nefrНефрологияNephrology (Saint-Petersburg)1561-62742541-9439Pavlov First Saint-Petersburg State Medical Universitynefr-239Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИ. КЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯORIGINAL ARTICLES. CLINICAL INVESTIGATIONSЧАСТОТА ВЫЯВЛЕНИЯ И ПРОГНОЗ АНТИТЕЛЬНООПОСРЕДОВАННОГО ОТТОРЖЕНИЯ ПРИ АЛЛОТРАНСПЛАНТАЦИИ ПОЧКИINCIDENCE AND PROGNOSIS OF ANTIBODY-MEDIATED REJECTION IN KIDNEY ALLOGRAFTSДобронравовВ. А.DobronravovV. A.

Профессор Добронравов Владимир Александрович, доктор медицинских наук 

Научно-исследовательский институт нефрологии. 

197022, Россия, Санкт-Петербург, ул. Л. Толстого, д. 17.

Prof. Vladimir A. Dobronravov, MD, PhD, DSc 

Department of propedeutics of internal diseases and Research Institute of Nephrology of the Pavlov

dobronravov@nephrolog.ruХраброваМ. С.KhrabrovaM. S.

Храброва Мария Сергеевна, кандидат медицинских наук. 

Кафедра пропедевтики внутренних болезней, ассистент. 

197022, Россия, Санкт-Петербург, ул. Л. Толстого, д. 17, корп. 54

Maria S. Khrabrova, MD, PhD 

Department of Propedeutics of Internal Diseases, Assistant prof. 

197022, Russia, Saint-Petersburg, Str. Leo Tolstoy, 17 build 54. 

hrabrovamc@gmail.comМухаметдиноваА. О.MukhametdinovaA. O.

Мухаметдинова Анастасия Олеговна. Кафедра пропедевтики внутренних болезней.

197022, Россия, Санкт-Петербург, ул. Л. Толстого, д. 6/8. 

Anastasiya O. Muhametdinova 

Department of propedeutics of internal diseases, Associate prof. 

197022, Russia, Saint-Petersburg, Str. Leo Tolstoy, 6/8.

muhametdinovanastya@mail.ruСиповскийВ. Г.SipovskiyV. G.

Доцент Сиповский Василий Георгиевич, кандидат медицинских наук. 

Научно-исследовательский институт нефрологии. 

197022, Россия, Санкт-Петербург, ул. Л. Толстого, д. 6/8.

Vassili G. Sipovski MD, PhD. 

Department of propedeutics of internal diseases and Research Institute of Nephrology of the Pavlov

197089, Russia, Saint-Petersburg, Str. Leo Tolstoy, 17.

Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. ПавловаРоссияFirst Pavlov Saint Petersburg State Medical UniversityRussian Federation2016030320172068289Copyright © Добронравов В.А., Храброва М.С., Мухаметдинова А.О., Сиповский В.Г., 20172017Добронравов В.А., Храброва М.С., Мухаметдинова А.О., Сиповский В.Г.Dobronravov V.A., Khrabrova M.S., Mukhametdinova A.O., Sipovskiy V.G.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/239

