Time-limited (2 to 48 months) autoimmune disease with
circulating antiglomerular basement membrane (anti-GBM) antibodies affecting
the lungs and the kidneys of unknown cause (viral and streptococcal
infections and exposure to hydrocarbon fumes have been suggested as causes).
Often lethal during the acute phase; most patients who survive progress to
end-stage renal disease.
Antiglomerular Basement Membrane Disease.
Autoimmune disease, the major antigen target is
the carboxyl terminus of the noncollagenous (NC-1) domain of the α3-chain in type IV (basement membrane) collagen. The antibodies are
directed against a 28-kDa monomeric subunit present within the
noncollagenous domain. The disease may also occur in the transplanted
kidneys of patients with Alport syndrome. There is an inherited
predisposition to this syndrome (HLA-DRw2 is associated with anti-GBM
1:100,000 people, most often males approximately 20
years old. White people are more affected than black people, as are certain
ethnic groups (e.g., Maoris of New Zealand). A bimodal distribution has been
reported (young men presenting with a pulmonary-renal syndrome and elderly
women presenting mainly with glomerulitis).
Genetic predisposition depends on genes
localized on chromosomes 2 and 6.
The primary cause of the syndrome is the presence
of antibodies directed against specific collagen chains, which are present in the
glomerular and the pulmonary alveolar capillary basement membrane. Following an initiating event, for
example infection or toxin exposure, an autoimmune response is set in
motion, resulting in crescentic glomerulonephritis and progressive
deterioration in renal function and leakage of blood from alveolar
capillaries into the air spaces.
The presence of bound anti-GBM antibodies in renal
glomeruli is diagnostic. The antibodies are usually IgG, but may be IgA or
IgM. Circulating anti-GBM antibodies are present in 90% of patients.
Radioimmunoassays are more specific and sensitive than anti-GBM analysis.
These findings, in addition to the presence of pulmonary hemorrhage, are
pathognomonic of Goodpasture syndrome.
Hemoptysis ranging from blood-streaked sputum to
massive hemorrhage is commonly the presenting feature. Patients may complain
of dyspnea and cough. Pulmonary hemorrhage may be associated with severe
hypoxemia and death. Intubation, assisted ventilation, and hemodialysis are
often required in the acute phase. Renal function can range from normal to
severe insufficiency, and the deterioration in renal function can occur
rapidly. Some proteinuria is common, but nephrotic syndrome is rare.
Hypertension is an unusual finding. Renal ultrasonography is usually normal.
Pulmonary hemorrhage is often responsive to pulse methylprednisolone
therapy, whereas renal involvement rarely is. Cyclophosphamide has also been
used in the management. Plasmapheresis is frequently useful in the management of
renal manifestations; however, many patients develop renal failure and
require dialysis or renal transplantation. Transplanted kidneys may develop
glomerulonephritis if anti-GBM antibodies are still present at the time of
Evaluate renal function: urea,
creatinine, and electrolytes, and optimize K+ if necessary. Evaluate
pulmonary function: pulse oximetry, chest radiograph, and pulmonary function
tests if indicated clinically. Consider perioperative corticosteroid ...