nefrНефрологияNephrology (Saint-Petersburg)1561-62742541-9439Pavlov First Saint-Petersburg State Medical University10.36485/1561-6274-2023-27-1-41-47nefr-2195Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИ (КЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯ)ORIGINAL ARTICLES (CLINICAL STUDIES AND EXPERIMENTAL STUDIESОсобенности протеомного профиля мочи у больных с первичными подоцитопатиямиUrine proteome profile in primary podocytopathieshttps://orcid.org/0000-0001-7529-0215ВиноградовА. А.VinogradovA. A.

Анатолий Александрович Виноградов, аспирант

факультет фундаментальной медицины

кафедра внутренних болезней

119991

Ломоносовский пр-т., д. 27, корп. 1

Москва

тел.: (985) 1179371

Anatoliy A. Vinogradov, Postgraduate student, MD

Faculty of Fundamental Medicine

Department of Internal Medicine

119991

Lomonosovsky pr-t., 27, bldg. 1

Moscow

anatoliy_vinogradov@list.ruhttps://orcid.org/0000-0003-2128-8560ЧеботареваН. В.ChebotarevaN. V.

Наталья Викторовна Чеботарева, проф., д-р мед. наук

клиника ревматологии, нефрологии и профпатологии имени Е. М. Тареева

кафедра внутренних, профессиональных болезней и ревматологии

119048

ул. Трубецкая, д. 8

Москва

Natalia V. Chebotareva, Prof., MD, PhD, DMedSci

Department of Internal, Occupational Diseases and Rheumatology

119048

8 Trubeckaya st.

Moscow

natasha_tcheb@mail.ruhttps://orcid.org/0000-0003-4568-7507БугроваА. Е.BugrovaA. E.

Анна Евгеньевна Бугрова, старший научный сотрудник, канд. биол. наук

лаборатория нейрохимии

119334

ул. Косыгина, д. 4

Москва

Anna E. Bugrova, Senior staff scientist, PhD

Laboratory of Neurochemistry

119334

4 Kosygina st.

Moscow

anna.bugrova@gmail.comhttps://orcid.org/0000-0003-1128-1795БржозовскийА. Г.BrzhozovskijA. G.

Александр Геннадьевич Бржозовский, научный сотрудник, канд. биол. наук

Центр наук о жизни

лаборатория масс-спектрометрии и омиксных технологий

121205

Большой бульвар, д. 30, стр. 1

Москва

Alexander G. Brzhozovskij, Staff scientist, PhD

Center of Life Sciences

Laboratory of Mass Spectrometry and Omix Technologies

121205

Bolshoy Boulevard, 30, p. 1

Moscow

agb.imbp@gmail.comhttps://orcid.org/0000-0001-6175-1076КрасноваТ. Н.KrasnovaT. N.

Татьяна Николаевна Краснова, доц., канд. мед. наук

факультет фундаментальной медицины

кафедра внутренних болезней

119991

Ломоносовский пр-т., д. 27, корп. 1

Москва

Tatyana N. Krasnova, Associate Professor, MD, PhD

Department of Internal Medicine

119991

27 Lomonosovsky Ave., build. 1

Moscow

krasnovamgu@yandex.ruhttps://orcid.org/0000-0002-7232-4640МоисеевС. В.MoiseevS. V.

Сергей Валентинович Моисеев, проф., д-р мед. наук

кафедра внутренних, профессиональных болезней и ревматологии

119048

ул. Трубецкая, д. 8

Москва

Sergey V. Moiseev, Prof., MD, PhD, DMedSci

Department of Internal, Occupational Diseases and Rheumatology

119048

8 Trubeckaya st.

Moscow

avt420034@gmail.comhttps://orcid.org/0000-0002-2238-3458КононихинА. С.KononikhinA. S.

Алексей Сергеевич Кононихин, канд. физ.-мат. наук

Центр наук о жизни

лаборатория масс-спектрометрии и омиксных технологий

121205

Большой бульвар, д. 30, стр. 1

Москва

Alexey S. Kononikhin, Senior staff scientist, PhD

Center of Life Sciences

Laboratory of Mass Spectrometry and Omix Technologies

121205

Bolshoy Boulevard, 30, p. 1

Moscow

a.kononikhin@skoltech.ruМосковский государственный университет имени М. В. ЛомоносоваРоссияLomonosov Moscow State UniversityRussian FederationПервый Московский государственный медицинский университет имени И. М. Сеченова (Сеченовский Университет)РоссияFirst Moscow State Medical University named after I. M. Sechenov (Sechenov University)Russian FederationИнститут биохимической физики имени Н. М. ЭмануэляРоссияInstitute of Biochemical Physics RAS named after N. M. EmanuelRussian FederationСколковский институт науки и технологииРоссияSkolkovo Institute of Science and TechnologyRussian Federation2023070320232714147Copyright © Виноградов А.А., Чеботарева Н.В., Бугрова А.Е., Бржозовский А.Г., Краснова Т.Н., Моисеев С.В., Кононихин А.С., 20232023Виноградов А.А., Чеботарева Н.В., Бугрова А.Е., Бржозовский А.Г., Краснова Т.Н., Моисеев С.В., Кононихин А.С.Vinogradov A.A., Chebotareva N.V., Bugrova A.E., Brzhozovskij A.G., Krasnova T.N., Moiseev S.V., Kononikhin A.S.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/2195   ВВЕДЕНИЕ

