nidНефрология и диализNephrology and Dialysis1680-44222618-9801Российское диализное обществоnid-1977Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESК вопросу об оптимизации мониторинга терапии препаратами циклоспорина в поздние сроки после аллотрансплантации почкиAn approach to optimization of monitoring of CyA therapy in long term kidney transplant recipientsСтоляревичЕ. С.StoliarevichE. S.natomil@online.ruСухановА. В.SukhanovA. V.noemail@neicon.ruБагдасарянА. Р.BagdasaryanA. R.noemail@neicon.ruБарановаФ. С.BaranovaF. S.noemail@neicon.ruПоповаЛ. К.PopovaL. K.noemail@neicon.ruФедороваН. Д.FiodorovaN. D.noemail@neicon.ruТомилинаН. А.TomilinaN. A.noemail@neicon.ruНИИ трансплантологии и искусственных органов Минздрава РФ, МоскваRussian Federation20042706202562145154Copyright © Столяревич Е.С., Суханов А.В., Багдасарян А.Р., Баранова Ф.С., Попова Л.К., Федорова Н.Д., Томилина Н.А., 20252025Столяревич Е.С., Суханов А.В., Багдасарян А.Р., Баранова Ф.С., Попова Л.К., Федорова Н.Д., Томилина Н.А.Stoliarevich E.S., Sukhanov A.V., Bagdasaryan A.R., Baranova F.S., Popova L.K., Fiodorova N.D., Tomilina N.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.nephro.ru/jour/article/view/1977

Циклоспорин А (СуА) является на сегодняшний день одним из основных компонентов иммуносупрессивной терапии после аллотрансплантации почки (АТП). Поскольку циклоспорин является препаратом «критичной дозы», при его использовании требуется постоянный мониторинг концентрации препарата в крови. Однако традиционная схема мониторинга с определением концентрации СуА натощак (до приема, С0) не всегда адекватно отражает экспозицию препарата в организме. Целью данного исследования было сравнить эффективность различных схем мониторинга терапии СуА, выяснить значение основных фармакокинетических параметров для предупреждения поздних кризов отторжения и СуА-нефротоксичности и определить оптимальные значения этих показателей в поздние сроки после АТП. Было выполнено 123 фармакокинетических исследования у 83 пациентов в поздние сроки после аллотрансплантации почки. В зависимости от клинико-функционального состояния трансплантата все пациенты были разделены на 4 группы. При сравнении фармакокинетических параметров в этих группах выяснилось, что, несмотря на отсутствие различий в уровне С0, показатели AUC, Cmax и C2 при кризе отторжения оказались значимо ниже, а при СуА-нефротоксичности - выше, чем при стабильной функции трансплантата. Частота этих осложнений оказалась минимальной при значениях AUC от 3000 до 4000 нг/мл/ч. Из всех определяемых точек фармакокинетической кривой наиболее тесная корреляция с AUC была получена для С3 (r2 = 0,68) и C2 (r2 = 0,65). Однако точность оценки экспозиции СуА еще более возрастала при расчете AUC по формуле с использованием С0, С1 и С3 (r2 = 0,89).

The Cyclosporine-based therapy is the most used immunosupression in kidney transplantation. The efficacy of cyclosporine therapy has been improved by monitoring drug concentration. But routine trough level which is still widely used to guide dose adjustment correlates poorly with the total drug exposure and with clinical events in patients after kidney transplantation. The aim of the study was to compare two different schemes of CyA-monitoring (С0, С2 and C0 + C1 + C3), to correlate cyclosporine pharmacokinetics and both kidney graft function and pathology in long-term kidney transplant recipients. 123 CsA pharmacokinetic studies were performed in 83 recipients. The patients were divided into 4 groups: 1 - stable graft function (n = 28); 2 - chronic allograft nephropathy or glomerulonephritis (n = 25); 3 - late acute rejection (n = 12); 4 - chronic CsA nephrotoxicity (n = 18). The patients of all groups had approximately the same C0 level, but CsA exposure estimated from AUC and C2 single-point sample proved to be significantly different in the groups with late acute rejection and chronic CsA nephrotoxicity compared to patients with stable graft function. AUC measurement using a limited sample strategy (LSS) (0, 1 and 3 hours postdose) has been shown to be an accurate method of estimating AUC. From the single time point measurement the best correlation with AUC was found for C3 (r2 = 0,68) and C2 (r2 = 0,65).

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