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For further information, see CMDT Part 22-13: Nephritic Spectrum Glomerular Diseases

Key Features

  • Relatively rare pattern of glomerular injury

  • Currently classified pathologically into immune-complex and C3-related disease

  • Causes of immune complex–mediated membranoproliferative glomerulonephritis (MPGN) include

    • Chronic infection (most commonly hepatitis C virus but bacterial and parasitic infections may also be causative)

    • A paraproteinemia

    • An underlying autoimmune disease, such as systemic lupus erythematosus

    • Can also be idiopathic

  • C3-related MPGN is caused by several inherited or acquired abnormalities in the alternative complement pathway

Clinical Findings

  • Low circulating C3 complement

Diagnosis

  • Light microscopy of both types shows varying degrees of mesangial hypercellularity, endocapillary proliferation and capillary wall remodeling resulting in double contours of the GBM (“tram track” appearance)

  • Immunofluorescence and electron microscopy provide distinguishing information

Immune complex–mediated disease

  • C4 is low

  • Reveals C3 and IgG and/or IgM staining on immunofluorescence

  • Electron microscopy demonstrates mesangial and subepithelial deposits

C3-related disease

  • Distinguished by lack of immunoglobulin staining on immunofluorescence

  • Can appear similar to immune complex disease with respect to light and electron microscopy

  • “Dense deposit disease”

    • Rare type of C3 glomerular injury

    • Based on thick ribbon-like deposits seen on electron microscopy

Treatment

Immune complex–mediated disease

  • Treatment should be directed at any identifiable underlying cause

  • Management of idiopathic immune complex disease is controversial

  • For those with mild disease, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers should be used

  • For severe disease,

    • A combination of oral cyclophosphamide or mycophenolate mofetil plus corticosteroids could be considered

    • Rituximab is also sometimes used

C3-related disease

  • Novel therapies to target the dysregulated alternative complement cascade are being explored

  • Eculizumab is being investigated as possible benefit

  • Plasma exchange has been used with mixed results to treat posttransplant recurrence of MPGN

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