The role of cytokines in the formation and prediction of refractory neprotic syndrome in membranous nepropathy

BACKGROUND . The lack of reliable methods for predicting the development of treatment-refractory membranous nephropathy (MNP) with nephrotic syndrome (NS) is due to a lack of understanding of the mechanisms of NS resistance to treatment.THE AIM: to study the features of the cytokine status in patients with MNP and their significance in the formation and prediction of refractory NS. PATIENTS AND METHODS . The study was prospective and included a cohort of patients with MPN who were admitted to the nephrology department with active NS and were subsequently followed up for 24 months in the nephrologist's office at the polyclinic. The study endpoint was the completion of the 24-month follow-up period, during which the study group was divided into two subgroups based on their response to treatment: a subgroup of patients with treatment-responsive NS and a subgroup of patients with treatment-refractory NS. At the beginning of treatment and after 24 months, blood and urine samples were collected to determine the levels of cytokines IL-2, IL-4, IL-8, IL-10, and IL-17A, which were stored at -70°C until analysis. The levels of cytokines were determined simultaneously using enzyme-linked immunosorbent assay at the end of treatment. RESULTS . The study included 136 patients with MNP: 98 patients with the debut of NS, 25 with persistent NS, and 13 with frequent NS relapses. After 24 months of follow-up, 78 patients were found to have NS remission. 58 patients were refractory to treatment. In patients with refractory NS, blood and urine samples showed increased baseline levels of pro-inflammatory cytokines IL-8 and IL-17A and decreased levels of IL-10 compared to those in patients who achieved disease remission. CONCLUSION . According to the results of the study, the initial normalized by creatinine levels of IL-8 and IL-17A in the urine can be used as biomarkers for early prediction of refractory NS in MPN