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 Federation10.15825/1995-1191-2017-4-16-26vtio-823Research ArticleКлиническая трансплантологияClinical TransplantologyЭффективность поздней конверсии с микофенолатов на эверолимус у реципиентов почечного трансплантата с сопутствующими онкологическими заболеваниямиEfficiency of late conversion from mycophenolate mofetil to everolimus in kidney graft recipients with posttransplant malignancyКимИ. Г.KimI. G.

Москва.

Moscow.

kig21@rambler.ruТомилинаН. А.TomilinaN. A.

Москва.

Moscow.

ФедороваН. Д.FedorovaN. D.

Москва.

Moscow.

ОстровскаяИ. В.OstrovskayaI. V.

Москва.

Moscow.

СкрябинаИ. А.SkryabinaI. A.

Москва.

Moscow.

ФГБУ «Национальный медицинский исследовательский центр трансплантологии и искусственных органов имени академика В.И. Шумакова» Минздрава России; ФБУН «Московский научно-исследовательский институт эпидемиологии и микробиологии им. Г.Н. Габричевского» Роспотребнадзора.РоссияV.I. Shumakov National Medical Research Center of Transplantology and Artifi cial Organs of the Ministry of Healthcare of the Russian Federation; G.N. Gabrichevsky Moscow Research Institute of Epidemiology and Microbiology.Russian FederationФГБУ «Национальный медицинский исследовательский центр трансплантологии и искусственных органов имени академика В.И. Шумакова» Минздрава России; Московский государственный медико-стоматологический университет им. А.И. Евдокимова.РоссияV.I. Shumakov National Medical Research Center of Transplantology and Artifi cial Organs of the Ministry of Healthcare of the Russian Federation; A.I. Evdokimov Moscow State Medical Stomatological University.Russian FederationГБУЗ «Городская клиническая больница № 52» Департамента здравоохранения города Москвы».РоссияCity Hospital № 52.Russian Federation2017300120181941626Copyright © Ким И.Г., Томилина Н.А., Федорова Н.Д., Островская И.В., Скрябина И.А., 20182018Ким И.Г., Томилина Н.А., Федорова Н.Д., Островская И.В., Скрябина И.А.Kim I.G., Tomilina N.A., Fedorova N.D., Ostrovskaya I.V., Skryabina I.A.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/823

Новообразования наряду с сердечно-сосудистыми и инфекционными заболеваниями входят в число ведущих причин смерти реципиентов с функционирующим почечным трансплантатом. Одним из подходов к решению этой проблемы считают применение ингибиторов пролиферативного сигнала (ИПС), которое снижает частоту онкологических осложнений в сравнении с традиционной иммуносупрессией.

Цель исследования

Цель исследования: изучение эффективности и безопасности применения эверолимуса в сочетании с минимизированной дозой ингибиторов кальциневрина у пациентов с посттрансплантационными новообразованиями.

Материалы и методы

Материалы и методы. В исследование включены 62 реципиента почечного трансплантата (РПТ), которым в связи с диагностированным онкологическим заболеванием через 83,5 ± 69,3 мес. после трансплантации почки выполнялась конверсия с микофенолатов на эверолимус. Длительность наблюдения после конверсии составила 35,5 ± 26,9 мес. Эффективность терапии оценивали по выживаемости реципиентов и методики иммуносупрессии, динамике функции трансплантата и протеинурии. Выживаемость реципиентов сравнивали с выживаемостью в группе исторического контроля (n = 145), в которой онкобольные эверолимус не получали.

Результаты

Результаты. 10- и 15-летняя выживаемость РПТ в группе конверсии составила 92 и 85,7%, в то время как в группе контроля этот показатель снижался до 61,1 и 52,8% соответственно (p < 0,0003). Выживаемость методики иммуносупрессии через 1 год после начала терапии составила 86,5%, через 3 года – 64,2%, а к концу 5-го года вероятность продолжения лечения эверолимусом снижалась до 50,8%, главным образом, вследствие развития протеинурии и других нежелательных явлений. Частота рецидивов опухолей среди продолжавших терапию в течение 35 (26; 60) мес. составила 13,2%. Сывороточный креатинин в динамике повысился с 0,13 ± 0,04 до 0,15 ± 0,09 ммоль/л, p < 0,031, а суточная протеинурия – с 0,18 ± 0,25 до 0,75 ± 1,63 г/сут, p < 0,011.

Заключение

Заключение. Применение ИПС у РПТ с онкологическими заболеваниями достоверно повышает отдаленную выживаемость больных в сравнении с контрольной группой и демонстрирует относительно невысокую частоту рецидивов (13,2% случаев) новообразований в течение 35 мес. терапии. Вместе с тем применение ИПС возможно не у всех пациентов и уже через 5 лет после его начала прерывается почти у половины из них в связи с нарастающей протеинурией и серьезными нежелательными явлениями. 

Malignancy is one of the leading causes of death in recipients with a kidney grafts. The use of proliferative signal inhibitors (PSI) is one of the approaches to solve this problem.

Aim

Aim: to evaluate the effi cacy and safety of everolimus in combination with reduced dose of calcineurin inhibitors (CNI) in patients with posttransplant malignancy.

Materials and methods

Materials and methods. 62 kidney graft recipients (KGR) with neoplasia were converted from mycophenolate mofetil to everolimus in combination with reduced dose of CNI at 83.5 ± 69.3 months after transplantation. The duration follow-up was 35.5 ± 26.9 month. The effectiveness of management was assessed by patient survival, type of immunosuppression therapy, renal function and proteinuria. The patient survival in PSI group was compared with the survival in the patients in control group (n = 145), who did not receive everolimus.

Results

Results. 10-year and 15-year patient survival was 92% and 85,7% in patients treated with PSi versus 61.1% and 52.8% in control group (p < 0.0003). Patients survival with everolimus-therapy after 1 year was 86.5%, after 3 year it was 64.2%, and by the end of 5 years the possibility of treatment with everolimus decreased to 50.8%, mainly due to the proteinuria and other adverse events. The recurrence rate of tumors among patients, who was treated with everolimus for 35 (26; 60) months was 13.2%. Creatinine level in serum increased from 0.13 ± 0.04 to 0.15 ± 0.09 mmol during the treatment (p < 0.031), and the daily proteinuria increased from 0.18 ± 0.25 g/day to 0.75 ± 1.63 g/day, p < 0.011.

Conclusion

Conclusion. The usage of PSi improves long-term survival of KTR with posttransplant malignancy and demonstrates a relatively low tumors recurrence rate (13.2%) over a period of 35 months. However this treatment is not suitable for many patients and it was stopped in almost half of them due to increasing proteinuria or serious adverse events. 

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