Goodpasture Syndrome

Goodpasture Syndrome

Anti-glomerular basement membrane disease (anti-GBM disease), also known as Goodpasture disease, is a rare, autoimmune, small-vessel vasculitis affecting blood vessels of the lungs and kidneys that results in a pulmonary-renal syndrome.

A pulmonary-renal syndrome is defined as the coexistence of pulmonary alveolar hemorrhage (i.e., triad of hemoptysis, diffuse alveolar infiltrates, and anemia) and acute kidney injury (AKI) from rapidly progressive glomerulonephritis (RPGN).

Importantly, a pulmonary-renal syndrome may affect only the kidneys (AKI and RPGN) or the kidneys and lungs simultaneously. In rare instances, only the lungs are involved.

Synonyms

• Anti-glomerular basement membrane disease
• Goodpasture Disease

Epidemiology & Demographics

• •Anti-GBM disease has a bimodal age distribution, predominantly affecting young, white, male smokers. The second most-commonly affected group is older adults (>50 yr old; women more than men)
• •Goodpasture disease accounts for 5% to 15% of all cases of RPGN
• •HLA-DR2 locus is present in 80% of patients
• •Approximately 20% to 40% of patients with anti-GBM antibody have positive anti-neutrophil cytoplasmic autoantibodies (ANCAs)
• •Anti-GBM disease can also occur with other glomerular diseases, such as ANCA- vasculitis, lupus, and membranous nephropathy
• •Anti-GBM disease can occur in up to 5% of newly transplanted kidneys in Alport disease patients, resulting from newly formed antibodies
• •Secondary anti-GBM disease may occur in patients treated with immunomodulatory agents or in other autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, celiac disease, ulcerative colitis, and infective endocarditis

Physical Findings & Clinical Presentation

• •Dyspnea, cough, hemoptysis
• •Skin pallor, fever, arthralgias (may be mild or absent at the time of initial presentation)
• •Hematuria may be noted
• •Frothy urine resulting from proteinuria, although nephrotic syndrome is uncommon

What causes Goodpasture Syndrome?

Anti-GBM disease is caused by autoantibodies directed against the alpha-3 chain of type IV collagen, a primary component of the glomerular basement membrane GBM of lungs and kidneys. Antibody deposition leads to immunologic, inflammatory damage with pulmonary hemorrhage and glomerulonephritis. With appropriate treatment, antibody titers decline. Relapse with antibody production is rare.

Differential Diagnosis

• •Granulomatosis with polyangiitis, formerly Wegener granulomatosis
• •Systemic lupus erythematosus
• •Eosinophilic granulomatosis with polyangiitis (eGPA), formerly Churg-Strauss syndrome
• •Essential mixed cryoglobulinemia
• •Idiopathic rapidly progressive glomerulonephritis
• •Drug-induced renal pulmonary disease (e.g., penicillamine)

How is Goodpasture Syndrome diagnosed?

Laboratory and clinical evaluation, diagnostic imaging, and kidney biopsy

Laboratory & Clinical Tests

• •Serum anti-GBM antibodies (commercial enzyme-linked immunosorbent assay [ELISA] have 95% sensitivity and 95% to 99% specificity)
• •Normal serum complement (C3 and C4) levels
• •Absence of circulating immune complexes, ANCAs (except with overlap syndrome), and cryoglobulins
• •Urinalysis with microscopic hematuria, proteinuria, and red blood cell casts
• •Urine protein-to-creatinine ratio to quantitate proteinuria
• •Elevated blood urea nitrogen and creatinine
• •Immunofluorescence studies of kidney biopsy specimens with anti-GBM antibody demonstrate a linear staining pattern, often with C3 deposition
• •Complete blood count and serum iron studies may reveal iron-deficiency anemia from urinary and pulmonary blood losses
• •Bronchoalveolar lavage may show alveolar hemorrhage and exclude an infection

Imaging Studies

Chest radiograph with airspace disease composed of alveolar infiltrates or evidence of pulmonary hemorrhage

How is Goodpasture Syndrome treated?

Acute General Treatment

• •Plasmapheresis with albumin replacement for 1 to 2 wk (use fresh frozen plasma if bleeding risk present). Immunosuppression typically composed of prednisone (1 mg/kg/day) and oral cyclophosphamide (2 mg/kg/day). Intravenous cyclophosphamide has been used at some institutions. Rituximab has not been studied in clinical trials and has been used in patients who were not candidates for cyclophosphamide treatment.
• •Hemodialysis, if kidney failure occurs.
• •Factors influencing treatment decisions in Goodpasture disease are described in the below table.

Factors Influencing Decision to Treat Aggressively in Goodpasture Disease

From Floege J et al: Comprehensive clinical nephrology, ed 5, Philadelphia, 2015, Saunders.

	Factors Favoring Aggressive Treatment	Factors Against Aggressive Treatment (predictors of poor renal outcomes)
Pulmonary hemorrhage	Present	Absent
Oliguria	Absent	Present
Creatinine	<5.5 mg/dl (∼500 mmol/L)	>5.5-6.5 mg/dl (∼500-600 mmol/L) and ANCA negative Severe damage on kidney biopsy No desire for early kidney transplantation
Other factors	Creatinine >5.5-6.5 mg/dl (∼500-600 mmol/L) but Rapid and recent progression ANCA positive Less severe glomerular damage Crescents, nonfibrotic Early renal transplantation is optimal
Associated disease	Absent	Unusually high risk from immunosuppression

ANCA, Anti-neutrophil cytoplasmic autoantibody.

Disposition

Life-threatening pulmonary hemorrhage and irreversible glomerular damage are major causes of death.

Referral

• •Referral for kidney biopsy to guide management
• •Consider kidney transplantation in patients with end-stage renal disease

Seek Additional Information

• Falk R.J., et al.: Case 24–2018: a 71-year-old man with acute renal failure and hematuria. N Engl J Med 2018; 379 (6): pp. 568-578.
• Greco A., et al.: Goodpasture’s syndrome: a clinical update. Autoimmun Rev 2015; 14 (3): pp. 246-253.
• McAdoo S.P., Pusey C.D.: Anti-glomerular basement membrane disease. Clin J Am Soc Nephrol 2017; 12 (7): pp. 1162-1172.
• Pedchencko V., et al.: Molecular architecture of the Goodpasture autoantigen in anti-GBM nephritis. N Engl J Med 2010; 363: pp. 343-354.