Association between Anti-Nephrin Antibodies and Podocytopathies: A Systematic Review and Meta-Analysis

The aim of the study was to explore the positive rate of anti-nephrin antibodies in various podocytopathies and their relationship with the clinical characteristics and outcomes of podocytopathies.

Medical literature studies from the PubMed database and the Web of science database from the establishment of the databases to July 28, 2025, were retrieved online. The main exploration indicator is the positive rate of anti-nephrin antibody in podocytopathies. Other indicators include the diagnostic role of anti-nephrin antibodies and their relationship with the clinical features and outcomes of podocytopathies. Analysis was conducted using the R software package "Meta" and "Mada."

A meta-analysis included a total of 1,567 patients from 15 studies. The positive rates of anti-nephrin antibodies in adult patients with primary podocytopathies, minimal change disease, primary focal segmental glomerulosclerosis (FSGS), and children with idiopathic nephrotic syndrome (NS) were 41%, 51%, 32%, and 39%, respectively. Anti-nephrin antibodies are almost undetectable in patients with secondary FSGS, membranous nephropathy and other glomerular diseases. In podocytopathies with nephrotic-range proteinuria or without the use of immunosuppressants, the positive rate increased. The sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of anti-nephrin antibody in differentiating steroid-sensitive NS (SSNS) from non-SSNS in children were 0.57, 0.83, 3.40, and 0.55, respectively. Patients positive for anti-nephrin antibody had higher urinary protein levels and lower serum albumin levels and were more prone to recurrence, but there were no statistically significant differences in gender, age, renal function, and remission rate. The heterogeneity of the positive rate results of anti-nephrin antibodies in the literature is very high (I2 >80%), and most subgroup analyses cannot explore the source of the heterogeneity.

Anti-nephrin antibodies have a relatively high positive rate in podocytopathies and have a differentiating effect on SSNS and non-SSNS in children. Anti-nephrin antibodies are associated with the clinical severity and recurrence of podocytopathies.