Glomerulonephritis, Membranoproliferative

Key Features

• Relatively rare pattern of glomerular injury

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

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

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

  • A paraproteinemia

  • An underlying autoimmune disease, such as systemic lupus erythematosus

  • Can also be idiopathic

• C3 glomerulopathies are 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; others may respond to mycophenolate mofetil

• Plasma exchange, with or without eculizumab, has been used with mixed results to treat posttransplant recurrence of MPGN