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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.

One of the most prognostically unfavorable variants of glomerulopathy is focal segmental glomerulosclerosis (FSHC), which is detected by nephrobiopsy in 5-20% of patients with nephrotic syndrome (NS) and in 15% of adult patients with chronic glomerulonephritis. FSGS recurs in a transplanted kidney in 30-50% of patients. Among adult patients with FSH, men predominate. A poor prognosis of FSHC is explained by the heterogeneity of the disease and is exacerbated by a poor response to treatment. According to current data, FSGS is characterized by sclerosis of the mesangial matrix, hyalinosis, damage to capillaries, an increase in foam cells and their adhesion between the glomerular bundle and the Bowman capsule. In 2004, the following histological variants of FSGS were proposed: apical, perichillary, collaborating, cellular and classical. Each histological variant of FSGS differs in etiology, response to treatment, and prognosis. The clinical diagnosis of primary FSHC should be based on the exclusion of secondary causes of the disease. Focal sclerotic changes in the glomeruli can be caused by various factors and occur in various conditions, including the existing kidney pathology. According to international recommendations for the treatment of FSHS, one should focus on the amount of daily proteinuria. For patients with FSHS without pronounced proteinuria, the use of angiotensin converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor blockers (ARBs) is recommended. In FSGS and NS, immunosuppressive therapy is used along with ACE inhibitors or ARB II. For adult patients, glucocorticoids (HA) are prescribed daily in a single dose at a dose of 1 mg / kg per day, the maximum dose is 80 mg with a daily intake and 120 mg with an alternating regimen. Resistance to HA is detected in the absence of effect after 16 weeks. In the presence of contraindications or intolerance to HA, calcineurin inhibitors are used. The recommended initial dose of cyclosporine is 2 mg / kg / day, taken twice a day with a gradual increase to 3.5-4 mg / kg / day. The duration of therapy with satisfactory tolerance to cyclosporine is more than six months. After achieving complete remission, the dose of cyclosporin is gradually reduced by 0.5 mg / kg / day to the minimum effective dose (1.5-2 mg / kg / day) and such maintenance therapy is carried out for 1-2 years. A treatment option is possible using lower doses of HA and cyclosporine, or a combination of mycophenolate mofetil with a high dose of dexamethasone.

We present a case with a rare variant of glomerulonephritis, IgM nephropathy, which occurs mainly with nephrotic syndrome. The clinical features of this variant of kidney damage are characterized; the pathogenetic and the transformation of this form of nephritis into focal segmental glomerulosclerosis are discussed. The development of severe nephrotic syndrome at the beginning of the disease, the formation of secondary steroid resistance have confirmed this hypothesis and have justified the treatment with cyclosporin A aimed at the recovery of the function of the podocyte with remission of nephritis.

Objective: An evaluation of podocyte's molecular phenotype alterations in primary focal segmental glomerulosclerosis (pFSGS) and IgA nephropathy (IgAN)., Material and Methods: The exploratory study included 14 cases of morphologically confirmed pFSGS, 14 cases of IgAN, and 12 negative controls. The negative controls comprised samples of the unaltered renal cortex obtained during laparoscopic nephrectomy in patients with malignant neoplasms of the kidney and bladder and without proteinuria. A quantitative immunomorphological study of Wilms tumour protein (WT1) expression and mesenchymal markers of podocytes (desmin and vimentin) was conducted on all kidney samples. The co-expression of the aforementioned molecules was analysed using confocal microscopy., Results: Cases of pFSGS exhibited nephrotic syndrome with proteinuria of 9.3 (3.1-14) g/24 and typical glomerular alterations in light microscopy and ultrastructural analysis. In the IgAN group, proteinuria was less severe (1.2 (0.7-1.6) g/24). The estimated glomerular filtration rate in pFSGS and IgAN was similar (pFSGS: 85 (53-103) ml/min/1.72 m², IgAN: 76 (52-87) ml/min/1.72 m²; p =0.40). In both pFSGS and IgAN, there was a reduction in WT1 expression in podocytes and an increase in vimentin expression when compared to negative controls. Compared to IgAN and controls, pFSGS exhibited a lower prevalence of glomerular WT1 expression and higher expression of desmin, which was predominantly localised in WT1-negative glomerular areas in confocal microscopy. In pFSGS, decreased nuclear expression of WT1 and increased expression of desmin were observed in the parietal epithelium of the glomerular capsule., Conclusion: Bidirectional alterations in the glomerular expression of WT1 and intermediate filament proteins are apparent in pFSGS and IgAN. These findings are suggestive for the genomic reprogramming of podocytes and the parietal epithelium of the glomerulus as part of the epithelial-mesenchymal transition, determining the structural and functional disorders of these cells, more prominent in pFSGS.

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.

We present a case with a rare variant of glomerulonephritis, IgM nephropathy, which occurs mainly with nephrotic syndrome. The clinical features of this variant of kidney damage are characterized; the pathogenetic and the transformation of this form of nephritis into focal segmental glomerulosclerosis are discussed. The development of severe nephrotic syndrome at the beginning of the disease, the formation of secondary steroid resistance have confirmed this hypothesis and have justified the treatment with cyclosporin A aimed at the recovery of the function of the podocyte with remission of nephritis.

The review presents the results of recent experimental and clinical studies of the expression pattern of a number of miRNAs, a recently described new class of noncoding RNAS that are able to regulate the posttranscriptional expression of genes and thus to modulate several physiological and pathological processes in different morphological types of chronic glomerulonephritis. It considers the possibilities of using miRNAs as new biomarkers to diagnose the disease, to predict its course and a response to therapy.