Membranous Glomerulonephritis

Overview
  • Membranous Glomerulonephritis (MGN) is a disease defined principally by a unique histopathology that primarily manifests clinically as nephrotic syndrome. It is most importantly characterized by thickening of the glomerular basement membrane together with evidence of immune complex deposition
Morphology
  • Light Microscopy
    • Diffuse thickening of the glomerular basement membrane
  • Immunofluorescence
    • Granular deposition of IgG and complement throughout the glomerular basement membrane
  • Electron Microscopy
    • Lumps of immune complex incorporated within the glomerular basement membrane lie just under the podocytes and are thus termed 'Subepithelial' deposits
    • A thin extension of the basement membrane separates each lump of immune complex, giving a collonade like pattern, sometimes referred to as a "Spike-and-dome" appearance
    • Effacement of podocyte foot processes is also frequently observed
Etiology
  • Primary Disease
    • Primary membranous glomerulonephritis appears to be an autoimmune disease
    • The current theory is that auto-antibodies are elaborated against an antigen within the glomerular barrier
    • These Auto-antibodies are thought to form 'In Situ' immune complexes, meaning the complexes are formed within the glomerular barrier and that the complex itself does not circulate (See: Basic Glomerular Pathogenesis)
    • The presence of immune complexes and their activation of complement is believed to render the glomerular barrier leaky, reducing glomerular filtration selectivity, and thus precipitating the subsequent pathogenesis of nephrotic syndrome (See page)
  • Secondary Disease
    • Membranous glomerulonephritis can appear secondary to a variety of infectious or pharmacological insults as well as in conjunction with systemic diseases
    • It should be pointed out that the pathogenesis of secondary disease is thought to be initiated by the deposition of Preformed Immune Complexes within the glomerular barrier and not 'in situ' formation (See: Basic Glomerular Pathogenesis)
    • Infectious: Hepatitis B Virus, Malaria, Treponema pallidum Infection (Syphilis)
    • Systemic Diseases: Systemic Lupus Erythematosus, Certain Malignancies
    • Toxins: Gold or mercuric chloride
    • Drugs: Penicillamine
Clinical Syndrome
  • MGN is characterized by a relapsing-and-remitting course of nephrotic syndrome (i.e. proteinuria, hypoalbuminemia, generalized edema, hyperlipidemia). Half of patients ultimately progress to chronic renal failure. Because a wide variety of plasma proteins are lost in the urine, MGN is is said to involve a "nonselective proteinuria".
Epidemiology
  • MGN represents the most common cause of nephrotic syndrome in adults and rarely occurs in children.