2.1 Epimembranous Glomerulonephritis

Definition: GN with immune deposits on the outside of the basement membrane without mesangial proliferation

Four different stages of evolution and regression of GN can be differentiated.

In stage I the glomeruli appear often normal by light microscopy. High power magnification shows at best a slight thickening of the peripheral basement membranes, which are covered by enlarged and hypertrophic, basophilic podocytes. In Trichome stains, minute protein deposits may be identified on the outside of some, but by no means all basement membranes.

In stage II the basement membranes are clearly thickened. Silver staining reveals typical spikes i.e. radial comb-like protrusions on the outside of the basement membranes. Spikes consist of newly formed basement membrane material in-between the protein deposits. The spikes vary in size, depending upon the dimensions of the protein deposits. Even at this stage the diagnosis may be missed by light microscopy.

In stage III, the protein (electron dense) deposits become completely covered by newly formed basement membrane, so that they are effectively situated within the basement membrane. The entire basement membrane is markedly thickened, but the original basement membrane is often thinner, due to continuous degradation on the inside.

In stage IV, the thickness of the basement membrane becomes highly irregular. In stages III and IV more and more global or segmental obsolescent glomeruli are found.

In all stages, but more often in advanced stages, foam cells in tubules and interstitium are present. With increasing glomerular damage, especially glomerular obsolescence, tubular atrophy and interstitial fibrosis develop.

By immunohistology, the protein deposits contain IgG and C5b-9, less often IgM, C3, C4, and C1q. In children and in drug-induced membranous GN, the deposits may be focal and segmental, but usually they are global and diffuse.

Although the classification suggests an inevitable progression from stage I to stage IV, the disease may go into spontaneous remission at any stage. In secondary forms, e.g. due to drugs, infections (hepatitis B), tumors etc. causal therapy may promote rapid remission of the disease.

In case remission takes place in stage I or early in stage II, by electron microscopy complete normalization of the basement membrane may be seen within one year.