Membranous glomerulonephritis

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 capillary 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.

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 Presentation

Some patients may present as nephrotic syndrome with proteinuria, edema with or without renal failure. Others may be asymptomatic and may be picked up on screening or urinalysis as having proteinuria. A definitive diagnosis of membranous nephropathy requires a kidney biopsy.

Treatment

Treatment of secondary membranous nephropathy is guided by the treatment of the original disease. For treatment of idiopathic membranous nephropathy, the treatment options include immunosuppressive drugs and non-specific anti-proteinuric measures.

Immunosuppressive therapy

Corticosteroids: They have been tried with mixed results, with one study showing prevention of progression to renal failure without improvement in proteinuria.
Chlorambucil
Cyclophosphamide
Mycophenolate mofetil

Natural History

About a third of patients have spontaneous remission, another third progress to require dialysis and the last third continue to have proteinuria, without progression of renal failure.

Inflammations