nefrНефрологияNephrology (Saint-Petersburg)1561-62742541-9439Pavlov First Saint-Petersburg State Medical University10.36485/1561-6274-2022-26-4-80-88nefr-2164Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИ. КЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯORIGINAL ARTICLES. CLINICAL INVESTIGATIONSФакторы протеолиза в крови и моче как прогностические маркеры прогрессирования синдрома Альпорта у детейFactors of proteolysis in blood and urine as prognostic markers of progression of Alport syndrome in childrenhttps://orcid.org/0000-0003-3915-8617БашироваЗ. Р.BashirovaZ. R.

Баширова Зиля Рамилевна

отдел наследственных и приобретенных болезней почек имени профессора М.С. Игнатовой

125412

ул. Талдомская, д. 2

Москва

Zilya R. Bashirova

Department of Hereditary and Acquired Kidney Disease named after Professor M.S.Ignatova.

125412

st. Taldomskaya, 2

Moscow

Z-Bash@mail.ruhttps://orcid.org/0000-0003-3181-9601ОсмановИ. М.OsmanovI. M.

Османов Исмаил Магомедтагирович, проф. д-р мед. наук

125373

ул. Героев Панфиловцев, д. 28

Москва

Ismail M. Osmanov, Prof.

125373

Geroyev panfi lovtsev street, 28

Moscow

dgkb-bashlyaevoy@zdrav.mos.ruИсследовательский клинический институт педиатрии имени академика Ю.Е. Вельтищева, Российский национальный исследовательский медицинский университет имени Н. И. ПироговаРоссияVeltischev Research And Clinical Institute For Pediatrics Of The Pirogov Russian National Research Medical UniversityRussian FederationДетская городская клиническая больница имени З.А. БашляевойРоссияMoscow state budgetary healthcare institution "Children's City Clinical Hospital named after Z.A. Bashlyaeva"Russian Federation2022241120222648088Copyright © Баширова З.Р., Османов И.М., 20222022Баширова З.Р., Османов И.М.Bashirova Z.R., Osmanov I.M.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/2164

ВВЕДЕНИЕ. Синдром Альпорта – редкое наследственное заболевание почек, проявляющееся прогрессирующей почечной недостаточностью. Между пациентами с синдромом Альпорта существуют значительные различия в прогрессировании заболевания. Выявление пациентов с высоким риском быстрого прогрессирования, чтобы оптимально соотнести пользу и риск для назначения терапии, стало особенно важным в настоящее время. В этом исследовании мы хотели оценить, связаны ли факторы протеолиза в крови и моче с характером течения и оценить их прогностическое значение для детей с синдромом Альпорта. ЦЕЛЬ: определить уровень в сыворотке крови и экскрецию с мочой ММП-2, ММП-3 и ММП-9 и их ингибиторов ТИМП-1 и 2, ПАИ-I, установить связь их изменений с характером течения синдрома Альпорта у детей в качестве дополнительного критерия прогрессирования. ПАЦИЕНТЫ И МЕТОДЫ. В исследование включено 32 ребенка с синдромом Альпорта. Уровень ММП-2, ММП-3 и ММП-9 и их ингибиторов ТИМП-1 и 2, ПАИ-I в сыворотке крови и моче определяли методом ИФА. Снижение рСКФ на ≥30 % за 2 года от исходного уровня было выбрано для обозначения прогрессирующего течения синдрома Альпорта. РЕЗУЛЬТАТЫ. У 28,1 % детей с синдромом Альпорта было прогрессирующее течение заболевания, у 71,9 % – медленно прогрессирующее. Частота снижения ММП-9 и повышения ТИМП-1 как в крови (88,9 против 43,5 % и 77,8 против 21,7 %; р=0,044 и 0,006 соответственно), так и в моче (100 против 47,8 % и 88,9 против 30,4 %; 0,012 и 0,005 соответственно) статистически значимо чаще были выявлены у детей с синдромом Альпорта с прогрессирующим течением заболевания, чем при медленно прогрессирующем. ЗАКЛЮЧЕНИЕ. Полученные данные нашего исследования свидетельствуют о том, что матриксная металлопротеиназа 9-го типа и тканевый ингибитор матриксных металлопротеиназ 1 типа могут быть рассмотрены в качестве факторов риска прогрессирования синдрома Альпорта у детей.

BACKGROUND. Alport syndrome is a rare hereditary kidney disease that causes progressive renal failure. There are significant differences in the progression of the disease between patients with Alport syndrome. Identifying patients with a high risk of rapid progression in order to optimally balance benefits and risks for prescribing therapy has become particularly important at this time. In this study, we wanted to assess whether the factors of proteolysis in blood and urine are associated with the nature of the course and to assess their prognostic value for children with Alport syndrome. THE AIM: To determine the level in blood serum and urinary excretion of MMP-2, MMP-3 and MMP-9 and their inhibitors TIMP-1 and 2, PAI-I, to show the relationship of their changes with the character of the course of Alport syndrome in children as an additional criterion for progression. PATIENTS AND METHODS. The study included 32 children with Alport syndrome. The level of MMP-2, MMP-3 and MMP-9 and their inhibitors TIMP-1 and 2, PAI-I, in blood serum and urine was determined by ELISA. A decrease in eGFR of ≥ 30 % at 2 years from baseline was chosen to indicate a progressive course of Alport syndrome. RESULTS. 28.1 % of children with Alport syndrome had a progressive course of the dis ease, 71.9 % had a slowly progressive course. The frequency of a decrease in MMP-9 and an increase in TIMP-1 both in blood (88.9 versus 43.5 % and 77.8 versus 21.7 %; p = 0.044 and 0.006, respectively) and in urine (100 versus 47, 8 % and 88.9 versus 30.4 %; 0.012 and 0.005, respectively) were statistically significantly more often detected in children with Alport syndrome with a progressive course of the disease than in a slowly progressive course. CONCLUSION. Type 9 matrix metalloproteinase and type 1 tissue matrix metalloproteinase inhibitor can be considered as risk factors for the progression of Alport syndrome in children.

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