IgM nephropathy is a controversial entity: a distinct nephropathy or part of the podocytopathy spectrum? A systematic review of the literature

Immunoglobulin M nephropathy (IgMN) has traditionally been defined by dominant mesangial IgM staining, but its significance remains debated. IgM deposition may be non-specific, diagnostic thresholds are inconsistently applied, and clinical patterns largely overlap with minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS), questioning whether IgMN constitutes a distinct entity or part of the podocytopathy spectrum. We conducted a PubMed literature review using the terms “IgM nephropathy,” “IgMN,” and “Immunoglobulin M nephropathy,”. A total of 49 individual cases have been identified in scientific literature, but only 22 cases were confirmed adopting a widely accepted definition of IgM Nephropathy: the presence of a dominant, diffuse, global mesangial IgM deposits (≥ 2 + compared with other immunofluorescence stainings) in nonsclerotic areas, supported by the presence of electron-dense deposits in the mesangial and paramesangial areas at electron microscopy. These cases underscore the heterogeneous presentation of IgMN, from steroid-resistant nephrotic syndrome to stable non-nephrotic proteinuria. Its relationship to MCD and the occasional progression to FSGS highlight the dynamic nature of IgM nephropathy as a clinico-pathological entity. A major interpretive gap is inconsistent EM incorporation; fewer than half of reported cases met strict ultrastructural criteria. Current evidence favors positioning IgMN along the podocytopathy spectrum rather than as an independent entity. Standardized diagnostic criteria integrating routine ultrastructural validation, individualized management based on clinical phenotype, and molecular biomarker identification are warranted. Prospective multicenter studies are needed to clarify the pathogenic significance of mesangial IgM and guide evidence-based therapy.