Types of Membranoproliferative Glomerulonephritis

• Membranoproliferative Glomerulonephritis (MPGN) is one of the glomerulopahty that may lead to chronic nephritis but not very common. It mainly occurs in children and adults. The characteristic features include: proliferation of mesangial and endothelial cells and expansion of the mesangial matrix; mesangial interposition into the capillary wall, which will result in a double-contour or tram-track appearance on light microscopy; thickening of the peripheral capillary walls by subendothelial immune deposits and/or intramembranous dense deposits.

  There are mainly three types of Membranoproliferative Glomerulonephritis. Types I, II, and III are the three distinctive types of idiopathic MPGN that are described based on immunofluorescence staining, ultrastructural appearance, and complement profiles. The light microscopy features are mostly indistinguishable among the 3 types.

  Type I MPGN

  This is the most common type and the pathological changes include deposition of discrete immune in the mesangial area and subendothelial space, causing mesangial proliferation and extension into the subendothelial area. Under microscope, thickening of capillary walls can be seen, usually global and diffuse. There is also hypercellularity, much of which is mesangial proliferation, and some of the capillary wall thickening is caused by mesangial interposition into the subendothelial zone of the capillary loops.

  1. Light micrograph in Membranoproliferative Glomerulonephritis shows a lobular appearance of the glomerular tuft with focal area of increased glomerular cellularity, mesangial expansion, narrowing of the capillary lumens, and diffuse thickening of the glomerular capillary walls.

  2. Electron micrograph in type I Membranoproliferative Glomerulonephritis shows marked thichening of the glomerular capillary wall by immune deposits and by interposition of mesangial cell processes. There are two layers of the glomerular basement membrane surrounding the mesangial interposition that account for the double contour appearance on light microscopy.

  3. Immunofluorescence microscopy in Membranoproliferative Glomerulonephritis reveals complement deposition in a rim pattern outlining the glomerular capillary wall.

  Type II MPGN

  This type accounts for 15%~35% of all MPGN cases. It is characterized by a pathognomonic electron-dense transformation of glomerular basement membrane and extensive complement deposition. Immunofluorescence is positive for C3 but negative for immunoglobulins. It recurs after renal transplant over 90% cases and most have circulating IgG antibody (C3 nephritic factor) that stabilize C3bBb, C3 convertase of alternate pathway, resulted continuous C3 breakdown. In this disease, higher hypocomplementemia will have worse prognosis.

  Type III MPGN

  This type is similar to type I but subepithelial deposits are prominent and inherited form of type 3 is linked to chromosome 1q32.

  The glomerular deposits contain C3, C5, and properdin, which indicats activation of the alternative complement pathway. Signs of activation of the classic pathway are minimal, and circulating immune complexes do not appear to play a role in the genesis of this variant. 

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