safetyriskБезопасность и риск фармакотерапииSafety and Risk of Pharmacotherapy2312-78212619-1164Federal State Budgetary Institution ‘Scientific Centre for Expert Evaluation of Medicinal Products’ of the Ministry of Health of the Russian Federation (FSBI ‘SCEEMP’)10.30895/2312-7821-2020-8-3-123-133safetyrisk-185Research ArticleОБЗОРЫREVIEWSНекоторые аспекты оценки лекарственного поражения почекSome Aspects of Drug Induced Nephrotoxicity Assessmenthttps://orcid.org/0000-0002-6389-2099СоковаЕ. А.SokovaE. A.

канд. мед. наук, доцент

Петровский б-р, д. 8, стр. 2, Москва, 127051

Трубецкая ул., д. 8, стр. 2, Москва, 119991

Cand. Sci. (Med.), Associate Professor

8/2 Petrovsky Blvd, Moscow 127051

8/2 Trubetskaya St., Moscow 119991

sokova904@gmail.comhttps://orcid.org/0000-0002-1441-3418АрхиповВ. В.ArkhipovV. V.

 д-р. мед. наук, доцент

Петровский б-р, д. 8, стр. 2, Москва, 127051

Dr. Sci. (Med.), Associate Professor

8/2 Petrovsky Blvd, Moscow 127051

arkhipov@expmed.ruhttps://orcid.org/0000-0002-3733-6822МазеркинаИ. А.MazerkinaI. A.

канд. мед. наук

Петровский б-р, д. 8, стр. 2, Москва, 127051

Cand. Sci. (Med.)

8/2 Petrovsky Blvd, Moscow 127051

mazerkina@expmed.ruhttps://orcid.org/0000-0003-1009-9609МуслимоваО. В.MuslimovaO. V.

канд. мед. наук

Петровский б-р, д. 8, стр. 2, Москва, 127051

Cand. Sci. (Med.)

8/2 Petrovsky Blvd, Moscow 127051

muslimova@expmed.ruФедеральное государственное бюджетное учреждение «Научный центр экспертизы средств медицинского применения» Министерства здравоохранения Российской Федерации; Федеральное государственное автономное образовательное учреждение высшего образования «Первый Московский государственный университет им. И.М. Сеченова» Министерства здравоохранения Российской ФедерацииРоссияScientific Centre for Expert Evaluation of Medicinal Products, I. M. Sechenov First Moscow State Medical UniversityRussian FederationФедеральное государственное бюджетное учреждение «Научный центр экспертизы средств медицинского применения» Министерства здравоохранения Российской ФедерацииРоссияScientific Centre for Expert Evaluation of Medicinal ProductsRussian FederationФедеральное государственное бюджетное учреждение «Научный центр экспертизы средств медицинского применения» Министерства здравоохранения Российской ФедерацииРоссияScientific Centre for Expert Evaluation of Medicinal ProductsRussian Federation20200408202083123133Copyright © Сокова Е.А., Архипов В.В., Мазеркина И.А., Муслимова О.В., 20202020Сокова Е.А., Архипов В.В., Мазеркина И.А., Муслимова О.В.Sokova E.A., Arkhipov V.V., Mazerkina I.A., Muslimova O.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.risksafety.ru/jour/article/view/185

От 14 до 26% лекарственных средств, применяемых в клинической практике, являются потенциально нефротоксичными, оставаясь частой причиной развития острого повреждения почек и хронической болезни почек. Острое повреждение почек у взрослых и детей ассоциировано с высоким риском повторных госпитализаций, осложнений и летальных исходов. Цель работы: анализ научной информации о современных подходах к оценке лекарственного поражения почек. Описаны патогенетические механизмы повреждения почек при применении лекарственных препаратов, а также молекулярные механизмы повреждения, индуцированного приемом лекарственных средств на уровне их транспортеров. Рассмотрены факторы риска развития лекарственного поражения почек: возраст, пол, этническая принадлежность, коморбидные состояния (хроническая болезнь почек, сахарный диабет, сердечно-сосудистые заболевания, иммунные расстройства, сепсис и др.), доза и продолжительность терапии, фармакокинетика лекарственных средств, взаимодействие потенциально нефротоксичных препаратов, генетическая детерминированность метаболизма и транспорта лекарственных средств и другие. Показано, что традиционные маркеры нефротоксичности — уровень креатинина и величина диуреза — обладают низкой чувствительностью в определении ранней стадии повреждения почек, поэтому продолжается поиск новых почечных биомаркеров для диагностики и мониторинга острого повреждения почек у пациентов с различными заболеваниями. Некоторые из этих биомаркеров уже применяются при разработке новых лекарственных средств, в доклинических, клинических исследованиях для оценки и прогнозирования безопасности препаратов. Проведенный анализ показал, что ни один из новых почечных биомаркеров не является универсальным для рутинного использования в клинической практике. Разработка новых биомаркеров острого повреждения почек является долгосрочной инвестицией и необходима для ранней диагностики и успешного лечения лекарственного поражения почек.

About 14‒23% of all clinically used drugs have nephrotoxic potential and are a frequent cause of acute and chronic kidney problems. Acute kidney injury (AKI) is associated with a high risk of repeat hospitalisation, complications, and mortality in adults and children. The aim of the study was to provide an overview of the current approaches to the assessment of drug induced nephrotoxicity. The paper summarises pathogenetic mechanisms of drug induced kidney injury as well as molecular mechanisms at the drug transporters level. It analyses risk factors for drug induced kidney injury—age, sex, ethnicity, comorbidities (chronic kidney disease, diabetes, cardiovascular disease, immune disorders, sepsis, etc.), drug dosage and duration of therapy, pharmacokinetics of drugs, combinations of potentially nephrotoxic drugs, genetic determinants of drug metabolism and transport, etc. It was demonstrated that the traditional nephrotoxicity markers—serum creatinine and urine output—have low sensitivity as indicators of early renal damage. Therefore, new kidney biomarkers are being sought for in order to be used in AKI diagnosis and monitoring in patients with different comorbidities. Some of these biomarkers are already used in drug development, preclinical and clinical trials for assessment and prediction of drug safety. The analysis showed that none of these new kidney biomarkers could be used as an all-purpose tool in routine clinical practice. The development of new AKI biomarkers is a long-range objective and is the path toward early diagnosis and successful treatment of drug-induced nephrotoxicity.

лекарственное средствоострое повреждение почеклекарственное поражение почекбиомаркеры острого почечного повреждениятранспортеры лекарственных средствdrugacute kidney injurydrug induced kidney injurybiomarkers of acute kidney injurydrug transportersРабота выполнена в рамках государственного задания ФГБУ «НЦЭСМП» Минздрава России № 056-00003-20-00 на проведение прикладных научных исследований (номер государственного учета НИР AAAA-A18-118021590047-6)The study reported in this publication was carried out as part of a publicly funded research project No. 056-00003-20-00 and was supported by the Scientific Centre for Expert Evaluation of Medicinal Products (R&D public accounting No. AAAA-A18-118021590047-6)ReferencesAwdishu L, Mehta RL. The 6R’s of drug induced nephrotoxicity. BMC Nephrol. 2017;18(1):124. https://doi.org/10.1186/s12882-017-0536-3Awdishu L, Mehta RL. The 6R’s of drug induced nephrotoxicity. 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The authors declare that there are no conflicts of interest present.