The underlying causes of primary FSGS and MCD remain unknown. The aim of the study is to determine a proteomic profile capable of differentiating between MCD, FSGS, and MN in patients with nephrotic syndrome. Material and methods. The study cohort consisted of 56 participants, including individuals with confirmed diagnoses of MCD (n=10), FSGS (n=22), and MN with aPLA2R positivity (n=24). All urine samples underwent duplicate analysis using Targeted quantitative LC-MS/MS employing MRM with stable isotope-labeled peptide standards. Results. In FSGS patients, we observed elevated levels of proteins associated with podocyte damage, markers of lipid metabolism, oxidation processes, various serine proteases and their inhibitors, complement components, as well as proteins indicative of tubular cell damage and tubulo-interstitial involvement. Notably, the expression of vitronectin in podocytes and RBP4 in proximal tubular cells correlated with increased urine protein excretion in FSGS. For MCD patients, we observed an increase in СD44, afamin, corticosteroid-binding globulin, and plasma serine protease inhibitor in urine samples. Conclusion. FSGS exhibits a diverse spectrum of proteins in urine. This profile suggests a high profibrogenic potential, implicating a broad range of mechanisms. These include podocyte damage, activation of epithelial-mesenchymal transformation of resident cells, complement system activation, tubulointerstitial damage, and ECM accumulation.

This non-randomized controlled study aimed to assess the efficacy of tofacitinib in reducing the risk of invasive mechanical ventilation or death in patients with COVID-19. Patients with COVID-19 associated with reduced oxygen saturation, increased C-reactive protein (≥50 mg/L), and/or persisting fever were recruited. Tofacitinib was administered in addition to standard of care therapy. Study outcomes were evaluated separately in the groups of patients with oxygen saturation at rest ≤93% and >93%. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated using Cox regression analysis adjusted for inverse propensity score weighting. Overall, 384 patients with COVID-19 (212 males; median age 60 years) were included in our study and were treated with tofactinib (n=131) or standard of care alone (n=253). The percentages of patients who started mechanical ventilation or died during hospitalization in the tofacitinib and control groups were 12.5% (9/72) vs. 14.1% (26/185) among patients who required respiratory support (HR 0.92, 95% CI 0.33-2.56), and 1.7% (1/59) vs. 4.4% (3/68) in those with normal oxygen saturation (HR 0.83; 95 CI 0.07-9.44). Tofacitinib did not reduce the risk of invasive mechanical ventilation or death in patients with COVID-19, although the analysis of these outcomes favored tofacitinib.