Vinogradov A A, Chebotareva N V, Bugrova A E, Brzhozovskiy A G, Krasnova T N, Nasibullina K Z, Kononikhin A S, Moiseev S V
Lomonosov Moscow State University.
Sechenov First Moscow State Medical University (Sechenov University).
Ter Arkh. 2023 Aug 17;95(6):457-461. doi: 10.26442/00403660.2023.06.202266.
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.
To assess the proteomic profile of urine in patients with FSGS and to isolate urinary biomarkers of podocytopathies.
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.
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.
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.
局灶节段性肾小球硬化（FSGS）是一种以原发性足细胞病变和高蛋白尿为特征的原发性足细胞病。寻找与该疾病进展相关的生物标志物和因素是当今一项重要任务。
评估FSGS患者尿液的蛋白质组学特征，并分离足细胞病的尿液生物标志物。
该研究纳入41例诊断为慢性肾小球肾炎的患者，其中男性27例，女性14例。根据形态学研究，28例患者诊断为FSGS，9例为激素敏感型肾病综合征，14例为激素抵抗型肾病综合征。对照组包括13例膜性肾病患者。采用靶向液相色谱-质谱联用技术，通过多反应监测结合合成稳定同位素标记肽标准品对尿液蛋白质组进行研究。
尿液蛋白质谱的主要差异存在于激素敏感型（SS）和激素抵抗型（SR）FSGS亚组中。在FSGS SR组疾病初期，反映肾小球滤过损伤的蛋白质（载脂蛋白A-IV、orosomucoid、钙黏蛋白、血红素结合蛋白、玻连蛋白）以及与肾小管间质炎症和细胞外基质积聚相关的蛋白质（视黄醇和维生素D结合蛋白、激肽原-1、纤连蛋白和神经纤毛蛋白-2）浓度较高。与膜性肾病组相比，FSGS患者尿液中肌肽酶、orosomucoid、钙黏蛋白-13、腱生蛋白X、骨桥蛋白和锌-α-2-糖蛋白的浓度显著更高。
因此，与SS FSGS患者和膜性肾病患者相比，SR FSGS患者尿液的蛋白质组学特征包括更多浓度升高的蛋白质，这反映了肾单位各部分的严重损伤。
