Study of urinary markers of different podocytopathies by proteomic analysis

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Abstract

Background. Focal segmental glomerulosclerosis (FSGS) is a primary podocytopathy characterized by primary podocyte detection and high proteinuria. The search for biomarkers and factors associated with the progression of this disease is an important task nowdays.

Aim. To assess the proteomic profile of urine in patients with FSGS and to isolate urinary biomarkers of podocytopathies.

Materials and methods. The study included 41 patients diagnosed with chronic glomerulonephritis, 27 men and 14 women. According to the morphological study, 28 patients were diagnosed with FSGS, 9 with steroid-sensitive nephrotic syndrome and 14 with steroid-resistant nephrotic syndrome. The comparison group included 13 patients with membranous nephropathy. The study of the urinary proteome was carried out by targeted liquid chromatography-mass spectrometry using multiple reaction monitoring with synthetic stable isotope labelled peptide standards.

Results. The main differences in the protein profile of urine were found in the subgroups of steroid-sensitive (SS) and steroid-resistant (SR) FSGS. In the FSGS SR group, at the onset of the disease, there was a high concentration of proteins reflecting damage to the glomerular filter (apo-lipoprotein A-IV, orosomucoid, cadherin, hemopexin, vitronectin), as well as proteins associated with tubulo-interstitial inflammation and accumulation of extracellular matrix (retinol- and vitamin D-binding proteins, kininogen-1, lumican and neurophilin-2). Compared with the membranous nephropathy group, FSGS patients had significantly higher urinary concentrations of carnosinase, orosomucoid, cadherin-13, tenascin X, osteopontin, and zinc-alpha-2-glycoprotein.

Conclusion. Thus, in patients with SR FSGS, the proteomic profile of urine includes more proteins at elevated concentrations, which reflects severe damage to various parts of the nephron compared with patients with SS FSGS and membranous nephropathy.

About the authors

Anatoliy A. Vinogradov

Lomonosov Moscow State University

Author for correspondence.
Email: anatoliy_vinogradov@list.ru
ORCID iD: 0000-0001-7529-0215

аспирант каф. внутренних болезней фак-та фундаментальной медицины ФГБОУ ВО «МГУ им. М.В. Ломоносова»

Russian Federation, Moscow

Natalia V. Chebotareva

Sechenov First Moscow State Medical University (Sechenov University)

Email: anatoliy_vinogradov@list.ru
ORCID iD: 0000-0003-2128-8560

д-р мед. наук, проф. каф. внутренних, профессиональных болезней и ревматологии ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова» (Сеченовский Университет)

Russian Federation, Moscow

Anna E. Bugrova

Emanuel Institute for Biochemical Physics

Email: anatoliy_vinogradov@list.ru
ORCID iD: 0000-0003-4568-7507

канд. биол. наук, ст. науч. сотр. лаб. нейрохимии ФГБУН «ИБХФ им. Н.М. Эмануэля»

Russian Federation, Moscow

Alexander G. Brzhozovskiy

Skolkovo Institute of Science and Technology

Email: anatoliy_vinogradov@list.ru
ORCID iD: 0000-0003-1128-1795

канд. биол. наук, науч. сотр. лаб. масс-спектрометрии и омиксных технологий Центра наук о жизни АНОО ВО «Сколтех»

Russian Federation, Moscow

Tatiana N. Krasnova

Lomonosov Moscow State University; Sechenov First Moscow State Medical University (Sechenov University)

Email: anatoliy_vinogradov@list.ru
ORCID iD: 0000-0002-7647-3942

канд. мед. наук, зав. каф. внутренних болезней фак-та фундаментальной медицины ФГБОУ ВО «МГУ им. М.В. Ломоносова», доц. каф. внутренних болезней ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова» (Сеченовский Университет)

Russian Federation, Moscow; Moscow

Karina Z. Nasibullina

Sechenov First Moscow State Medical University (Sechenov University)

Email: anatoliy_vinogradov@list.ru

студентка ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова» (Сеченовский Университет)

Russian Federation, Moscow

Alexey S. Kononikhin

Skolkovo Institute of Science and Technology

Email: anatoliy_vinogradov@list.ru
ORCID iD: 0000-0002-2238-3458

канд. физ.-мат. наук, ст. науч. сотр. лаб. масс-спектрометрии и омиксных технологий Центра наук о жизни АНОО ВО «Сколтех»

Russian Federation, Moscow

Sergey V. Moiseev

Sechenov First Moscow State Medical University (Sechenov University)

Email: anatoliy_vinogradov@list.ru
ORCID iD: 0000-0002-7232-4640

чл.-кор. РАН, д-р мед. наук, проф., зав. каф. внутренних, профессиональных болезней и ревматологии, дир. Клиники ревматологии, нефрологии и профпатологии им. Е.М. Тареева Университетской клинической больницы №3 ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова» (Сеченовский Университет)

Russian Federation, Moscow

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