Membranous glomerulonephritis (MGN), also known as membranous nephropathy is a slowly progressive disease affecting mostly patients between ages of 30 and 50 years. 85% of MGN cases are classified as primary membranous glomerulonephritis -- that is to say, the cause of the disease is idiopathic (unknown). The remainder is secondary due to :

• autoimmune conditions (e.g., systemic lupus erythematosus)
• infections (e.g., syphilis, malaria, hepatitis B)
• drugs (e.g., captopril, NSAIDs)
• inorganic salts
• malignant tumors (in particular, carcinoma of the lung and colon, and melanoma)

Pathogenesis

MGN is caused by circulating immune complex. Current research indicates that the majority of the immune complexes are formed via binding of antibodies to antigens in situ to the glomerular basement membrane. The said antigens may be endogenous to the basement membrane, or "planted" from systemic circulation.

The immune complex serves as an activator that triggers a response from the C5b - C9 complements, which form a membrane attack complex (MAC) on the glomerular epithelial cells. This, in turn, stimulates release of proteases and oxidants by the mesangial and epithelial cells, damaging the capillar walls and causing it to become "leaky". In addition, the epithelial cells also seem to secrete an unknown mediator that reduce nephrin synthesis and distribution.

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Morphology

The defining point of MGN is the presence of subepithelial immunoglobulin-containing deposits along the glomerular basemement membrane. By light microscopy, the basement membrane is observed to be diffusively thickened. On electron microscopy, subepithelial deposits that nestle against the glomerular basement membrane seems to be the cause of the thickening. Also, the podocytes lose their foot processes.

As the disease progresses, the deposits will eventually be cleared, leaving cavities in the basement membrane. This will later be filed with basement membrane-like material, and if the disease continues even further, the glomeruli will become sclerosed and finally hyalinized.

Immunoflourescence microscopy will reveal typical granular deposition of immunoglobulins and complement along the basement membrane.

Clinical Course

For idiopathic cases, the start of the disease is marked by the development of nephrotic syndrome (ureanemia, proteinuria, hyperlipidemia, lipiduria). Even if nephrotic syndrome is not present, proteinuria is almost always present, due to the damage to the glomerular capillaries. The proteinuria is nonselective and does not respond to corticosteroid therapy.For