Pathogenesis and Treatment of Idiopathic Membranous Nephropathy

Idiopathic membranous nephropathy (IMN) is among the leading causes of primary glomerular kidney disease and nephrotic syndrome in adults. Meanwhile, it significantly contributes to the incidence of end-stage renal disease. The complex and unique pathogenesis of IMN poses significant challenges to clinical treatments. The growing research evidence suggests a correlation between phospholipase A2 receptor (PLA2R) antibody levels and disease activity in IMN, while thrombospondin type 1 domain containing 7A (THSD7A) also plays a key role in its pathogenesis. However, the reciprocal regulatory relationship between these target antigens and IMN is yet to be explored, thereby preventing the implementation of targeted therapies as the definitive treatment. In recent years, advances in understanding IMN immunopathogenesis have facilitated the development of targeted immunotherapies, particularly B cell-directed agents such as rituximab. These therapies have demonstrated promising clinical efficacy, with significant reductions in proteinuria and delayed disease progression in a subset of patients. However, treatment resistance, relapses, and adverse events remain prevalent, limiting the widespread adoption of these therapies. This review aims to provide a comprehensive overview of the current understanding of IMN, including its pathogenic mechanisms, clinical features, differential diagnosis, and therapeutic strategies rooted in disease biology. Particular emphasis is placed on balancing efficacy with safety to inform the development of more precise and individualized treatment approaches.