What is the treatment for Anti-GBM (Anti-Glomerular Basement Membrane) Antibody Disease?

Treatment of Anti-GBM Antibody Disease

Treatment for anti-GBM disease must begin immediately upon suspicion of diagnosis with plasma exchange, high-dose corticosteroids, and cyclophosphamide to prevent irreversible kidney damage and reduce mortality. 1

Immediate Management

First-line Treatment

• Plasma exchange (plasmapheresis)

  • Start without delay, even before confirmation of diagnosis if strongly suspected 1
  • Continue until anti-GBM antibodies are undetectable on two consecutive tests 1
  • Most patients (97%) achieve undetectable antibodies within 8 weeks 1
  • Use albumin replacement generally, but fresh frozen plasma if pulmonary hemorrhage or recent kidney biopsy 1

• Corticosteroids

  • Begin with IV pulse methylprednisolone 1
  • Follow with oral prednisone, tapering over approximately 6 months 1

• Cyclophosphamide

  • Oral dosing at 2-3 mg/kg daily for 2-3 months 1
  • Dose should be adjusted for reduced GFR and older age 1
  • Pneumocystis prophylaxis with trimethoprim-sulfamethoxazole is required until cyclophosphamide is complete and prednisone dose is <20 mg daily 1

Prognostic Considerations

Factors affecting treatment decisions:

• Renal function at presentation:

  • Creatinine <500 μmol/L (5.7 mg/dL): excellent prognosis with 95% renal survival at 1 year 2
  • Creatinine ≥500 μmol/L but not requiring dialysis: 82% renal survival at 1 year 2
  • Dialysis-dependent at presentation: only 8% renal recovery at 1 year 2

• Kidney biopsy findings:

  • 100% crescents with dialysis dependency: extremely poor renal recovery, consider limiting aggressive treatment 1
  • Features suggesting potential recovery: acute tubular injury, <50% glomerulosclerosis, limited tubular atrophy/interstitial fibrosis, <100% crescents 1

• Pulmonary involvement:

  • All patients with pulmonary hemorrhage should receive full treatment regardless of renal status 1

Special Considerations

ANCA Co-positivity

• Approximately 30% of anti-GBM patients are also ANCA positive 3
• These "double-positive" patients require maintenance immunosuppression as for ANCA-associated vasculitis 1
• Relapse rates are higher in double-positive patients 1

Refractory Disease

• For patients not responding to standard therapy, consider:
  • Rituximab 1
  • Mycophenolate mofetil 1, 4
  • Clinical trial enrollment where available 1
  • Imlifidase (IgG-degrading enzyme) shows promise in early studies with 67% dialysis-free survival at 6 months 1

Maintenance Therapy

• No maintenance therapy is needed for isolated anti-GBM disease 1
• Relapse rate is <5% in properly treated patients 1
• Smoking cessation is strongly recommended as hydrocarbon exposure is associated with disease activity 1

Kidney Transplantation

• Defer transplantation until anti-GBM antibodies have been undetectable for at least 6 months 1
• Risk of recurrence is very low when antibodies are absent for this period 1
• Special consideration for Alport syndrome patients: 2-3% develop anti-GBM antibodies to foreign collagen chains in transplanted kidneys 1

Pitfalls and Caveats

1. Delayed treatment: Even hours of delay can lead to irreversible kidney damage; start treatment on strong suspicion before confirmation 1

2. Inadequate duration of plasma exchange: Continue until antibodies are undetectable, not for a fixed period 1

3. Overtreatment of end-stage cases: Patients with dialysis dependency and 100% crescents have <5% chance of renal recovery; consider limiting aggressive immunosuppression to reduce complications 1

4. Missing pulmonary involvement: Always evaluate for pulmonary hemorrhage, which increases mortality risk 3

5. Overlooking double-positivity: Test for both anti-GBM and ANCA antibodies, as management differs for double-positive patients 1, 3