How should type 1 rapidly progressive glomerulonephritis (anti‑GBM disease) be managed from initial hospitalization through outpatient follow‑up?

Management of Type 1 RPGN (Anti-GBM Disease) from Hospitalization to Outpatient Follow-up

Immediate Treatment Initiation (Do Not Delay)

Start triple therapy immediately upon clinical suspicion with plasmapheresis, pulse methylprednisolone, and cyclophosphamide—do not wait for antibody confirmation. 1, 2, 3

Initial Assessment and Treatment Decision

• Send serologies for anti-GBM, ANCA, and ANA immediately, but begin empirical treatment without waiting for results 2
• Perform kidney biopsy when safe to assess percentage of crescents, degree of tubular atrophy/interstitial fibrosis, and presence of acute tubular necrosis for prognostic information 2
• Critical exception: Withhold immunosuppression ONLY if the patient is dialysis-dependent at presentation AND has 100% crescents (or >50% global glomerulosclerosis) on adequate biopsy AND has no pulmonary hemorrhage 1, 3

Prognostic Indicators for Treatment Decisions

Favorable indicators for treatment response:

• Not requiring dialysis within 72 hours of presentation, even with creatinine >500 μmol/L (>5.7 mg/dL) 3, 4
• Creatinine <500 μmol/L at presentation (100% patient survival and 95% renal survival at 1 year) 4
• Presence of alveolar hemorrhage (always treat regardless of renal status) 3

Poor prognostic indicators:

• Dialysis-dependent at presentation (35% mortality rate, >90% remain on dialysis at 1 year) 3, 4
• 100% crescents on biopsy in dialysis-dependent patients (all remain dialysis-dependent) 4
• Oliguric presentation (none recovered renal function in historical cohorts) 5

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First-Line Treatment Protocol (Induction Phase)

1. Plasmapheresis

• Start immediately upon suspicion, perform daily 4-liter plasma exchanges 2, 5
• Continue until anti-GBM antibodies are undetectable on two consecutive tests (typically 2 weeks) 2, 3, 5
• Use fresh frozen plasma for replacement if alveolar hemorrhage is present or recent kidney biopsy was performed; otherwise albumin replacement is sufficient 3

2. Corticosteroids

• Begin with pulse methylprednisolone (dose not specified in guidelines, but typically 500-1000 mg IV daily for 3 days) 2, 3
• Transition to oral prednisone 60 mg daily, reducing to 20 mg daily by 4 weeks 5
• Taper over approximately 6 months, completing glucocorticoid therapy by 6 months 2, 3

3. Cyclophosphamide

• Oral cyclophosphamide 2-3 mg/kg daily for 2-3 months 2, 3
• Adjust dose for reduced GFR or older age 2, 3
• Add empirically once infection is ruled out, ideally after disease confirmation 3

4. Prophylaxis

• Trimethoprim-sulfamethoxazole for Pneumocystis prophylaxis until cyclophosphamide is complete AND prednisone dose is <20 mg daily 3

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Special Populations and Considerations

Dual-Positive Patients (Anti-GBM + ANCA)

• These patients behave like ANCA-associated vasculitis, not isolated anti-GBM disease 2, 3
• Require maintenance immunosuppression as for ANCA-associated vasculitis due to higher relapse rates (equivalent to AAV patients) 2, 3
• Do not stop immunosuppression after induction phase 3

Dialysis-Dependent Patients

• Have poor outcomes overall (65% patient survival and 8% renal survival at 1 year) 4
• Only receive aggressive immunosuppression if presentation is acute, non-oliguric, or biopsy shows features of acuity (not 100% crescents) 2
• Patients with 100% crescents and no pulmonary hemorrhage should not receive immunosuppression 1

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Maintenance Therapy and Long-Term Management

Isolated Anti-GBM Disease

• No maintenance immunosuppressive therapy is necessary due to low relapse rate (<5%) 1, 2, 3
• Relapses are rare in classic anti-GBM disease, unlike ANCA-associated vasculitis 6

Monitoring During Follow-up

• Monitor anti-GBM antibody levels; antibody typically becomes undetectable within 8 weeks of treatment 5
• Anti-GBM antibodies can be falsely negative in approximately 10% of cases 2
• Continue plasma exchange until antibodies are undetectable, not just reduced 2

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Kidney Transplantation Timing

• Defer kidney transplantation until anti-GBM antibodies have been undetectable for a minimum of 6 months 1, 3
• Patients with Alport syndrome may develop anti-GBM antibodies to the foreign collagen chain in the transplanted kidney in approximately 2-3% of cases 2

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Emerging Therapies

• Imlifidase (IgG-degrading enzyme from Streptococcus pyogenes) has shown promise in phase 2 studies 2, 3
• Rapid antibody decline within 6 hours and 67% dialysis-free survival at 6 months 2, 3
• Future research should define the role of rituximab and determine the place of imlifidase 6

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Critical Pitfalls to Avoid

• Do not delay treatment waiting for biopsy confirmation—begin empirical therapy immediately when suspected 2, 3
• Do not withhold treatment from patients with severe renal impairment (creatinine >500 μmol/L) if they are not yet dialysis-dependent 3, 4
• Always treat pulmonary hemorrhage, regardless of renal involvement severity 3
• Do not forget maintenance therapy in double-positive (anti-GBM + ANCA) patients—they behave like AAV, not isolated anti-GBM disease 2, 3
• Do not stop plasma exchange prematurely—continue until antibodies are undetectable on two consecutive tests, not just reduced 2
• Early treatment is critical for preserving renal function; time to diagnosis is a major determinant of outcomes 1, 7