Membranoproliferative Glomerulonephritis

Membranoproliferative glomerulonephritis (MPGN) is not one disease with one cause. It is a histopathologic pattern showing how the glomerulus has been injured. The pattern usually includes mesangial and endocapillary proliferation, capillary-wall remodelling, and duplication or “double contouring” of the glomerular basement membrane. On light microscopy, the duplicated membrane can produce a tram-track appearance. The classification is now pathogenesis-driven. Immunofluorescence separates the pattern into: - Immune-complex-mediated MPGN: immunoglobulins and complement are deposited in the glomerulus. Common drivers include hepatitis B or C, chronic bacterial infection such as endocarditis, systemic lupus erythematosus, cryoglobulinaemia, and monoclonal gammopathy. - Complement-mediated disease, usually called C3 glomerulopathy: C3 deposition predominates because regulation of the alternative complement pathway is impaired. C3 nephritic factor or inherited abnormalities in complement-regulatory proteins may contribute. The biopsy pattern includes C3 glomerulonephritis and dense-deposit disease. - Immunoglobulin- and complement-negative MPGN: little or no immune staining is present, so the clinician must reconsider other causes of a proliferative or membranous-appearing glomerular lesion. The filtration barrier is damaged from two directions. Inflammation and capillary-wall remodelling narrow the glomerular capillary loops and reduce filtration, while...