AJKD Atlas of Renal Pathology: Glomerulonephritis With Dominant C3

Abstract

Glomerulonephritis with dominant C3, a form of C3 glomerulopathy, typically presents with subnephrotic proteinuria and hematuria. Although a minority of patients may present with nephrotic syndrome, about half present with hypertension and impaired glomerular filtration rate. Up to 15% progress to end-stage renal disease. C3 glomerulopathy is rare with a typical age of onset of 30 years (range, 7-70 years). Light microscopy: Most biopsies show a membranoproliferative pattern. Other less common histologic patterns include mesangial proliferative, diffuse endocapillary hypercellularity, and crescentic. Immunofluorescence microscopy: Dominant or only C3 mesangial and capillary loop staining, at least 2+ stronger than immunoglobulin and C1q staining. Electron microscopy: Mesangial and subendothelial deposits with occasional subepithelial deposits, possibly hump-like, without dense transformation of the deposits. Abnormalities in alternative complement pathway regulation, genetic or acquired. Dense deposit disease can present with similar light microscopy and immunofluorescence findings, but has diagnostic ribbon-like dense deposits within the glomerular basement membrane, not seen in this form of C3 glomerulopathy. Postinfectious glomerulonephritis can present with a similar pattern of C3 dominant staining by immunofluorescence; however, endocapillary hypercellularity with numerous neutrophils and subepithelial hump-like deposits revealed by electron microscopy are features that help distinguish it from glomerulonephritis with dominant C3. Some patients with pathologic features indistinguishable from typical postinfectious glomerulonephritis have an atypical prolonged clinical course, and may have underlying complement dysregulation, indicative of a C3 glomerulopathy. •Only C3 or dominant C3 staining, 2+ greater than immunoglobulin or C1q shown by immunofluorescence•No dense transformation of the glomerular basement membranes revealed by electron microscopyFigure 2Glomerulonephritis with dominant C3 showing contour duplication of glomerular basement membranes (Jones silver stain).View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 3Glomerulonephritis with dominant C3, with strong mesangial and capillary wall C3 staining (immunofluorescence microscopy, C3).View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 4Glomerulonephritis with dominant C3, with subendothelial deposits associated with interposed cell (asterisk) and new basement membrane material between the interposed cell and endothelium (arrow; electron microscopy).View Large Image Figure ViewerDownload Hi-res image Download (PPT)