Diagnosis of C3G
A diagnosis of C3 Glomerulopathy (C3G) requires a renal biopsy and careful review of light microscopy, immunofluorescence and electron microscopy. Broadly, C3G is defined as the predominant staining of C3 on immunofluorescence (IF) when compared to immunoglobulin (intensity >2 orders of magnitude). C3G is classified by electron microscopy findings into dense deposit disease or C3 Glomerulonephritis, depending on the presence or absence of dense osmiophilic intramembranous deposits.
Light microscopy identifies diverse patterns of glomerular injury that include MPGN, and detect additional features such as crescentic disease or markers of chronic disease such as interstitial fibrosis and tubular atrophy.
C3 glomerulonephritis (C3GN) is a form of C3G in which the dense osmiophilic intramembranous deposits that define DDD are not identified on electron microscopy. Appearances on EM include light dense, amorphous mesangial, paramesangial, sub-endothelial and sub-epithelial deposits. The IF criterion used to classify C3G captures the majority of cases of C3GN. Light microscopy identifies a diverse pattern of glomerular injury that includes MPGN, mesangial hypercellularity and proliferative glomerulonephritis.
Dense Deposit Disease
Dense deposit disease (DDD) is a specific form of C3G that is classified by the presence of dense osmiophilic intramembranous deposits seen on electron microscopy. The IF criterion used to classify C3G captures ~ 90% of DDD cases.
Historically, DDD was classified as a form of MPGN (Type 2). However, diverse patterns of glomerular injury have been identified in DDD that also includes mild mesangial hypercellularity, crescentic glomerulonephritis or an acute proliferative and exudative pattern. An MPGN pattern of injury is observed in only 25% of DDD cases.