Membranoproliferative Glomerulonephritis

Overview
  • Membranoproliferative Glomerulonephritis (MPGN) is a disease defined principally by a unique histopathology that can manifest as a spectrum between nephrotic syndrome and nephritic syndrome. Two morphological subtypes, Type I and Type II MPGN, have been distinguished.
Morphology
  • Light Microscopy
    • MPGN is characterized by enlarged and lobulated glomeruli that display mesangial cell proliferation. Additionally, the glomerular basement membrane is thickened. Characteristically, mesangial cell processes infiltrate within the glomerular basement membrane, splitting it on either side, thus giving it a 'Tram-track' appearance.
  • Immunofluorescence
    • Type I MPGN: Presence of IgG and complement within the glomerular barrier
    • Type II MPGN: Presence of complement but absence of IgG within the glomerular barrier
  • Electron Microscopy
    • Type I MPGN: Clumps of likely immune complexes are incorporated within the glomerular basement membrane and lie just under the glomerular capillary endothelium, and are thus termed 'Subendothelial' deposits.
    • Type II MPGN: Presence of a highly electron dense ribbon of unknown composition within the glomerular basement membrane which is sometimes termed a "Dense Deposit".
Etiology
  • Type I MPGN
  • Type II MPGN
    • Type II MPGN may be due to the presence of a circulating auto-antibodies which binds and stabilizes C3 convertase that consequently locally activate the complement cascade. This is thought to locally generate pools of active complement proteins which then deposit in the glomerular basement membrane explaining the presence of complement but no IgG on immunofluorescence.
Clinical Consequences
  • Individuals with MPGN can present within a spectrum between nephrotic and nephritic syndrome. Recall that nephrotic syndrome is characterized by: proteinuria, hypoalbuminemia, generalized edema, hyperlipidemia. In contrast, nephritic syndrome is characterized by: hematuria, pyuria, hypertension, oliguria, and azotemia. Hypocomplementemia is also observed, especially in those with Type II MPGN, due to chronic activation and deposition of complement proteins. Prognosis is generally poor and many patients progress to chronic renal failure.
Epidemiology
  • MPGN is generally observed in adults