What is the management approach for a patient with Goodpasture syndrome who is on regular hemodialysis (HD) due to impaired renal function?

Management of Goodpasture Syndrome in Patients on Regular Hemodialysis

Critical Decision Point: To Treat or Not to Treat

For patients with Goodpasture syndrome who are already dialysis-dependent at presentation, immunosuppressive therapy should be withheld if they have 100% crescents (or >50% global glomerulosclerosis) on kidney biopsy AND no pulmonary hemorrhage. 1, 2

When NOT to Treat (All Three Criteria Must Be Present):

• Dialysis-dependent at presentation 1, 2
• 100% crescents on adequate biopsy sample (or >50% global glomerulosclerosis) 1, 2
• No pulmonary hemorrhage 1, 2

The rationale is that such patients have <8% chance of renal recovery, making the risks of aggressive immunosuppression (including a 35% mortality rate from severe infection) difficult to justify. 1, 2

When TO Treat Despite Dialysis Dependence:

Treat aggressively with triple therapy if ANY of the following apply:

• Pulmonary hemorrhage is present (regardless of renal status or biopsy findings) 1, 2
• <100% crescents on biopsy (indicating some viable glomeruli) 1, 2
• **Dialysis initiated within <72 hours of presentation** (even with creatinine >500 μmol/L, as this indicates rapid progression rather than chronic damage) 2
• Functionally young patients with very rapid loss of kidney function may warrant a limited 4-8 week trial of therapy 1

Treatment Protocol for Dialysis Patients Who Meet Treatment Criteria

Immediate Triple Therapy (Start Without Delay):

1. High-Dose Corticosteroids: 1, 2

• Pulse methylprednisolone initially 1, 2
• Transition to oral prednisone with tapering over 6 months 1, 2

2. Plasmapheresis: 1, 2

• Continue daily until anti-GBM antibodies are undetectable on 2 consecutive tests 1, 2
• Typically 14 days or until antibody negativity 1
• Use fresh frozen plasma replacement if alveolar hemorrhage present or recent kidney biopsy performed; otherwise albumin is sufficient 2

3. Cyclophosphamide: 1, 2

• Oral cyclophosphamide 2-3 mg/kg daily for 2-3 months 1, 2
• Dose-adjust for reduced GFR (critical in dialysis patients) 1, 2
• Can be added after ruling out infection, ideally after disease confirmation 2

Supportive Care:

Pneumocystis Prophylaxis: 1, 2

• Trimethoprim-sulfamethoxazole until cyclophosphamide is complete AND prednisone <20 mg daily 1, 2

Smoking Cessation: 1

• Strongly recommended as hydrocarbon exposure is associated with disease activity 1

Maintenance Therapy Considerations

For isolated anti-GBM disease: No maintenance immunosuppression is required after initial treatment, as relapse rate is <5%. 1, 2

For double-positive patients (anti-GBM + ANCA): Maintenance therapy as for ANCA-associated vasculitis IS required, as these patients have relapse rates equivalent to AAV (up to 30% of anti-GBM patients are double-positive). 1, 2

Kidney Transplantation Timing

Defer kidney transplantation until anti-GBM antibodies have been undetectable for a minimum of 6 months. 1, 2

Recurrence of anti-GBM disease after transplantation is very low in patients without detectable antibodies. 1

Prognosis for Dialysis-Dependent Patients

• Mortality rate: 35% at 1 year for dialysis-dependent patients at presentation 2
• Renal recovery: >90% remain on dialysis at 1 year 2
• Survival benefit: Being aged <60 years and higher number of plasma exchange sessions correlate with overall survival 3
• Infection risk: 7/16 deaths in one series were from severe infection, highlighting the risk of aggressive immunosuppression 3

Critical Pitfalls to Avoid

• Do not delay treatment waiting for biopsy confirmation if clinical suspicion is high—begin empirical therapy immediately 1, 2
• Always treat pulmonary hemorrhage regardless of renal involvement severity or biopsy findings 1, 2
• Do not forget maintenance therapy in double-positive (anti-GBM + ANCA) patients—they behave like AAV, not isolated anti-GBM disease 1, 2
• Do not withhold treatment from patients with severe renal impairment (creatinine >500 μmol/L) if they are not yet dialysis-dependent 2

Emerging Therapies

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 in a phase 2 study. 2