Anti-GBM Disease (Goodpasture Syndrome)

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Epidemiology & Pathophysiology

Anti-GBM disease represents 5–10% of RPGN cases and 1–2% of all GN. Annual incidence approximately 0.5–2 per million.

Target & Mechanism

• Target antigen: NC1 domain of α3 chain of type IV collagen (α3(IV)NC1)
• Located in GBM, alveolar basement membrane, and Descemet membrane
• IgG anti-GBM antibodies circulate and deposit along GBM in a linear pattern
• Classical pathway complement activation → neutrophil infiltration → crescent formation → rapid loss of renal function

Goodpasture Syndrome (~50% of patients)

Identical anti-GBM antibodies target alveolar basement membrane causing diffuse alveolar hemorrhage, hemoptysis, and pulmonary infiltrates. Can be life-threatening; often precedes renal manifestations.

Triggering Factors

• Respiratory infection (viral URI; may expose cryptic epitope)
• Smoking (induces alveolar permeability; increases pulmonary hemorrhage risk)
• Hydrocarbon exposure
• Genetic predisposition (HLA-DR2, HLA-DQ2)

Clinical Presentation

Renal-Limited Disease (50%)

• Sudden onset hematuria + proteinuria
• Progressive rise in creatinine (doubling times 24–72 hours typical)
• Dysmorphic RBC + RBC casts on UA
• No systemic symptoms (distinguishes from systemic vasculitis)

Pulmonary-Renal Syndrome

• Hemoptysis (blood-tinged sputum to life-threatening hemorrhage)
• Dyspnea, chest pain
• Diffuse alveolar infiltrates on CXR
• Anemia from ongoing hemorrhage

Laboratory Features

• Creatinine often markedly elevated (1.5–10+ mg/dL)
• Normal C3, C4 (distinguishes from immune-complex RPGN)
• Negative ANA, ANCA, cryoglobulins (seronegative RPGN pattern)
• Positive serum anti-GBM antibodies in >90% (may be transiently negative in fulminant cases)

Treatment: Triple Therapy (Urgent Initiation Required)

1. High-Dose Corticosteroids

• IV methylprednisolone 500 mg–1 g daily for 3–5 days, then oral prednisone 1 mg/kg/day
• Slow taper over 8–12 weeks

2. Cyclophosphamide

• 2 mg/kg/day oral (dose-reduced if elderly or low WBC) OR pulsed IV 1 g/m² x 3 monthly
• Duration: 8–12 weeks oral; monitor CBC weekly (target WBC 4,000–8,000)

3. Plasmapheresis

• Especially critical when Cr >5.8 mg/dL, oliguria/anuria, or fulminant pulmonary hemorrhage
• 40–60 mL/kg daily for 7–14 days or until anti-GBM antibodies undetectable
• Removes pre-formed antibodies; cyclophosphamide prevents new antibody synthesis

Prognosis

Renal Outcomes by Creatinine at Diagnosis

Biopsy: >80% crescents = poor prognosis; <50% crescents = better prognosis.

Timing: Initiation within 2 weeks of symptom onset yields much better outcomes. Initiation >4 weeks: most become ESRD.

RPGN Classification: Key Differentiating Features

Clinical Pearls

1. Linear IgG on IF is virtually pathognomonic
2. Serum anti-GBM antibodies may be transiently negative in fulminant disease; negative serology does not exclude diagnosis
3. Time to treatment is the most modifiable predictor of outcome
4. Plasmapheresis should NOT be delayed waiting for biopsy if clinical suspicion is high
5. Anti-GBM disease does NOT recur after antibodies clear
6. Dialysis initiation is not a contraindication to therapy — late renal recovery possible years later
7. Smoking cessation essential in Goodpasture syndrome

References

1. McAdoo SP, Pusey CD. Anti-GBM disease. CJASN. 2017;12(7):1162-1172. PubMed
2. Levy JB, Turner AN, Rees AJ, et al. Long-term outcome of anti-glomerular basement membrane antibody disease treated with plasma exchange and immunosuppression. Ann Intern Med. 2001;134(11):1033-1042. PubMed
3. . Chapter 14: Anti-glomerular basement membrane antibody glomerulonephritis. Kidney Int Suppl (2011). 2012;2(2):240-242. PubMed
4. Hellmark T, Johansson C, Wieslander J. Characterization of anti-GBM antibodies involved in Goodpasture's syndrome. Kidney Int. 1994;46(3):823-9. PubMed