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. 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 Rituximab Perhaps 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. It must be kept in mind, however, that each of the 5 medications also carry their own risks, on top of prednisone. The twin aims of treating membranous nephropathy are first to induce a remission of the nephrotic syndrome and second to prevent the development of end-stage kidney failure. A meta-analysis of