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 Federation10.15825/1995-1191-2018-3-13-19vtio-906Research ArticleКлиническая трансплантологияClinical TransplantologyДинамика предсуществующих анти-HLA -антител и результаты трансплантации почкиThe dynamics of pre-existing anti-HLA antibodies and the results of kidney transplantationВатазинА. В.VatazinA. V.ЗулькарнаевА. Б.ZulkarnaevA. B.

Адрес: 129110, Москва, ул. Щепкина, д. 61/2, корп. 6. Тел. (916) 705-98-99

Address: 61/2, bl. 6, Shchepkina st., Moscow, 129110, Russian Federation. Tel. (916) 705-98-99

7059899@gmail.comСтепановВ. А.StepanovV. A.ФедулкинаВ. А.FedulkinaV. A.ГБУЗ МО «Московский областной научно-исследовательский клинический институт им. М.Ф. Владимирского»РоссияM.F. Vladimirsky Moscow Regional Clinical and Research InstituteRussian Federation2018160920182031319Copyright © Ватазин А.В., Зулькарнаев А.Б., Степанов В.А., Федулкина В.А., 20182018Ватазин А.В., Зулькарнаев А.Б., Степанов В.А., Федулкина В.А.Vatazin A.V., Zulkarnaev A.B., Stepanov V.A., Fedulkina V.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/906Цель

Цель. Проанализировать связь между пиковым значением панель-реактивных антител (пик-PRA), значением на момент трансплантации (тр-PRA) и результатами трансплантации почки.

Материалы и методы

Материалы и методы. В исследование включено 287 пациентов из листа ожидания с анти- HLA-антителами I и/или II классов. 142 пациентам была выполнена трансплантация трупной  почки. Все пациенты получали стандартную иммуносупрессию: ингибитор кальциневрина,  микофенолаты и стероиды. Десенсибилизация в предоперационном периоде проводилась у 11  пациентов. Скрининг и идентификацию антител проводили при помощи мультиплексной технологии на платформе Luminex.

Результаты

Результаты. Медиана PRA составила 47% (интерквартильный размах – 29%; 65%). В  зависимости от динамики PRA мы выделили несколько групп пациентов: стабильное PRA (83  пациента), постепенно возрастающее (77 пациентов) или убывающее значение (96  пациентов), или была отмечена переменная динамика (31 пациент). Изменение PRA сопровождалось изменением средней интенсивности флюоресценции (r = 0,787, r2 = 0,59, p < 0,0001). При однофакторном анализе каждые 5% пик-PRA и тр-PRA увеличивали  относительный риск гуморального отторжения трансплантата – 1,09 (95% ДИ 1,06; 1,17), p <  0,001; 1,17 (95% ДИ 1,09; 1,26), p < 0,001 соответственно, а ΔPRA снижало – 0,932 (95% ДИ  0,861; 0,967), p = 0,009. При многофакторном анализе (с коррекцией на пол и возраст  реципиента, продолжительность диализа, количество HLA-несовпадений) мы наблюдали  похожую картину: пик-PRA 1,14 (95% ДИ 1,07; 1,19), p < 0,001; тр-PRA 1,13 (95% ДИ 1,09; 1,22), p < 0,001; ΔPRA 0,949 (95% ДИ 0,871; 0,981), p = 0,017. В однофакторной модели увеличение пикPRA и тр-PRA повышало риск утраты трансплантата – 1,1 (95% ДИ 1,05; 1,14),  p < 0,001; 1,09 (95% ДИ 1,05; 1,15), p < 0,001 соответственно, а увеличение ΔPRA снижало –  0,952 (95% ДИ 0,891; 0,97), p = 0,011. В скорректированной многофакторной модели тр-PRA  не было сопряжено с риском утраты трансплантата – 1,04 (95% ДИ 0,95; 1,1), p = 0,098, в то  время как пик-PRA и ΔPRA оставались значимыми факторами – 1,1 (95% ДИ 1,17; 1,24), p < 0,001; 0,931 (95% ДИ 0,855; 0,954), p = 0,007 соответственно.

Заключение

Заключение. При подборе пар «донор–реципиент» необходимо учитывать спектр антител в  момент пикового (наивысшего) значения PRA. Уменьшение этого показателя может скрывать  антитела, которые имеют направленность против донорских антигенов или определенных эпитопов.

Aim

Aim. To analyze the relationship between the peak panel-reactive antibodies (peak-PRA), the value at the time of transplantation (Tx-PRA) and the results of kidney transplantation.

Materials and methods

Materials and methods. The study included 287 patients from the waiting list  with anti-HLA antibodies of I and/or II classes. 142 patients underwent transplantation of a cadaveric kidney. All patients received standard  immunosuppression: a calcineurin inhibitor, mycophenolate and steroids.  Desensitization in the preoperative period was carried out in 11 patients.  Screening and identification of antibodies was performed using multiplex technology on Luminex platform.

Results

Results. The median PRA was 47% (interquartile range – 29%; 65%).  Depending on the dynamics of PRA, we identified several groups of patients:  stable PRA (83 patients), increasing (77 patients) or decreasing value (96  patients), or variable dynamics (31 patients). The change in PRA was  accompanied by a change in the mean fluorescence intensity (r = 0.787, r2 =  0.59, p < 0.0001). In the univariate analysis, each 5% of peak-PRA and Tx-PRA  increased the relative risk (RR) of humoral graft rejection (1.09 (95%CI 1.06;  1.17), p < 0.001; 1.17 (95%CI 1.09; 1.26), p < 0.001 respectively), and ΔPRA  decreased a RR (0.932 (95% CI 0.861; 0.967), p = 0.009). In multivariate analysis (adjusted for sex and age of recipient, duration of dialysis, number of  HLA mismatches), we observed a similar scenario: peak-PRA 1.14 (95% CI 1.07; 1.19), p < 0.001; Tx-PRA 1.13 (95% CI 1.09; 1.22), p < 0.001; ΔPRA 0.949  (95% CI 0.871; 0.981), p = 0.017. In the univariate analysis increases in peak- PRA and Tx-PRA increased aRR of graft loss (1.1 (95% CI 1.05; 1.14), p <  0.001; 1.09 (95% CI 1.05; 1.15), p < 0.001 respectively), and increase in ΔPRA  decreased RR (0.952 (95% CI 0.891; 0.97), p = 0.011). In the adjusted  multivariate model, Tx-PRA did not increasea RR of graft loss (1.04 (95% CI,  0.95; 1.1), p = 0.098), while peak-PRA and ΔPRA remained significant factors  (1.1 (95% CI, 1.17; 1.24), p < 0.001; 0.931 (95% CI, 0.855; 0.954), p =  0.007, respectively).

 

 

Conclusion

Conclusion. In the selection donor-recipient pair it is necessary to take into account the spectrum of antibodies at the point of peak values of PRA. A  decrease in PRA may hide antibodies that have a specificity to donor antigens or on certain epitope.

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