Evolution of immunoglobulin deposition in C3-dominant membranoproliferative glomerulopathy

Background: Complement 3 glomerulopathy (C3GN) is a newly proposed subcategory of glomerular disease with features including membranoproliferative glomerulonephritis (MPGN), C3-dominant immunofluorescent staining without appreciable immunoglobulin deposition, and electron-dense deposits. Aberrations of alternative complement pathway (AP) have been found in many C3GN patients. Case-diagnosis/treatment: A 13-year-old boy presented with edema in association with an upper respiratory infection. Studies demonstrated nephrotic syndrome with hematuria and markedly low C3 and C4. Initial renal biopsy showed MPGN with strong C3 and immunoglobulin deposition. The patient partially responded to immunosuppression. Follow-up biopsies at 10 months and 3 years demonstrated MPGN with strong C3, with little to no immunoglobulin deposition. Based on this and elevated SC5b-9, treatment was changed to eculizumab with further decrease in proteinuria. Conclusions: Serial biopsies illustrated marked variability in immunoglobulin deposition in MPGN with persistently strong C3 deposition. Whether this evolution was related to the course of disease or to therapeutic intervention, the pathologic progression documented in this series of biopsies challenges the newly proposed subcategories of MPGN.