• Characterized by diffuse mesangial cell proliferation, endocapillary proliferation, and thickening of glomerular basement membrane9
  • MPGN was previously classified into 3 categories based on histological findings (Types I, II, and III). Presently, a new classification system has been developed based on pathophysiology:
    • Immune complex-mediated MPGN – defined by deposition of immune complexes within the glomeruli, leading to an influx of inflammatory cells in the mesangium and capillary loops (formerly classified mostly type I)6
    • Complement-mediated MPGN – defined by deposition of complement products in the mesangium and capillary walls
      • Dense deposit disease (DDD) - MPGN with intramembranous dense deposits (formerly classified type II)
      • Component 3 glomerulonephritis (C3GN) without dense deposits (formerly classified mostly type III)9
    • With varying forms of MPGN, patients may present with microhematuria and non-nephrotic proteinuria, nephrotic syndrome with mild renal insufficiency, clinically progressive GN, or as nephritic syndrome with proteinuria and red blood cell casts
    • Typically idiopathic for children, but often secondary to cryoglobulinemia and Hepatitis C infection in adults
    • Causes <5% of all primary GN in North America and Europe
    • Accounts for 5-10% of causes of nephrotic syndrome in adults and children
    • No gender dominance
    • Most commonly found in Caucasians in the United States
    • Prognosis is poor for children and adults
      • Children: 40-50% progress to ESRD after 10 years
      • Adults: 50% die or need renal replacement therapy6

    ESRD: end-stage renal disease; GN: glomerulonephritis.

Recommendations are based on the KDIGO Clinical
Practice Guideline for Glomerulonephritis

  • Treatment aimed towards reducing proteinuria to slow progression of ESRD only for patients with idiopathic MPGN
    • Secondary MPGN should be directly treated for the underlying cause
    • Prognosis goals: prevention of ESRD
  • Options are based on progression of renal failure
  • Initial therapy upon diagnosis should consist of daily or alternating-day doses of corticosteroids combined with cyclophosphamide or MMF
    • Limit treatment to less than 6 months10

Alternative options not listed in 2012 KDIGO Guidelines

  • Idiopathic MPGN
    • CNIs may be used if patients cannot tolerate corticosteroids
    • Rituximab is suggested if treatment with cyclophosphamide is unsuccessful
  • C3 glomerulonephritis
    • No trials have been evaluated for therapy options12
  • Dense deposit disease
    • Immunosuppressive therapies are unsuccessful
    • Pulse steroids (methylprednisone) may be used for patients with rapidly progressive glomerulonephritis13
  • The product is an FDA approved treatment option11

CNI: calcineurin inhibitor; ESRD: end-stage renal disease; MMF: mycophenolate mofetil

Treatment Options
Immunosuppressive Therapy
  • Prednisone
  • Methylprednisone
  • Cytotoxic Agents10
  • Cyclophosphamide (Cytoxan®)
  • Calcineurin Inhibitors12
  • Cyclosporine (Gengraf®)
  • Tacrolimus (Prograf®)
  • Immunosuppressive Agents10
  • Mycophenolate mofetil (CellCept®)
  • Monoclonal Antibodies12
  • Rituximab (Rituxan®)
  • Acthar® Gel11*

    *FDA approved, but not enough contemporaneous data for KDIGO to make a use recommendation