Urine proteome profile in primary podocytopathies

Abstract

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