Glomerular Capillary Microaneurysms in Membranoproliferative Glomerulonephritis: A Clinicopathological Study Highlighting the Involvement of IgG3

ABSTRACT

Glomerular capillary microaneurysm (GCM) is a pathological lesion defined by aneurysmal dilatation of glomerular capillaries resulting from mesangiolysis with severe endothelial damage and is commonly observed in diabetic nephropathy and thrombotic microangiopathy. However, its clinicopathological significance in membranoproliferative glomerulonephritis (MPGN)‐pattern glomerular diseases remains unclear. We retrospectively reviewed 50 renal biopsy cases diagnosed as MPGN or MPGN‐like glomerulopathy and identified 12 GCM‐positive cases for clinicopathological analysis, including Pathologische Anatomie Leiden Endothelium (PAL‐E) staining and CD34 immunohistochemistry to assess endothelial injury. Among GCM‐positive cases, proliferative glomerulonephritis with monoclonal immunoglobulin G deposits (PGNMID) was significantly enriched; however, exclusive glomerular IgG3 positivity was consistently observed across other diagnostic categories, irrespective of light‐chain restriction. Electron microscopy revealed continuous, irregularly shaped, fine granular subendothelial electron‐dense materials with endothelial denudation. PAL‐E staining was positive in all evaluable cases, with ultrastructurally identified diaphragmed endothelial fenestrae. Furthermore, CD34 staining demonstrated loss of continuous lining in GCM lesions, suggesting severe endothelial injury. Clinically, all patients presented with nephrotic‐range proteinuria, and more than half progressed to end‐stage kidney disease or died within 3 years. These findings indicate that GCM‐positive MPGN‐pattern glomerular diseases represent an aggressive subset associated with IgG3‐dominant deposition and severe endothelial injury, with important diagnostic implications.