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[Study of urinary markers of different podocytopathies by proteomic analysis]. [通过蛋白质组分析研究不同荚膜细胞病的尿液标记物]。
IF 0.3 Q2 Mathematics Pub Date : 2023-08-17 DOI: 10.26442/00403660.2023.06.202266
A A Vinogradov, N V Chebotareva, A E Bugrova, A G Brzhozovskiy, T N Krasnova, K Z Nasibullina, A S Kononikhin, S V Moiseev

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.

背景:局灶节段性肾小球硬化症(FSGS)是一种原发性荚膜细胞病变,以原发性荚膜细胞检测和高蛋白尿为特征。目的:评估 FSGS 患者尿液的蛋白质组谱,并分离出荚膜细胞病变的尿液生物标志物:研究对象包括41名被诊断为慢性肾小球肾炎的患者,其中男性27名,女性14名。根据形态学研究,28 名患者被诊断为 FSGS,9 名患者被诊断为类固醇敏感性肾病综合征,14 名患者被诊断为类固醇耐受性肾病综合征。对比组包括 13 名膜性肾病患者。尿液蛋白质组的研究采用了靶向液相色谱-质谱法,使用合成的稳定同位素标记肽标准进行多重反应监测:结果:在类固醇敏感(SS)和类固醇耐受(SR)FSGS亚组中发现了尿液蛋白质谱的主要差异。在FSGS SR组中,发病初期尿液中含有大量反映肾小球滤过膜损伤的蛋白质(载脂蛋白A-IV、osomucoid、cadherin、hemopexin、vitronectin),以及与肾小管间质炎症和细胞外基质堆积有关的蛋白质(视黄醇和维生素D结合蛋白、激肽原-1、lumican和neurophilin-2)。与膜性肾病组相比,FSGS 患者尿液中肌肽酶、瘤胃球蛋白、粘连蛋白-13、腱鞘蛋白 X、骨通蛋白和锌α-2-糖蛋白的浓度明显更高:因此,与 SS FSGS 和膜性肾病患者相比,SR FSGS 患者的尿液蛋白质组谱中有更多的蛋白质浓度升高,这反映了肾小球各部分的严重损伤。
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