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 such as ACE inhibitors or angiotensin II receptor blockers. Given spontaneous remission is common, international guidelines recommend a period of watchful waiting before considering immunosuppressive treatment. Likelihood of achieving spontaneous remission is much higher if anti-proteinuric therapy with ace inhibitors or angiotensin II receptor blockers is commenced.Recommended first line immunosuppressive therapy often includes: cyclophosphamide alternating with a corticosteroid, also known as the Ponticelli regime. Immunosuppressive therapy options
Corticosteroids: They have been tried with mixed results, with one study showing prevention of progression to kidney failure without improvement in proteinuria. Chlorambucil
Cyclosporine
Tacrolimus
Cyclophosphamide
Mycophenolate mofetil
RituximabPerhaps the most difficult aspect of membranous glomerulonephritis is deciding which people to treat with immunosuppressive therapy as opposed to simple "background" or anti-proteinuric therapies. A large part of this difficulty is due to a lack of ability to predict which people will progress to end-stage kidney disease, or kidney disease severe enough to require dialysis. Because the above medications carry risk, treatment should not be initiated without careful consideration as to risk/benefit profile. Of note, corticosteroids (typically Prednisone) alone are of little benefit. They should be combined with one of the other 5 medications, each of which, along with prednisone, has shown some benefit in slowing down progression of membranous nephropathy.
This, in turn, stimulates release of proteases and oxidants by the mesangial and epithelial cells, damaging the capillary walls and causing them to become "leaky". In addition, the epithelial cells also seem to secrete an unknown mediator that reduces nephrin synthesis and distribution.Within membranous glomerulonephritis, especially in cases caused by viral hepatitis, serum C3 levels are low.Similar to other causes of nephrotic syndrome (e.g., focal segmental glomerulosclerosis or minimal change disease), membranous nephropathy is known to predispose affected individuals to develop blood clots such as pulmonary emboli. Membranous nephropathy in particular is known to increase this risk more than other causes of nephrotic syndrome though the reason for this is not yet clear. Morphology
The defining point of MGN is the presence of subepithelial immunoglobulin-containing deposits along the glomerular basement membrane (GBM). By light microscopy, the basement membrane is observed to be diffusely thickened. Using Jones stain, the GBM appears to have a "spiked" or "holey" appearance. 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. These cavities will later be filled with basement membrane-like material, and if the disease continues even further, the glomeruli will become sclerosed and finally hyalinized. Immunofluorescence microscopy will reveal typical granular deposition of immunoglobulins and complement along the basement membrane.Although it usually affects the entire glomerulus, it can affect parts of the glomerulus in some cases.