Goodpasture's Syndrome: Characteristics and Treatment
Goodpasture's syndrome is an autoimmune disease that involves both pulmonary and renal systems, often requiring dialysis as treatment, but it is not a form of polycystic kidney disease (PKD) nor is it typically asymptomatic.
Key Characteristics of Goodpasture's Syndrome
Goodpasture's syndrome is characterized by anti-glomerular basement membrane (anti-GBM) antibodies causing damage to both pulmonary and renal systems, classically presenting as a pulmonary-renal syndrome 1, 2.
It is definitively an autoimmune disease where antibodies target the noncollagenous (NC1) domain of the α3 chain of type IV collagen present in glomerular and alveolar basement membranes 1, 3.
The disease manifests as rapidly progressive glomerulonephritis and/or pulmonary hemorrhage, making it symptomatic and often severe rather than asymptomatic 4, 5.
Goodpasture's syndrome is NOT a form of polycystic kidney disease (PKD), which is a genetic disorder; rather, it is an acquired autoimmune condition 1, 2.
Clinical Presentation and Diagnosis
Patients typically present with symptoms including cough, hemoptysis, dyspnea, fatigue, and signs of kidney dysfunction rather than being asymptomatic 2, 5.
Diagnosis should be made without delay in all patients with suspected rapidly progressive glomerulonephritis (RPGN) 1.
Laboratory testing includes anti-GBM antibodies, which are positive in most cases, though approximately 10% may be falsely negative 1.
Kidney biopsy typically shows necrotizing and crescentic glomerulonephritis with linear immunofluorescent staining for IgG on the GBM 1, 5.
Treatment Approach
Immediate aggressive treatment is recommended with cyclophosphamide, corticosteroids, and plasmapheresis for all patients with anti-GBM GN except those who are dialysis-dependent at presentation, have 100% crescents or >50% global glomerulosclerosis on biopsy, and do not have pulmonary hemorrhage 1.
Treatment should begin without delay once the diagnosis is confirmed; if highly suspected, it's appropriate to begin high-dose corticosteroids and plasmapheresis while awaiting confirmation 1.
Plasmapheresis is crucial for removing pathogenic antibodies and is typically continued for 14 days or until the anti-GBM antibody is undetectable 1, 4.
Patients with pulmonary hemorrhage should be treated regardless of the presence or severity of kidney involvement 1.
Prognosis and Long-term Management
Dialysis may be required as treatment, particularly in patients with severe kidney injury at presentation 1.
Predictors of poor renal outcome include serum creatinine >5.7 mg/dL at presentation, dialysis dependence at presentation, and extensive crescents on kidney biopsy 4.
The disease is typically monophasic and self-limited, with antibodies often disappearing spontaneously after 6-18 months 1.
Kidney transplantation should be deferred until anti-GBM antibodies have been undetectable for a minimum of 6 months 1.
With early and intensive treatment, approximately 90% of patients survive the acute presentation, though many may require long-term dialysis 2, 6.
Special Considerations
Some patients may have both anti-GBM antibodies and ANCA (double-positive), requiring careful treatment consideration 1.
Environmental triggers may include tobacco smoking, hydrocarbon solvent exposure, and cocaine abuse 2.
Relapses are rare but have been reported, necessitating ongoing monitoring for at least the first 2 years 1.