Membranous  glomerulonephritis (MGN) is a form of kidney disease associated with heavy proteinuria and the depletion of plasma proteins, distinguished by the seeming lack of inflammation that is characteristic of other types of glomerulonephritis (Janeway et al. 1999). It is the most common form of nephrotic syndrome in adults (Ulrich 1996), 25% to 50% of whom eventually progress to end stage renal failure (Davenport et al. 1994). The disease is considered idiopathic if it has no know cause; this strain is predominant in adult males of thirty to fifty years (Wasserstein 1997). The secondary strain of membranous glomerulonephritis makes up the cases in 25% of adults and 80% of children, associated worldwide primarily with malaria and schistomiasis, but some of the main precursors in the U.S. are systemic lupus erythematosus and hepatitis B (Wasserstein 1997). Generic precursors include nuclear antigens, immunoglobulin, bacteria, viruses, fungi, parasites and drugs or other toxic agents (Delves 1998).

      The main characteristic of MGN is the thickening of the glomerular basement membrane with subepithelial immune deposits (Ulrich 1996). While the scientific community debates whether it is an autoimmune disorder, extensive studies in rats with Heymann nephritis (thought to be MGNís counterpart), further suggest that it is cause by immune deposits from undigested complement complexes (Janeway et al. 1999). The course of the disease may begin with the formation of IgG antibodies, which bind to glycoprotein antigens (in mice gp330) found in pits of the glomerular epithelial cells. These immune complexes then shed into the glomerular basement membrane, where they activate a complement cascade. The terminal complement cascade (C5b-9) is deposited along the glomerular capillary wall, where it can be transported across the epithelial cells into the urinary space (Honkanen et al. 1994). Although there may be some initial repair of the basement membrane, new subepithelial deposits result in a relapse to MGN (Ulrich 1996).  It is possible that the immune complexes are deposited when something prevents the association of C3b to the complexes or the erythrocyte fails to shuttle the complement to take care of the immune complexes; they persist in circulation and become lodged in the kidney (Delves et al. 1998).
     Factors influencing the deposition of immune complexes in the glomerular basement membrane include the size of the complex, the affinity of antibody binding, defective phagocytosis or complement binding, the biochemical properties of antigen or antibody, and the hemodynamic flow (Delves et al. 1998). The high pressure of plasma at the capillary walls in the glomerulus may facilitate deposition (Delves et al. 1998). MGN is usually caused by small complexes resulting from antigen excess and low antibody affinity (Delves et al. 1998). Although inflammatory cytokines may be produced in the complement cascade, the absence of inflammation is probably due to the nature of the basement membrane, which prevents the extravasation of the leukocytes into the tissue (Janeway et al. 1999).

    It is unknown what causes idiopathic membranous glomerulonephritis and no therapy has proven effective at curing it (Bennet and Plum 1996). Evidence of CD40-CD40L/ gp39 signaling in MGN suggests that scientists might find treatment in the inhibition of the IgG co-stimulatory pathway early in the formation of immune complexes, since it is thought that IgG cross-linking with antigen allows the complexes to persist in the sub-epithelial region of the glomerulus (Biancone et al. 1995). Researchers have found that MGN does not occur in nude mice, suggesting that T-cells are necessary for its activation (Biancone et al. 1995). It appears that the prognosis is more favorable for those who have the secondary form of the disease, due to such means as infection or drug exposure (Davenport et al. 1994). Treatment for membranous glomerulonephritis presently includes corticosteroids and other immunosuppressive drugs, such as cyclosporin, which binds to calcineurin in signal transduction and blocks the activation of NF-AT and transcription (Janeway et al. 1999), as well as anticoagulants and antiplatelets to minimize glomerular damage from coagulation (Bennett and Plum 1996).

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