nefrНефрологияNephrology (Saint-Petersburg)1561-62742541-9439Pavlov First Saint-Petersburg State Medical University10.36485/1561-6274-2021-25-4-11-22nefr-2004Research ArticleОБЗОРЫ И ЛЕКЦИИREVIEWS AND LECTURESНефропротективное действие новых сахароснижающих препаратов: глифлозиныNephroprotective effect of novel oral sugar-reducing medicines: glyflosinshttps://orcid.org/0000-0002-8101-103XЗверевЯ. Ф.ZverevYa. F.

Проф. Зверев Яков Федорович, д-р мед. наук, кафедра фармакологии, профессор

656038, г. Барнаул, пр. Ленина, д. 40

Тел.: (3852)566891

Prof. Yakov F. Zverev MD, DMedSci, Department of Pharmacology

656038, Barnaul, Lenin avenue, 40

Phone: (3852)566-891

zveryasha@mail.ruhttps://orcid.org/0000-0002-5889-7071РыкуноваА. Я.RykunovaA. Ya.

Рыкунова Анна Яковлевна, канд. мед. наук, кафедра криминалистики, старший преподаватель

656038, г. Барнаул, ул. Чкалова, д. 49

Тел.: (3852)379163

Anna Ya. Rykunova, Department of Criminology

656038, Barnaul, Chkalov st., 49

Phone: (3852)379163

zveranna@mail.ruАлтайский государственный медицинский университетРоссияAltai State Medical UniversityRussian FederationБарнаульский юридический институтРоссияBarnaul Law InstituteRussian Federation2021130720212541122Copyright © Зверев Я.Ф., Рыкунова А.Я., 20212021Зверев Я.Ф., Рыкунова А.Я.Zverev Y.F., Rykunova A.Y.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.nephrolog.ru/jour/article/view/2004

Обзор посвящен рассмотрению нефропротективного действия и его механизмов у новых сахароснижающих препаратов глифлозинов, выявленных в ходе крупномасштабных рандомизированных плацебо-контролируемых испытанийи экспериментальных исследований. Выяснилось, что ингибирование натрий-глюкозного котранспортера 2 (SGLT2) в проксимальных канальцах почек при использовании этих препаратов не только приводит к уменьшению уровня глюкозы в крови, снижению артериального давления, массы тела, содержанию мочевой кислоты в плазме крови, но также задерживает прогрессирование хронической болезни почек, угнетая развитие диабетической нефропатии. Этоблагоприятный эффект является многофакторным. Он обусловлен диуретическим и натрийуретическим действием, уменьшением уровня альбуминурии, ослаблением глюкотоксичности в клетках почечных канальцев, гемодинамическим воздействием на функцию почек и прямым противовоспалительным эффектом. Обсуждается, почему при применении ингибиторов SGLT2 восстанавливается тубулогломерулярная обратная связь, нарушаемая в начальный период диабетической нефропатии и ведущая к гиперфильтрации в оставшихся нефронах. Приводятся сведения о восстановлении нарушенной функции митохондрий благодаря позитивному влиянию препаратов на ионный состав клеток почечных канальцев. Это в значительной степени способствует усилению аутофагии, опосредованного лизосомами пути деградации и удаления поврежденных органелл и нормализующей внутриклеточный гомеостаз. Рассматривается вероятный механизм усиления аутофагии через повышение активности сенсоров энергетической депривации клеток AMPK и SIRT1. Обсуждаются возможные механизмы развития противовоспалительного и антиоксидантного действия ингибиторов SGLT2 через подавление активности инфламмасомы. Рассматривается вопрос о возможном применении глифлозинов при хронической болезни почек, патогенез которой не связан с сахарным диабетом.

The review is devoted to the consideration of the nephroprotective effect and its mechanisms in new hypoglycemic drugs gliflozins, identified in largescale randomized placebo-controlled trials and experimental studies. It was found that inhibition of sodium-glucose co-transporter 2 (SGLT2) in the proximal tubules of the kidneys when using these drugs not only leads to a decrease in blood glucose levels, a decrease in blood pressure, body weight, and uric acid content in blood plasma but also delays the progression of chronic kidney disease, inhibiting the development of diabetic nephropathy. This beneficial effect is multifactorial. It is caused by the diuretic and natriuretic effects, a decrease in albuminuria, a decrease in glucotoxicity in the cells of the renal tubules, a hemodynamic effect on kidney function, and a direct anti-inflammatory effect. It is discussed why the use of SGLT2 inhibitors restores tubuloglomerular feedback, which is disrupted in the initial period of diabetic nephropathy and leads to hyperfiltration in the remaining nephrons. Information is provided on the restoration of impaired mitochon drial function due to the positive effect of drugs on the ionic composition of renal tubule cells. This greatly contributes to the enhancement of autophagy, the lysosome-mediated pathway of degradation and removal of damaged organelles, and normalizes intracellular homeostasis. The probable mechanism of autophagy enhancement through increased activity of energy deprivation sensors of AMPK and SIRT1 cells is considered. Possible mechanisms of development of anti-inflammatory and antioxidant action of SGLT2 inhibitors through inhibition of inflammasome activity are discussed. The question of the possible use of gliflozins in chronic kidney disease, the pathogenesis of which is not associated with diabetes mellitus, is considered.

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