Поражение почек, ассоциированное с противоопухолевой терапией: фокус на нежелательные явления современных иммуноонкологических препаратов

Камышова Е.С., Бобкова И.Н., Секачева М.И. Поражение почек, ассоциированное с противоопухолевой терапией: фокус на нежелательные явления современных иммуноонкологических препаратов. Терапевтический архив. 2021; 93 (6): 649–660. DOI: 10.26442/00403660.2021.06.200860

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Kamyshova ES, Bobkova IN, Sekacheva MI. Kidney injury associated with antitumor therapy: focus on the adverse events of modern immuno-oncological drugs. Terapevticheskii Arkhiv (Ter. Arkh). 2021; 93 (6): 649–660.
DOI: 10.26442/00403660.2021.06.200860

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Аннотация

Ингибиторы иммунных контрольных точек (ИКТ), в том числе антиген цитотоксических Т-лимфоцитов 4 (cytotoxic T-lymphocyte antigen 4 –
CTLA-4), рецептор запрограммированной гибели 1 (programmed death 1 – PD-1) и его лиганд 1 (PD-ligand-1 – PD-L1), представляют собой иммуноонкологические препараты нового поколения, которые к настоящему времени продемонстрировали эффективность при ряде злокачественных новообразований. Механизм действия ингибиторов ИКТ заключается в потенцировании иммунного отчета за счет устранения тормозящего влияния опухолевых клеток на активацию Т-лимфоцитов. Однако чрезмерная активация иммунной системы может стать причиной развития особого класса иммуноопосредованных нежелательных явлений (иоНЯ) со стороны ряда органов и систем, в том числе почек. Несмотря на то, что иммуноопосредованное поражение почек на фоне терапии ингибиторами ИКТ развивается относительно редко, оно может быть серьезным и определять прогноз пациента, что обусловливает необходимость ранней диагностики и своевременного начала лечения. В связи с этим приобретает особую актуальность информированность о проявлениях иоНЯ со стороны почек на фоне иммунотерапии не только онкологов и нефрологов, но и врачей других специальностей. В настоящем обзоре описаны основные варианты иммуноопосредованного поражения почек, обусловленного терапией ингибиторами ИКТ, обсуждены возможные предикторы и механизмы их развития, рассмотрены общие принципы диагностики и ведения пациентов с учетом степени тяжести иоНЯ.

Ключевые слова: ингибиторы иммунных контрольных точек, антиген цитотоксических Т-лимфоцитов 4, рецептор запрограммированной гибели 1, лиганд рецептора запрограммированной гибели 1, иммуноопосредованные нежелательные явления со стороны почек

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Immune checkpoint inhibitors (ICIs), including cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) and programmed death protein 1 (PD-1) or its ligand (PD-L1), are a new generation of immuno-oncological drugs that to date have demonstrated efficacy in a number of malignancies. The mechanism of ICT inhibitors action consist in the potentiation of the immune response by eliminating the tumor cells inhibitory effect on the T-lymphocytes activation. However, excessive immune system activation can cause the development of a special class of immune-related adverse events (irAEs) involved a wide variety of organs and systems, including the kidneys. Despite the fact that immuno-mediated kidney injury caused by ICI therapy develops quite rarely, it can be serious and determine the patient's prognosis, which necessitates early diagnosis and timely start of treatment. In this regard, awareness of the manifestations of ICI-associated renal irAEs is particularly relevant not only for oncologists and for nephrologists, but for doctors of other specialties. In this review, we elucidated the main variants of immuno-mediated kidney injury caused by ICI therapy, discussed possible predictors and mechanisms of their development, and considers the general principles of diagnosis and management of patients according to the severity of irAEs.

Keywords: immune checkpoint inhibitors, cytotoxic T-lymphocyte associated antigen 4, programmed death protein 1, programmed cell death 1 ligand 1, renal immune-related adverse events

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DOI:10.2215/CJN.06480612

Авторы

Е.С. Камышова*, И.Н. Бобкова, М.И. Секачева

ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет), Москва, Россия
*kamyshova-es@yandex.ru

________________________________________________

Elena S. Kamyshova*, Irina N. Bobkova, Marina I. Sekacheva

Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
*kamyshova-es@yandex.ru

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