What is the treatment for Goodpasture's disease?

Treatment of Goodpasture's Disease (Anti-GBM Disease)

Initiate immediate triple therapy with cyclophosphamide, high-dose corticosteroids, and plasmapheresis without delay when Goodpasture's disease is suspected—even before diagnostic confirmation—unless the patient is dialysis-dependent with 100% crescents on biopsy and no pulmonary hemorrhage. 1

Immediate Treatment Initiation

Start empirical therapy immediately when anti-GBM disease is suspected:

• Begin pulse methylprednisolone (typically 500-1000 mg IV daily for 3 days) and plasmapheresis as soon as the diagnosis is considered, before waiting for antibody confirmation 1
• Cyclophosphamide can be added empirically once infection is ruled out, but ideally after disease confirmation 1
• Use fresh frozen plasma for plasmapheresis replacement if alveolar hemorrhage is present or recent kidney biopsy was performed; otherwise albumin replacement is sufficient 1
• This aggressive approach is justified because untreated disease causes high morbidity and mortality, and renal recovery is strongly tied to early diagnosis 1

Complete Treatment Regimen

Plasmapheresis Protocol

• Continue daily plasmapheresis until anti-GBM antibodies are undetectable on 2 consecutive tests 1
• Typically requires 14 days of treatment, though 97% of patients achieve undetectable antibodies within 8 weeks 1
• Median number of sessions is approximately 13 2

Cyclophosphamide Dosing

• Oral cyclophosphamide 2-3 mg/kg daily for 2-3 months, dose-adjusted for reduced GFR or older age 1
• Oral cyclophosphamide may be superior to intravenous administration 2

Corticosteroid Regimen

• Start with pulse methylprednisolone, then transition to oral prednisone with tapering over approximately 6 months 1
• Complete glucocorticoid therapy by 6 months 1

Prophylaxis

• Trimethoprim-sulfamethoxazole for Pneumocystis prophylaxis until cyclophosphamide is complete AND prednisone dose is <20 mg daily 1

Critical Exception: When NOT to Treat

Withhold immunosuppression in patients who are:

• Dialysis-dependent at presentation AND
• Have 100% crescents (or >50% global glomerulosclerosis) on adequate biopsy AND
• Have no pulmonary hemorrhage 1, 3

However, consider a limited 4-8 week treatment trial in functionally young patients with very rapid kidney function loss, even if dialysis-dependent, if the presentation is acute, nonoliguric, and/or biopsy shows features of acuity (acute tubular injury, <50% glomerulosclerosis, <100% crescents) 1

Prognostic Indicators for Treatment Response

Favorable indicators (treat aggressively):

• Serum creatinine <500 μmol/L (5.7 mg/dL) at presentation—these patients have 95% renal survival at 1 year 4
• Not requiring dialysis within 72 hours of presentation, even with creatinine >500 μmol/L 1
• Alveolar hemorrhage present (always treat regardless of renal status) 1, 3
• AKI not requiring dialysis 1

Poor prognostic indicators:

• Dialysis-dependent at presentation: 35% mortality rate and >90% remain on dialysis at 1 year 1
• 100% crescents on biopsy with dialysis requirement: only 8% renal recovery 1

Maintenance and Long-Term Management

No maintenance immunosuppressive therapy is necessary for isolated anti-GBM disease because the relapse rate is <5% 1

Critical Exception: Double-Positive Patients

Patients who are both anti-GBM and ANCA-positive require maintenance therapy as for ANCA-associated vasculitis because their relapse rates are equivalent to AAV patients, not isolated anti-GBM disease 1

Monitoring

• Monitor patients for at least the first 2 years, as relapses are rare but have been reported 1, 3
• Strongly recommend smoking cessation, as hydrocarbon exposure is associated with disease activity 1

Kidney Transplantation Timing

Defer kidney transplantation until anti-GBM antibodies have been undetectable for a minimum of 6 months 1, 3

Emerging Therapies

A phase 2 study of imlifidase (an IgG-degrading enzyme) combined with plasma exchange and corticosteroids showed rapid antibody decline within 6 hours and 67% dialysis-free survival at 6 months 1

Common Pitfalls to Avoid

• Do not delay treatment waiting for biopsy confirmation—begin empirical therapy immediately when suspected 1
• Do not withhold treatment from patients with severe renal impairment (creatinine >500 μmol/L) if they are not yet dialysis-dependent 1, 4
• Always treat pulmonary hemorrhage regardless of renal involvement severity 1
• Do not forget maintenance therapy in double-positive (anti-GBM + ANCA) patients—they behave like AAV, not isolated anti-GBM disease 1
• Approximately 10% of patients may have false-negative anti-GBM antibodies, making kidney biopsy essential for diagnosis 3, 5