What is the management of Goodpasture's syndrome?

Management of Goodpasture's Syndrome

Initiate immediate triple therapy with plasma exchange, high-dose corticosteroids, and cyclophosphamide as soon as Goodpasture's syndrome is suspected—do not delay treatment while awaiting confirmatory testing. 1, 2

Immediate Treatment Protocol

When to Start Treatment

• Begin treatment immediately upon clinical suspicion of anti-GBM disease, particularly in patients presenting with pulmonary-renal syndrome 1, 2
• Send serologies for anti-GBM antibodies, but do not wait for results before initiating therapy in rapidly deteriorating patients 2
• High-dose corticosteroids and plasmapheresis should be started while awaiting diagnostic confirmation 1

Triple Therapy Components

Plasma Exchange:

• Start immediately and continue daily or every other day 2, 3
• Continue until anti-GBM antibodies are undetectable on two consecutive tests, not just reduced 2
• Typical course involves 13 sessions (median range 9-17) 3
• Each session exchanges 200-250 ml/kg 2

Corticosteroids:

• Begin with high-dose intravenous methylprednisolone (pulse therapy) 2, 4
• Transition to oral prednisone and taper over approximately 6 months 2

Cyclophosphamide:

• Oral cyclophosphamide at 2-3 mg/kg daily for 2-3 months 2
• Adjust dose downward for reduced GFR or older age 2
• Evidence suggests oral cyclophosphamide may be superior to intravenous administration 3

Prognostic Stratification and Treatment Decisions

Patients with Good Prognosis (Treat Aggressively)

• Serum creatinine <500 μmol/L (5.7 mg/dL): 95% renal survival at 1 year, 74% at long-term follow-up 4
• Creatinine ≥500 μmol/L but not requiring immediate dialysis: 82% renal survival at 1 year 4
• Non-oliguric presentation with acute features on biopsy 2

Patients with Poor Prognosis (Consider Withholding Aggressive Therapy)

• Dialysis-dependent at presentation with 100% crescents on biopsy: only 8% renal survival at 1 year, 5% long-term 4

• 50% global glomerulosclerosis on biopsy 1

• Exception: Provide aggressive immunosuppression even if dialysis-dependent when pulmonary hemorrhage is present 1, 2

Special Populations

Double-Positive Patients (Anti-GBM + ANCA)

• Require maintenance immunosuppression similar to ANCA-associated vasculitis due to higher relapse rates (unlike isolated anti-GBM disease) 1, 2
• Continue monitoring and treatment beyond the typical 2-3 month cyclophosphamide course 2

Isolated Anti-GBM Disease

• No maintenance therapy necessary after initial 2-3 months due to relapse rate <5% 2
• Monitor for at least 2 years, though relapses are rare 1

Diagnostic Confirmation

Serologic Testing

• Anti-GBM antibodies are positive in approximately 90% of cases 1, 2
• Pitfall: 10% false-negative rate means kidney biopsy is crucial when clinically suspected 2

Kidney Biopsy

• Shows necrotizing and crescentic glomerulonephritis with linear IgG staining on immunofluorescence (pathognomonic) 1
• Provides critical prognostic information: percentage of crescents, degree of tubular atrophy/interstitial fibrosis 2
• Should not delay treatment initiation in rapidly progressive cases 2

Supportive Care

• Hemodialysis as needed for severe kidney injury 1, 5
• Monitor for and treat pulmonary hemorrhage aggressively 5, 4

Novel Therapies

• Imlifidase (IgG-degrading enzyme) shows promise in phase 2 studies with 67% dialysis-free survival at 6 months and rapid antibody decline within 6 hours 2

Kidney Transplantation

• Defer transplantation until anti-GBM antibodies remain undetectable for minimum 6 months 1, 2
• Patients with Alport syndrome have 2-3% risk of developing anti-GBM antibodies to the foreign collagen in the transplanted kidney 2

Critical Pitfalls to Avoid

• Delaying treatment while awaiting diagnostic confirmation in suspected cases—this is the most common error leading to irreversible kidney damage 2, 4
• Stopping plasma exchange too early—continue until antibodies are undetectable on two consecutive tests, not just improved 2
• Undertreating dialysis-dependent patients with pulmonary hemorrhage—these patients still require aggressive therapy 1, 2
• Failing to recognize double-positive patients—they need maintenance therapy unlike isolated anti-GBM disease 2

Monitoring Treatment Response

• Serial anti-GBM antibody levels to guide plasma exchange duration 5, 3
• Number of plasma exchange sessions correlates with overall survival 3
• Age <60 years is an independent predictor of better survival 3