Clinicopathological Features of Membranoproliferative Glomerulonephritis with Glomerular Capillary Microaneurysms

Background: Glomerular capillary microaneurysms (GCMs) are aneurysmal dilatations of capillary loops, thought to result from focal mesangiolysis. While frequently seen in diabetic nephropathy, thrombotic microangiopathy (TMA), and monoclonal immunoglobulin deposition disease (MIDD), they are rarely reported in other glomerular diseases. This study aimed to clarify the clinicopathological characteristics of MPGN-pattern glomerular diseases with GCMs. Methods: Among adult kidney biopsies performed at Nippon Medical School between 2011 and 2024, 62 were pathologically diagnosed as MPGN or MPGN-like glomerulopathy. After excluding cases with comorbid diabetes mellitus or TMA, 49 cases were analyzed. Of these, 12 with GCMs were selected for detailed clinicopathological evaluation. Results: Among the 49 MPGN cases, the most common etiologies were cryoglobulinemic GN (CryoGN), hepatic IgA nephropathy (hepatic IgAN), and proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID). In contrast, among the 12 GCM (+) cases, 5 were PGNMID (IgG3κ or λ), followed by CryoGN (n = 2), C3 glomerulopathy (n = 1), immunotactoid glomerulopathy (n = 1), PGN with polyclonal IgG3 deposits (n = 1), and unknown etiology (n = 2). The proportion of GCM (+) cases was significantly higher in PGNMID than in hepatic IgAN (p = 0.003) and CryoGN (p = 0.04). Immunofluorescence revealed immunoglobulin and complement deposition in 10 of 12 cases. Notably, all 8 cases assessed for IgG subclasses showed monotypic IgG3 deposition, and light chain restriction was confirmed in 5 of 10. PAL-E staining was positive in glomeruli, indicating endothelial injury. Electron microscopy showed endothelial denudation, subendothelial widening, and fibrin exudation. Deposits included non-organized (n = 7), organized (n = 5), and powdery types along glomerular capillary walls, resembling those seen in MIDD. Clinically, the mean age, proteinuria, and serum creatinine among the 12 cases were 61.7 years, 8.6 g/gCr, and 2.5 mg/dL, respectively. Over half progressed to end-stage kidney disease or death within 3 years, indicating poor prognosis. Conclusion: MPGN with GCMs is frequently associated with PGNMID and shows marked glomerular endothelial injury. GCMs may serve as a morphological marker of severe endothelial damage and may be linked to pathogenic IgG3 deposition. Funding: Government Support – Non-U.S.