ЦЕЛЬ ИССЛЕДОВАНИЯ: определить частоту выявления и исходы антительно-опосредованного отторжения (AMR, antibody-mediated rejection) при рутинном морфологическом и иммунологическом мониторировании. ПАЦИЕНТЫ И МЕТОДЫ. В исследование вошли 55 реципиентов аллографта почки (АП) согласно критериям включения: совместимость с донором по группе крови, отрицательный цитотоксический кросс-матч-тест, как минимум, три биопсии АП. Все реципиенты получили стандартную иммуносупрессивную терапию: глюкокортикостероиды, базиликсимаб, ингибиторы кальциневрина, микофенолата мофетил. Пациентам выполняли протокольные биопсии (3, 6, 12 мес и далее ежегодно) и/или по показаниям: отсроченная функция АП, подъем креатинина ≥25%, протеинурия ≥1 г/сут или ее нарастание. Биопсии оценивали согласно критериям Banff 2013. Скрининг донор-специфических антител выполняли иммуноферментным анализом, а мониторинг – с помощью мультиплексного анализа Luminex (xMAP Technology). Терапия AMR включала глюкокортикостероиды, плазмаобмен, внутривенный иммуноглобулин, ритуксимаб, бортезомиб. Утрату функции АП и возврат на диализ учитывали как исход. Прогноз аллотрансплантации (АТП) оценивали на основе анализа выживаемости методом Каплана–Мейера. Медиана периода наблюдения от АТП составила 65 (47; 80) мес. РЕЗУЛЬТАТЫ. Морфологические признаки AMR были выявлены в 13% биопсий (n=390), а критерии AMR Banff 2013 – у 45% реципиентов (n=25) в разные сроки посттрансплантационного периода. Острое AMR (aAMR) регистрировали у 13 реципиентов, а хроническое активное (сAMR) – у 12. Субклиническим течение AMR было в 48% случаев. Персистенцию AMR выявили у 56% больных, а хронификацию – у 77%, несмотря на проводимую терапию. Кумулятивная выживаемость пациентов в общей группе за период наблюдения составила 94,5%, выживаемость АП – 79%. Выживаемость АП при AMR была ниже, чем у больных без AMR (73% и 100%, plog-rank=0,016). Различий в выживаемости АП в группах с аAMR и cAMR, а также с клиническим и субклиническим течением AMR выявлено не было. ЗАКЛЮЧЕНИЕ. AMR может быть распространенной и недооцениваемой клинической проблемой, связанной со снижением сроков функционирования АП и эффективности АТП в целом. Своевременное выявление и лечение этого типа иммунного конфликта требует рутинного проведения иммунологического и морфологического мониторинга.

THE STUDY was aimed to define the incidence rate and outcomes of antibody-mediated rejection (AMR) in the routine morphological and immunological monitoring. PATIENTS AND METHODS. 55 recipients of kidney allograft (KA) were enrolled into the study according to inclusion criteria (AB0-compatibility, negative cytotoxic crossmatch, minimum 3 kidnеy allograft biopsies in posttransplant period). All patients were on standard immunosuppressive regimen: glucocorticosteroids, basiliximab, calcineurin inhibitors, mycophenolate mofetil. Protocol (on 3, 6, 12 months and then annually) and indicative (delayed graft function, increase of serum creatinine level of ≥25%, proteinuria ≥1 g/24h) KA biopsies were evaluated according to Banff classification 2013. Enzyme-linked immunosorbent and multiplex (Luminex; xMAP Technology) assays were applied for donor-specific antibodies screening and monitoring, respectively. The treatment of AMR included glucocorticosteroids, plasma exchange, intravenous immunoglobulin, rituximab, bortesomib. KA loss and return to dialysis were defined as an outcome. Long-term KA prognosis was estimated by Kaplan–Meier survival analysis. The median posttransplant follow-up was 65 (47; 80) months. RESULTS. Morphological features of AMR was established in 13% of biopsies (n=390) and 45% of patients met Banff 2013 AMR criteria. Acute AMR (aAMR) and chronic active (cAMR) were found in 13 and 12 KA recipients, respectively. 48% of cases showed subclinical type of AMR. Persistence and chronification of AMR were established in 56% and 77% of patients, respectively. Cumulative 9-year patient survival in the group studied (n=55) for the follow-up period was 94,5%, cumulative survival of KA was 79%. KA survival was worse in AMR patients when compared with the control group without AMR (73% vs 100%, plog-rank=0,016). There were no difference in KA survival in aAMR and cAMR as far as in clinical and subclinical types of AMR. CONCLUSION: AMR is supposed to be the frequent and under-recognized clinical problem associated with inferior KA survival and overall effectiveness of kidney allotransplantation. The approach to early diagnostic and treatment of this type of immune conflict requires the immunological and morphological monitoring of КА on a regular basis.

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