How is membranoproliferative glomerulonephritis diagnosed
Although the disease may be suspected in a patient with hematuria and/or proteinuria and a reduced level of C3, a kidney biopsy is required to confirm the diagnosis.
Examination of the kidney histopathology demonstrates a lobular appearance of the glomerular tuft, mesangial expansion, hypercellularity, and the characteristic “tram track” finding with a double contour of the GBM.
Immunofluorescence staining is usually positive for C3, IgG, and IgM in a capillary wall distribution.
Classic complement cascade components are seen in type I but not types II and III MPGN.
How is membranoproliferative glomerulonephritis classified?
Primary MPGN is divided into three subtypes based on the nature and location of electron-dense deposits in addition to the expected changes in the GBM: type I, subendothelial deposits; type II, large, ribbon-like intramembranous deposits, so-called dense deposit disease (DDD); and type III, subendothelial and subepithelial deposits.
The deposits can be numerous or sparse. They are homogeneous in density and have no defining ultrastructural appearance.
The presence of C4d on immunofluorescence staining has been utilized to distinguish type I (positive) from type II (negative) MPGN.
Recently the term C3 glomerulopathy has been introduced to define cases of MPGN. It corresponds to type II MPGN (DDD) as opposed to the immune-complex–mediated forms of the disease, types I and III.
The diagnostic label MPGN is focused mainly on the light microscopy appearance (hypercellular, lobulated glomerular tuft) and the ultrastructural changes in the GBM (splitting of the GBM with mesangial cell interposition) as well as the specific location of the electron-dense deposits (subepithelial, intramembranous, or subendothelial).
In contrast, the term, C3 glomerulopathy, highlights the presence of C3 as the dominant or codominant molecule detected by immunofluorescence examination of the kidney tissue.
In this way the diagnosis sheds light on the underlying cause of the disease—activation of the alternative pathway of complement in the pathogenesis of the glomerulopathy.
Moreover, it points the way to a new therapeutic approach to MPGN and C3 glomerulopathy that reduces kidney injury by inhibiting the activity of the alternative pathway of complement