Membranoproliferative Glomerulonephritis

Membranoproliferative glomerulonephritis (MPGN) is a histological pattern of glomerular injury with mesangial proliferation and capillary wall thickening ("tram-track" double contours). It is now classified by immunofluorescence.

• Immune complex mediated MPGN: chronic infection (hepatitis C with cryoglobulinaemia, hepatitis B, endocarditis, infected shunt, abscess, malaria, schistosomiasis), autoimmune disease (SLE, Sjögren, rheumatoid arthritis), monoclonal gammopathy.
• Complement mediated: C3 glomerulopathy (dense deposit disease and C3 glomerulonephritis) from alternative pathway dysregulation (C3 nephritic factor, factor H or complement gene mutations).
• Idiopathic immune complex form, mainly in children and young adults.
• Prognosis: ESKD in 40 to 50% at 10 years for primary disease; depends on cause.
• Complications: nephrotic syndrome, hypertension, progressive CKD, recurrence after transplantation (up to 80% in dense deposit disease).

• Nephrotic syndrome (50%), nephritic syndrome, asymptomatic proteinuria and haematuria.
• Hypertension, oedema, reduced GFR.
• Cryoglobulinaemia: purpura, arthralgia, neuropathy.
• Partial lipodystrophy and drusen (retinal) in dense deposit disease.
• Features of the underlying infection or autoimmune disease.

• Proteinuria, haematuria, reduced eGFR.
• Low C3 (C4 low in classical pathway disease, C4 normal in alternative pathway disorders); C3 nephritic factor, factor H and complement genetic analysis, soluble C5b-9.
• Biopsy with immunofluorescence: IgG and C3 (immune complex), or C3 dominant with minimal immunoglobulin (C3 glomerulopathy); electron microscopy for dense deposits.
• Search for cause: hepatitis B/C serology and viral load, HIV, blood cultures, echocardiography, cryoglobulins, rheumatoid factor, ANA, anti-dsDNA, serum and urine protein electrophoresis with free light chains, bone marrow biopsy if monoclonal protein.

• Treat the cause:
  • Hepatitis C: direct-acting antivirals (sofosbuvir/velpatasvir 400/100 mg daily for 12 weeks), with rituximab 375 mg/m2 weekly for 4 in severe cryoglobulinaemic disease.
  • Hepatitis B: tenofovir alafenamide 25 mg or entecavir 0.5 mg daily.
  • Endocarditis or infected shunt: appropriate antibiotics and removal of focus.
  • Lupus and Sjögren: appropriate immunosuppression.
  • Monoclonal gammopathy: clone directed therapy (bortezomib, daratumumab, rituximab).
• Supportive care: ACE inhibitor or ARB, blood pressure control, SGLT2 inhibitor, statin, diuretics, sodium restriction.
• Idiopathic immune complex MPGN with nephrotic syndrome or declining GFR: prednisolone 1 mg/kg (maximum 60 mg) tapered with mycophenolate mofetil 1 to 1.5 g twice daily, or rituximab; cyclophosphamide for crescentic disease.
• C3 glomerulopathy: mycophenolate mofetil with steroids, eculizumab 900 mg weekly for 4 weeks then 1200 mg every 2 weeks in rapidly progressive disease, iptacopan 200 mg twice daily, pegcetacoplan (C3 inhibitor); plasma exchange/infusion for factor H deficiency.
• Antiplatelet therapy (aspirin, dipyridamole) has historical use.
• Monitor eGFR, protein and complement every 3 months.
• Transplantation with recurrence surveillance.