nefrНефрологияNephrology (Saint-Petersburg)1561-62742541-9439Pavlov First Saint-Petersburg State Medical University10.24884/1561-6274-2019-23-2-91-99nefr-1680Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИ. КЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯORIGINAL ARTICLES. CLINICAL INVESTIGATIONSКЛИНИКО-ПРОГНОСТИЧЕСКОЕ ЗНАЧЕНИЕ ФАКТОРОВ ПРОТЕОЛИЗА У ДЕТЕЙ С АУТОСОМНО-ДОМИНАНТНОЙ ПОЛИКИСТОЗНОЙ БОЛЕЗНЬЮ ПОЧЕКCLINICAL AND PROGNOSTIC VALUE OF PROTEOLYSIS FACTORS IN CHILDREN WITH AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASEhttps://orcid.org/0000-0003-3915-8617БашироваЗ. Р.BashirovaZ. R.

отдел наследственных и приобретенных болезней почек, научный сотрудник

MD, department of hereditary and acquired kidney disease, research assistant

Обособленное структурное подразделение «Научно-исследовательский клинический институт педиатрии им. акад. Ю.Е. Вельтищева» ФГБОУ ВО РНИМУ им. Н.И.Пирогова, отдел наследственных и приобретенных болезней почек, МоскваРоссияVeltischev Research and Clinical Institute for Pediatrics of the Pirogov Russian National Research Medical University, MoscowRussian Federation2019200220192329199Copyright © Баширова З.Р., 20192019Баширова З.Р.Bashirova Z.R.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/1680

ВВЕДЕНИЕ. Прогрессирующий почечный фиброз при различных нефропатия, в том числе при аутосомно-доминантной поликистозной болезни почек (АДПБП), является результатом дисбаланса между механизмами образования экстрацеллюлярного матрикса (ЭЦМ) и его деградации (протеолиза). Система матриксных металлопротеиназ (ММП) и их ингибиторов [тканевые ингибиторы ММП (ТИМП), ингибитор активатора плазминогена типа I – ПАИ-I] играет ключевую роль в этих процессах. В эксперименте показано, что рост кист является следствием увеличения синтеза компонентов ЭЦМ, при нарушении функционирования системы ММП/ТИМП, однако в клинических условиях эти вопросы не изучались. ЦЕЛЬ: определить экскрецию с мочой ММП-2, ММП-3 и ММП-9 и их ингибиторов ТИМП-1 и -2, ПАИ-I, установить взаимосвязь их изменений с корректированным на поверхность тела объемом почек и функциональным состоянием почек, оценить значение нарушений в системе ММП/ТИМП в качестве дополнительного критерия прогрессирования АДПБП. ПАЦИЕНТЫ И МЕТОДЫ. В исследование включены 34 ребенка с АДПБП. Уровень ММП-2, ММП-3 и ММП-9 и их ингибиторов ТИМП-1 и -2, ПАИ-I определяли в моче методом ИФА. РЕЗУЛЬТАТЫ. рСКФ у детей с суммарным объемом почек более 97 ‰ был статистически значимо более низкой, чем в группе детей с нормальным суммарным объемом почек. В группе детей с АДПБП и суммарным объемом почек более 97 ‰ выявлены статистически значимое повышение уровней ТИМП-1, ТИМП-2 и ПАИ-I в моче и достоверно более низкий уровень экскреции с мочой ММП-3 и ММП-9 по сравнению с группой детей с нормальным суммарным объемом почек. В группе детей с АДПБП и суммарным объемом почек более 97 ‰ установлена обратная корреляционная взаимосвязь между уровнем рСКФ и ТИМП-2 и ПАИ-I, а также прямая корреляционная взаимосвязь между суммарным объемом почек и мочевой экскрецией ТИМП-1. ЗАКЛЮЧЕНИЕ. ММП и их ингибиторы играют важную роль в почечном повреждении у детей с АДПБП, отражая выраженность накопления экстрацеллюлярного матрикса, что определяет перспективы их использования для мониторинга процессов фиброзирования в почке и в качестве предикторов прогрессирования АДПБП.

BACKGROUND. One of the perspectives of modern Nephrology is the study of the mechanisms of nephrosclerosis in ADPKD. Matrix metalloproteinase system (MMP/TIMP)— enzymes that play a key role in the processes of proteolysis in the kidney. THE AIM: to determine the expression of the urine MMP-2, MMP-3 and MMP-9 and their inhibitors TIMP-1 and 2, PAI-I, to establish their relationship with the volume of the kidney corrected to the surface of the body and the functional state of the kidneys, an additional criterion of progression. PATIENTS AND METHODS. The study included 34 children with ADPKD. The level of MMP-2, MMP-3 and MMP-9 and their inhibitors TIMP-1 and 2, PAI-I were determined in urine by ELISA. RESULTS. eGFR in children with total kidney volume greater than 97‰ was significantly lower than in children with normal total kidney volume. In the group of children with a total volume of the kidneys more than 97 percentile,a statistically significant increase in the level of TIMP-1 and TIMP-2 and PAI-I in the urine, and a statistically significant low level of urinary excretion of MMP-3 and MMP-9, compared with the group of children with ADPKD with normal total volume of the kidneys. In the group of children with ADPKD and total kidney volume of more than 97 percentiles of an inverse correlation relationship between the level of eGFR and TIMP-2 and PAI-I, as well as a direct correlation relationship between the total volume of kidney and the urinary excretion of TIMP-1. CONCLUSION. MMP and its inhibitors play an important role in renal damage in children with ADPKD. These proteolysis factors are promising to use as an indicator of the severity of the accumulation of extracellular matrix, that is, monitoring the process of fibrosis, and used as a predictor of progression.

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