The importance of detection of autoantibodies to podocytes in primary podocytopathies

Primary podocytopathies, minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are diseases with unknown pathogenesis. Currently, it is assumed that the production of autoantibodies to podocyte antigens is the cause of damage to the glomerular barrier and the development of nephrotic syndrome in these kidney diseases. Aim. To determine the value of detecting antibodies to podocyte nephrin and synaptopodin for the diagnosis of MCD and FSGS. Materials and methods. The study included 75 patients with nephrotic syndrome: 38 were diagnosed with FSGS, 12 with MCD, and 25 with membranous nephropathy. Samples from 11 healthy individuals were obtained as a control group. The level of antibodies to nephrin and synaptopodin in the blood serum of patients and healthy individuals was determined by enzyme immunoassay. Results. Serum antibody levels in patients with MCD and FSGS were significantly higher than in patients with membranous nephropathy and in healthy individuals. An increase in antibodies to nephrin compared to healthy individuals was found in 91% of patients with MCD and 69% of patients with FSGS, antibodies to synaptopodin were increased in 92% of patients with MCD and 73% of patients with FSGS, however, no significant difference was found in the average level of these antibodies between the MCD and FSGS groups. According to ROC-analysis, the serum nephrin antibody level over 41.6 ng/ml had a high specificity of 80% but a low sensitivity of 56.1% for diagnosing podocytopathies. Higher values were calculated for synaptopodin antibodies (sensitivity 78.12%, specificity 90.48% for a level of 10.2 ng/ml). Simultaneous assessment of nephrin and synaptopodin antibodies significantly increased the diagnostic accuracy for determining MCD/FSGS: sensitivity was 85.7%, specificity 90.48%, AUC 0.935 (95% CI 0.856–0.984). Conclusion. The level of nephrin and synaptopodin antibodies increases in patients with MCD and FSGS compared to membranous nephropathy and healthy individuals. Combined assessment of antibodies to nephrin and synaptopodin allows to increase the accuracy of diagnostics of primary podocytopathies.