What is the best course of treatment for a patient with Goodpasture syndrome, on regular hemodialysis (HD) for 5 months, experiencing a flare of lung disease with heavy crepitations on the left lung and significant weight loss of 15 kg in 2 months?

Treatment of Goodpasture Syndrome with Active Pulmonary Disease Despite 5 Months of Hemodialysis

This patient requires immediate aggressive triple therapy with plasmapheresis, high-dose corticosteroids, and cyclophosphamide because they have active pulmonary hemorrhage, which is an absolute indication for treatment regardless of dialysis status or renal prognosis. 1, 2

Critical Decision Point: Pulmonary Hemorrhage Overrides Renal Considerations

All patients with pulmonary hemorrhage must be treated aggressively, regardless of kidney involvement severity or dialysis dependence. 3, 1

• The presence of heavy crepitations on the left lung with weight loss (15 kg in 2 months) strongly suggests active alveolar hemorrhage, which carries significant mortality risk if untreated 1, 4
• The standard exception to treating dialysis-dependent Goodpasture patients (those with 100% crescents and no pulmonary hemorrhage) does NOT apply here because this patient has active lung disease 3
• Retrospective studies show plasmapheresis can improve pulmonary findings and reduce mortality in this setting, with high impact and low risk 3

Immediate Treatment Protocol

Plasmapheresis

• Initiate daily plasmapheresis immediately without waiting for antibody confirmation 1, 2
• Continue daily until bleeding stops, then transition to every other day for a total of 7-10 treatments 3
• Use 60 ml/kg volume replacement with fresh frozen plasma (FFP) as replacement fluid given the active alveolar hemorrhage 1
• Continue until anti-GBM antibodies are undetectable on 2 consecutive tests 1

Corticosteroids

• Start with pulse methylprednisolone immediately (typically 500-1000 mg IV daily for 3 days) 3, 1
• Transition to oral prednisone with tapering over approximately 6 months 3, 1
• Complete glucocorticoid therapy by 6 months 1

Cyclophosphamide

• Administer oral cyclophosphamide 2-3 mg/kg daily for 2-3 months once infection is ruled out 1
• Dose-adjust for reduced GFR and consider lower dosing given 5 months of dialysis 1
• Daily oral administration is preferred over pulse therapy for 3 months 3

Essential Supportive Care

Infection Prophylaxis

• Initiate trimethoprim-sulfamethoxazole for Pneumocystis prophylaxis and continue until cyclophosphamide is complete AND prednisone dose is <20 mg daily 1
• Rule out active infection before starting cyclophosphamide, given the weight loss and pulmonary symptoms 1, 2

Monitoring During Treatment

• Check anti-GBM antibody titers to guide plasmapheresis duration 1
• Monitor for hemoptysis resolution and improvement in pulmonary infiltrates 3
• Serial chest imaging to assess response 4, 5

Addressing the Weight Loss

The 15 kg weight loss in 2 months is concerning and requires investigation:

• Rule out active infection (tuberculosis, fungal, bacterial) before intensifying immunosuppression 2, 6
• Consider malnutrition from uremia and chronic illness 7
• Evaluate for concurrent malignancy, though less likely given the clinical picture 4
• The weight loss may reflect ongoing inflammatory disease activity requiring aggressive treatment 7

Prognosis and Realistic Expectations

Renal Prognosis

• Renal recovery is extremely unlikely given 5 months of established dialysis dependence 3
• Dialysis-dependent patients at presentation have >90% chance of remaining on dialysis at 1 year 1
• The low rate of renal recovery (8%) in dialysis-dependent patients makes kidney function restoration improbable 3

Pulmonary Prognosis

• Pulmonary hemorrhage can be successfully controlled with aggressive triple therapy in most cases 3, 7
• Early intensive treatment leads to improved survival, with 90% of patients surviving the acute presentation when treated appropriately 4
• The one-year survival rate with triple therapy is 70-90% 7

Maintenance Therapy Considerations

If Isolated Anti-GBM Disease

• No maintenance immunosuppression is required after completing the initial 6-month treatment course, as relapse rate is <5% 1
• Monitor anti-GBM antibodies for at least 2 years, as rare relapses have been reported 3

If Double-Positive (Anti-GBM + ANCA)

• Maintenance therapy is mandatory if patient is both anti-GBM and ANCA-positive (occurs in 10-40% of cases) 1, 7
• Use azathioprine 1-2 mg/kg/day for at least 18 months, as these patients behave like ANCA-associated vasculitis 1
• Double-positive patients have worse renal prognosis and require long-term immunosuppression 7

Common Pitfalls to Avoid

• Do not withhold treatment because the patient is dialysis-dependent—the pulmonary hemorrhage is the treatment indication here, not renal recovery 3, 1
• Do not delay treatment waiting for antibody confirmation—begin empirical therapy immediately when pulmonary-renal syndrome is suspected 1, 2
• Do not use albumin for plasmapheresis replacement—use FFP given the active alveolar hemorrhage 1
• Do not forget to check ANCA status—if double-positive, maintenance therapy will be required 1, 7

Future Transplant Consideration

• Defer kidney transplantation until anti-GBM antibodies have been undetectable for a minimum of 6 months 1, 2
• This patient may be a transplant candidate once the acute disease is controlled and antibodies clear 3, 2