What is the management of Anti-Glomerular Basement Membrane (Anti-GBM) disease?

Management of Anti-Glomerular Basement Membrane (Anti-GBM) Disease

Treatment for anti-GBM disease must begin immediately upon suspicion of the diagnosis, even before confirmation, with a combination of plasma exchange, high-dose glucocorticoids, and cyclophosphamide to prevent irreversible kidney damage and reduce mortality. 1

Initial Assessment and Treatment Decision

• Prompt diagnosis is crucial - send serologies for anti-GBM, ANA, and ANCA, but do not delay treatment while awaiting results 1
• Kidney biopsy provides valuable prognostic information when safe to perform - assess for acute tubular necrosis, percentage of crescents, and degree of tubular atrophy/interstitial fibrosis 1
• Factors favoring aggressive treatment include:
  • Alveolar hemorrhage (regardless of renal function) 1
  • Acute kidney injury not requiring dialysis 1
  • Acute presentation with non-oliguric renal failure 1
  • Biopsy showing <50% glomerulosclerosis, minimal tubular atrophy/interstitial fibrosis, and <100% crescents 1

First-Line Treatment Protocol

1. Plasma Exchange:

   • Begin immediately upon suspicion of anti-GBM disease 1
   • Use albumin replacement in most cases; use fresh frozen plasma if alveolar hemorrhage present or recent kidney biopsy performed 1
   • Continue until anti-GBM antibodies are undetectable on two consecutive tests 1
   • Most patients (97%) achieve undetectable antibody levels within 8 weeks 1

2. Glucocorticoids:

   • Start with high-dose methylprednisolone (solumedrol) immediately 1
   • Transition to oral prednisone, tapered over approximately 6 months 1

3. Cyclophosphamide:

   • Oral cyclophosphamide at 2-3 mg/kg daily for 2-3 months 1
   • Adjust dose for reduced GFR or older age 1
   • Consider initiating after infection has been ruled out, ideally after disease confirmation 1

4. Supportive Care:

   • Pneumocystis prophylaxis with trimethoprim-sulfamethoxazole until cyclophosphamide is complete and prednisone dose <20 mg daily 1
   • Smoking cessation is strongly recommended as hydrocarbon exposure is associated with disease activity 1

Special Considerations

• Patients on dialysis: Those presenting with dialysis-dependence have poor outcomes (35% mortality, >90% remain on dialysis at 1 year) and should only receive aggressive immunosuppression if presentation is acute, non-oliguric, or biopsy shows features of acuity 1
• Severe renal impairment: Patients with serum creatinine >5.7 mg/dL but not requiring dialysis within 72 hours can still benefit from immunosuppression 1
• ANCA co-positivity: Patients positive for both anti-GBM and ANCA antibodies require maintenance immunosuppression as for ANCA-associated vasculitis due to higher relapse rates 1
• Refractory disease: Consider rituximab or mycophenolate mofetil (MMF) for refractory cases 1, 2

Maintenance Therapy

• No maintenance therapy is necessary for isolated anti-GBM disease due to low relapse rate (<5%) 1
• Exception: Patients with dual positivity for anti-GBM and ANCA antibodies require maintenance therapy as for ANCA-associated vasculitis 1

Novel Therapies

• Imlifidase (IgG-degrading enzyme from Streptococcus pyogenes) has shown promise in phase 2 studies - a single dose combined with plasma exchange and corticosteroids resulted in rapid antibody decline within 6 hours and 67% dialysis-free survival at 6 months 1

Kidney Transplantation

• Postpone kidney transplantation until anti-GBM antibodies remain undetectable for ≥6 months 1
• Patients with Alport syndrome may develop anti-GBM antibodies to the foreign collagen chain in the transplanted kidney in approximately 2-3% of cases 1

Pitfalls and Caveats

• Do not delay treatment while awaiting confirmation of diagnosis - early treatment is critical for preserving renal function 1
• Anti-GBM antibodies can be falsely negative in approximately 10% of cases, making kidney biopsy crucial when clinically suspected 1
• Avoid undertreatment - continue plasma exchange until antibodies are undetectable, not just reduced 1
• Remember that patients with dual positivity for ANCA and anti-GBM require maintenance therapy unlike those with isolated anti-GBM disease 1