук, доцент, клиника научно-исследовательского института хирургии и неотложной медицины.

197022, Санкт-Петербург,  ул.  Л.  Толстого,  д.  17, корп. 54, тел.: (812) 346-39-26

Oleg N. Reznik - MD, PhD; DMedSci, Associate professor, Hospital Research Institute of Surgery and Emergency Medicine

197022, St. Petersburg, L. Tolstoy st. 17, build. 54, Tel.: (812) 3463926

onreznik@gmail.comСанкт-Петербургский научно-исследовательский институт скорой помощи им И.И. Джанелидзе»РоссияSt. Petersburg Research Institute. II JanelidzeRussian FederationПервый Санкт-Петербургский медицинский университет им. акад. И. П. ПавловаРоссияThe First Pavlov St. Petersburg State Medical UniversityRussian FederationПервый Санкт-Петербургский медицинский университет им. акад. И. П. ПавловаРоссияPervyy Sankt-Peterburgskiy gosudarstvennyy meditsinskiy universitet im. akad. I.P. PavlovaRussian FederationСанкт-Петербургский научно-исследовательский институт скорой помощи им И.И. Джанелидзе»РоссияJanelidze St. Petersburg Research InstituteRussian FederationСанкт-Петербургский научно-исследовательский институт скорой помощи им И.И. Джанелидзе»РоссияTutin Sankt-Peterburgskiy nauchno-issledovatel'skiy institut im. I.I. DzhanelidzeRussian FederationСанкт-Петербургский научно-исследовательский институт скорой помощи им И.И. Джанелидзе»РоссияJanelidze St. Petersburg Research Institute.Russian Federation2017281120172163947Copyright © Ульянкина И.В., Скворцов А.Е., Ананьев А.Н., Суслов Д.Н., Кутенков А.А., Тутин А.П., Кузьмин Д.О., Дайнеко В.С., Гоголев Д.В., Резник О.Н., 20172017Ульянкина И.В., Скворцов А.Е., Ананьев А.Н., Суслов Д.Н., Кутенков А.А., Тутин А.П., Кузьмин Д.О., Дайнеко В.С., Гоголев Д.В., Резник О.Н.Uliyankina I.V., Skvortsov A.E., Ananiev A.N., Suslov D.N., Kutenkov A.A., Tutin A.P., 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.nephrolog.ru/jour/article/view/311Введение

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.

Пациенты и методы

Пациенты и методы. Были исследованы результаты пересадок контралатеральных почек (n=41), полученных от ДРК, из числа этих реципиентов были сформированы 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 минимизировалась доза стероидов у пациентов исследуемой группы.

Результаты

Результаты. Обе группы были сопоставимы по уровню  креатинина и СКФ до 3 мес после ТП. В результате введения новой схемы ИСТ в исследуемой группе к 60 мес после ТП креатинин составил 149±43 мкмоль/л, в группе сравнения – 210±40 мкмоль/л; р<0,05. В контрольной группе отмечалось снижение СКФ до 28±7  мл/мин/1,73 м2, в исследуемой – 46±15 мл/мин/1,73м2; 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 (IST) approach included m-TOR inhibitors in case of KTx from the ECD lead to decreasing levels of cyclosporine (CsA) in the blood. Despite of presence international pilot studies we having not yet strong recommendation for real  combination of CsA and  Everolimus. In this  article we presented 5-yeras results of the  first Russian experience of systematic use Everolimus as basic IST in KTx from  ECDs. 

Patients  and methods

Patients  and methods.  The group of recipients (n=41) was formed during the operation; received a bilateral kidney transplants from the same ECDs. Comparison group (n=19) received standard IST consisting of CsA, MMF and  steroids. Study group included 22 recipients who received an another kidney  from the same ECD and  IST, based on early (starting from the 90th  day after  transplantation) conversion from MMF to Everolimus-1.5mg/day (target concentration-3-6ng/mL). Simultaneously with the appointment Everolimus, dosing occurred immediately Neoral decrease by 50% and  then, in accordance with the target concentration (C0-30-50ng/ml). Implementing a program of gradual minimization of the dose steroids in patients of the study group.

Results

Results. Both groups were comparable in terms of level of serum creatinine and glomerular filtration rate of up to 3 months after transplantation. As a result of the introduction of a new scheme of ICN in the study group, for the 60-month observation GFR study group was 46±15 ml/min/1.73m2, the control is reduced to 28±7  ml/min/1.73m2;P<0.05.

Conclusion

Conclusion. Early administration of Everolimus is strongly recommended in all cases of the use of grafts for KTx obtained from the ECDs. This approach helps to minimize of nephrotoxity of CNT, provides the prevention of chronical transplant nephropathy, the  stable renal  function, and  contributes to the  survival and  renal  transplant recipients.

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