   ВВЕДЕНИЕ. Первичный фокальный сегментарный гломерулосклероз (ФСГС), наряду с мембранозной нефропатией (МН), представляют собой заболевания с первичным повреждением подоцитов, проявляющиеся высокой протеинурией и нефротическим синдромом. В то время как при первичной МН механизмы достаточно хорошо изучены, патогенез первичного ФСГС до настоящего времени неизвестен, в связи с чем актуальной задачей является поиск биомаркеров, которые могли бы расширить наши представления о его патогенетических механизмах.

   ЦЕЛЬ

   ЦЕЛЬ: определить особенности протеомного профиля мочи пациентов с первичными подоцитопатиями – ФСГС в сравнении с МН.

   ПАЦИЕНТЫ И МЕТОДЫ

   ПАЦИЕНТЫ И МЕТОДЫ. В исследование включены 48 пациентов с морфологически подтвержденным диагнозом ХГН, протекающего с нефротическим синдромом – 32 мужчины и 16 женщин. У 18 пациентов наблюдалось снижение скорости клубочковой фильтрации < 60 мл/мин/1,73 м2. Всем пациентам проведена биопсия почки и верифицирован морфологический диагноз: 31 пациент – ФСГС, в качестве группы сравнения включено 17 больных с МН. Исследование протеома мочи проводилось методом высокоэффективной жидкостной хроматографии / масс-спектрометрии.   РЕЗУЛЬТАТЫ. У больных ФСГС по сравнению с группой МН было отмечено повышенное содержание 22 различных белков, наиболее значимыми являлись апо-липопротеин А-I, гемопексин, витронектин, фактор роста пигментного эпителия, компоненты системы комплемента (С3, С4b, факторы В и Н), ретинол- и витамин D-связывающие белки, альфа-2-HS-гликопротеин, богатый гистидином гликопротеин, плазменный протеазный ингибитор С1. При МН была выявлена повышенная экскреция с мочой С2 компонента комплемента, альфа-цепи фибриногена, остеопонтина и SH3-связывающего домена протеина 3, богатого глутаминовой кислотой.   ЗАКЛЮЧЕНИЕ. Протеомный профиль мочи при ФСГС в отличие от МН отражает активацию одновременно нескольких патологических процессов – повреждения подоцита, вовлечение париетальных эпителиальных клеток, тубулоинтерстициального повреждения и накопления экстрацеллюлярного матрикса. Также отмечена активация комплемента по альтернативному и классическому пути.

   BACKGROUND

   BACKGROUND. Primary focal segmental glomerulosclerosis (FSGS) and membranous nephropathy (MN) are diseases with primary podocyte damage with high proteinuria and nephrotic syndrome. While the mechanisms in primary MN are well understood, the pathogenesis of primary FSGS is still unknown, and therefore, the search for biomarkers that could expand ourunderstanding of its pathogenetic mechanisms.

   THE AIM

   THE AIM: to determine the urine proteomic profile of patients with primary podocytopathies – FSGS in comparison with MN.

   PATIENTS AND METHODS

   PATIENTS AND METHODS. The study included 48 patients with a morphologically confirmed diagnosis of CGN occurring with nephrotic syndrome – 32 men and 16 women. In 18 patients, a decrease in glomerular filtration rate < 60 ml/min/1.73 m2 was observed. The histological diagnosis was confirmed by biopsy: 31 patients had FSGS, 17 patients with MN were included as a comparison group. The study of the urinary proteome was carried out by high performance liquid chromatography/mass spectrometry. RESULTS. In patients with FSGS, compared with the MN group, an increased content of 22 different proteins was noted, the most abundant were apolipoprotein A-I, hemopexin, vitronectin, pigment epithelial growth factor, components of the complement system (C3, C4b, factors B and H), retinol – and vitamin D-binding proteins, alpha-2-HS-glycoprotein, histidine-rich glycoprotein, plasma C1 protease inhibitor. In MN, increased urinary excretion of the complement component C2, fibrinogen alpha chain, osteopontin, and the SH3 domain-binding glutamic acid-rich-like protein 3, was detected.

   CONCLUSION

   CONCLUSION. The proteomic profile of urine in FSGS, compared to MN, reflects the activation of variety of pathological processes – podocyte damage, involvement of parietal epithelial cells, tubulo-interstitial damage, accumulation of extracellular matrix, and complement activation process.

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