2.2 Crescentic glomerulonephritis and others, vasculitis

Definition: Crescentic glomerulonephritis is of variable aetiology and pathogenesis with more than 50% crescents.

Crescentic glomerulonephritis is of variable aetiology and pathogenesis with more than 50% crescents. The common feature of all forms of glomerulonephritis with crescents is necrosis of the glomerular loops, i.e. a defect of the endothelium, the basement membrane and podocytes. This leads to exudation of plasma, including fibrin, into the capsular space. Proliferation of the parietal epithelium of Bowman’s capsule is a reaction to the insudation of plasma proteins into Bowman’s capsule. The  clinical term for all forms of glomerulonephritis with rapid progressive deterioration of renal function is rapid progressive glomerulonephritis (RPGN).

Pathogenetically three forms must be differentiated. The diagnosis can only be made with the help of immunohistology:

1. Immune complex-glomerulonephritis
2. Anti-glomerular basement membrane glomerulonephritis (Anti-GBM-GN), i.e. glomerulonephritis with antibodies against antigens of the glomerular basement membrane
3. ANCA-glomerulonephritis, i.e. glomerulonephritis with anti-neutrophilic cytoplasmic antibodies

ANCA- glomerulonephritis  may be associated with drug intake.

1) Immune complex-glomerulonephritis

Any immune complex-glomerulonephritis may be associated with extracapillary crescents. In a minority  of cases crescents are present in more than 50% of the glomeruli involved. Immunohistology is essential for the definitive diagnosis of the underlying immune complex-glomerulonephritis.

2) Anti-glomerular basement membrane glomerulonephritis

The characteristic finding by immunohistology is linear staining of the peripheral glomerular basement membranes for IgG and less so for IgM and IgA. Complement C3 may be present in a short linear or granular form. This linear staining is also seen in glomeruli that are unchanged by light microscopy.

3) ANCA-glomerulonephritis

No or only slight deposits of immunoglobulins (IgM) or complement (= pauci-immune glomerulonephritis) are present. The light microscopic lesions in the glomeruli are similar to those found in Anti-GBM-glomerulonephritis.

In most cases more than 50% of the glomeruli show extracapillary crescents. Different stages of evolution of crescents are seen side by side (capillary loop necrosis, fresh fibrin exudation or global proliferation of the parietal epithelium). Initially the crescents are purely cellular (cellular crescents), later basement membrane-like material is deposited (fibro-cellular crescent) and finally, a network of collagen develops (fibrous crescent). The end result is generally complete obsolescence of the involved glomeruli. The changes in the tubulo-interstitial space parallel those in the glomeruli.

 However, ANCA-glomerulonephritis differs in four aspects from both the before mentioned glomerulonephritides: 

•  extreme focal and segmental lesions in the beginning
•  severe destruction of Bowman’s capsule often with  granulamatous periglomerulitis with a few giant cells
•  interstitial inflammatory infiltrate often containing many plasma cells
• vasculitis in 10-20%