nidНефрология и диализNephrology and Dialysis1680-44222618-9801Российское диализное обществоnid-819Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESМорфологические особенности позднего отторжения трансплантированной почки и их влияние на течение и прогноз нефропатииLate kidney allograft rejection: the impact of pathology on the long-term outcomeСтоляревичЕ. С.StolyarevichE. S.stolyarevich@yandex.ruАртюхинаЛ. Ю.ArtyuhinaL. Y.noemail@neicon.ruКимИ. Г.KimI. G.noemail@neicon.ruКуренковаЛ. Г.KurenkovaL. G.noemail@neicon.ruТомилинаН. А.TomilinaN. A.noemail@neicon.ruФГУ «ФНЦ Трансплантологии и искусственных органов им. академика В.И. Шумакова» МЗ и СР РФ; Кафедра нефрологии ФПДО МГМСУРоссияV.I. Shumakov Federal Scientific Center of Transplantology and artificial organs of Russian Health Ministry, Moscow; Department of Nephrology, Moscow Medical-dental UniversityRussian FederationГКБ № 52 г. МоскваРоссияMoscow City hospital No 52Russian FederationФГУ «ФНЦ Трансплантологии и искусственных органов им. академика В.И. Шумакова» МЗ и СР РФРоссияV.I. Shumakov Federal Scientific Center of Transplantology and artificial organs of Russian Health Ministry, MoscowRussian FederationФГУ «ФНЦ Трансплантологии и искусственных органов им. академика В.И. Шумакова» МЗ и СР РФ; Кафедра нефрологии ФПДО МГМСУ; ГКБ № 52 г. МоскваРоссияV.I. Shumakov Federal Scientific Center of Transplantology and artificial organs of Russian Health Ministry, Moscow; Department of Nephrology, Moscow Medical-dental University; Moscow City hospital No 52Russian Federation201217062025144242252Copyright © Столяревич Е.С., Артюхина Л.Ю., Ким И.Г., Куренкова Л.Г., Томилина Н.А., 20252025Столяревич Е.С., Артюхина Л.Ю., Ким И.Г., Куренкова Л.Г., Томилина Н.А.Stolyarevich E.S., Artyuhina L.Y., Kim I.G., Kurenkova L.G., 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/819

Отторжение трансплантата остается одной из наиболее частых причин дисфункции почечного трансплантата в поздние сроки после АТП. Целью настоящего исследования было проанализировать частоту встречаемости различных вариантов позднего отторжения трансплантата, выявить особенности их клинических проявлений и течения, а также определить морфологические и клинические факторы, определяющие прогноз нефропатии при различных типах позднего отторжения трансплантата. Проанализированы материалы 265 пациентов, которым в связи с поздней дисфункцией почечного трансплантата было выполнено 294 биопсии (в среднем через 48,8 ± 46,1 мес. после АТП), на основании чего верифицирован диагноз острого (n = 194) или хронического (n = 78) отторжения трансплантата либо (в 22 случаях) их сочетание. Свечение C4d выявлялось в 34% случаев острого отторжения и в 59% случаев при ХОТ (в том числе при ХТГ – 65%, при васкулопатии – 50%). 5-летняя выживаемость трансплантатов составила 48, 34 и 17% при ООТ, ХОТ и сочетании ООТ+ХОТ соответственно (p < 0,01). При этом в случаях острого отторжения прогноз C4d+ форм был хуже, чем в отсутствие свечения C4d (53% v s 33%; p = 0,002), тогда как при хроническом отторжении подобная закономерность отсутствовала (36% vs 34%; p = NS). В многофакторной модели Кокса прогностическое значение имели ХТГ, признаки васкулита, распространенность интерстициального фиброза и плазмаклеточный характер инфильтрата. Из клинических факторов наибольшее прогностическое значение имела выраженность дисфункции трансплантата: повышение креатинина крови на каждые 0,1 ммоль/л увеличивает вероятность неблагоприятного исхода отторжения на 60%. В зависимости от исходного Pcr (<0,2; 0,2–0,3; 0,3–0,4; >0,4 ммоль/л) 2-летняя выживаемость трансплантата при остром отторжении составляла 97,5; 78,5; 67,8 и 20,7%, тогда как при ХОТ эти показатели составили 75; 33,9; 20,8 и 0% соответственно, то есть при уровне креатинина более 0,2 ммоль/л, у большинства пациентов с ХОТ рецидив терминальной ХПН развивался уже в первые 2 года с момента диагностики отторжения, что определяет необходимость максимально ранней диагностики и лечения этой патологии.

Rejection has always been one of the most important cause of late renal graft dysfunction. The aim of the study was to analyze the prevalence of different clinical and pathological variants of rejection that cause late graft dysfunction and to evaluate their impact on long-term outcome. A retrospective study included 294 needle core biopsy specimens from 265 renal transplant recipients with late (48,8 ± 46,1 months after transplantation) allograft dysfunction caused by late acute rejection (LAR n = 194) or chronic rejection (CR n = 78) or both (n = 22). C4d staining was performed by immunofluorescence (IF) on frozen sections using a standard protocol. Peritubular capillary C4d deposition was identified in 34% samples with acute rejection and in 59% cases of chronic rejection (65% cases of transplant glomerulopathy, and 50% of isolated chronic vasculopathy). 5-year graft survival for LAR vs CR vs combination were 48%, 34% и 17%, respectively. The outcome of C4d+ LAR was better (p < 0,01) than of C4d+ acute rejection: at 60 months, graft survival for diffuse C4d+ vs focal C4d+ vs C4d– were 29% vs 51% vs 43%, respectively. In cases of chronic rejection C4d+ vs C4d– was not statistically significant (34% vs 36%). By multivariate Cox analysis the risk of graft loss was associated with transplant glomerulopathy, intimal arteriitis, widespread interstitial fibrosis and plasma cell-rich infiltrates. Among clinical factors serum creatinine had a strongest impact on graft outcome: using Cox regression, the hazard ratio of graft loss was 1,6 (1,42–1,79) for each 0,1 mmol/l (p = 0,017). 5-year graft survival according to the initial serum creatinine were 97,5; 78,5; 67,8 and 20,7% for <0,2; 0,2–0,3; 0,3–0,4; >0,4 mmol/l respectively for LAR and 75; 33,9; 20,8 and 0% for CR. Proteinuria >3 g/d was a poor prognostic factor for LAR. No statistically significant difference was found for proteinuria vs mild to moderate urine protein level. In contrast for CR recipients only the absence of proteinuria had a significant positive impact on graft outcome compared with mild moderate or heavy proteinuria.

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