Membranous Glomerulonephritis

Immune complexes (black) are deposited in a thickened basement membrane
creating a "spike and dome" appearance on electron microscopy.

MGN, or membranous nephropathy as it is sometimes called, accounts for approximately 30% of cases of nephrotic syndrome in adults, with a peak incidence between the ages of 30–50 years and a male to female ratio of 2:1. It is rare in childhood and by far the most common cause of nephrotic syndrome in the elderly.
In 25–30% of cases, MGN is secondary to
malignancy (solid tumors of the breast, lung, colon),
infection (hepatitis B, malaria, schistosomiasis), or
rheumatologic disorders like lupus or rarely rheumatoid arthritis

Primary/idiopathic membranous glomerulonephritis
Secondary membranous glomerulonephritis
  Infection: Hepatitis B and C, syphilis, malaria, schistosomiasis, leprosy, filariasis
  Cancer: Breast, colon, lung, stomach, kidney, esophagus, neuroblastoma
  Drugs: gold, mercury, penicillamine, nonsteroidal anti-inflammatory agents, probenecid
  Autoimmune diseases: systemic lupus erythematosus, rheumatoid arthritis, primary biliary cirrhosis, dermatitis herpetiformis, bullous pemphigoid, myasthenia gravis, Sjögren's syndrome, Hashimoto's thyroiditis
  Other systemic diseases: Fanconi's syndrome, sickle cell anemia, diabetes, Crohn's disease, sarcoidosis, Guillain-Barré syndrome, Weber-Christian disease, angiofollicular lymph node hyperplasia

Uniform thickening of the basement membrane along the peripheral capillary loops is seen by light microscopy on renal biopsy ; this thickening needs to be distinguished from that seen in diabetes and amyloidosis. Immunofluorescence demonstrates diffuse granular deposits of IgG and C3, and electron microscopy typically reveals electron-dense subepithelial deposits.

While different stages (I–V) of progressive membranous lesions have been described, some published analyses indicate the degree of tubular atrophy or interstitial fibrosis is more predictive of progression than is the stage of glomerular disease. The presence of subendothelial deposits or the presence of tubuloreticular inclusions strongly points to a diagnosis of membranous lupus nephritis, which may precede the extrarenal manifestations of lupus. Work in Heyman nephritis, an animal model of MGN, suggests that glomerular lesions result from in situ formation of immune complexes with megalin receptor–associated protein as the putative antigen. This antigen is not found in human podocytes, but human antibodies have been described against neutral endopeptidase expressed by podocytes, hepatitis antigens B/C, Helicobacterpylori antigens, tumor antigens, and thyroglobulin.

Eighty percent of patients with MGN present with nephrotic syndrome and nonselective proteinuria. Microscopic hematuria is seen in up to 50% of patients. Spontaneous remissions occur in 20–33% of patients and often occur late in the course after years of nephrotic syndrome. One-third of patients continue to have relapsing nephrotic syndrome but maintain normal renal function, and approximately another third of patients develop renal failure or die from the complications of nephrotic syndrome.
Male gender, older age, hypertension, and the persistence of proteinuria are associated with worse prognosis. Although thrombotic complications are a feature of all nephrotic syndromes, MGN has the highest reported incidences of renal vein thrombosis, pulmonary embolism, and deep vein thrombosis. Prophylactic anticoagulation is controversial but has been recommended for patients with severe or prolonged proteinuria in the absence of risk factors for bleeding.

In addition to the treatment of edema, dyslipidemia, and hypertension, inhibition of the renin-angiotensin system is recommended. Therapy with immunosuppressive drugs is also recommended for patients with primary MGN and persistent proteinuria (>3.0 g/24 h). The choice of immunosuppressive drugs for therapy is controversial, but current recommendations based on small clinical studies are to treat with steroids and cyclophosphamide, chlorambucil, or cyclosporine. Experience with mycophenolate mofetil or anti-CD20 antibody is even more limited.