- Rapidly deteriorating renal function, with or without hemoptysis and pulmonary shadowing on chest radiograph.
- Hematuria and proteinuria on urine dipstick and erythrocyte casts and/or dysmorphic erythrocytes on urine microscopy.
- Circulating antibodies directed against the glomerular basement membrane (GBM).
- Renal biopsy showing focal necrotizing glomerulonephritis with linear deposition of immunoglobulin.
Anti-glomerular basement membrane disease is a rare but well-characterized cause of glomerulonephritis, with an incidence of 1 case per million per year in white populations. All ages can be affected, but the peak incidence is in the third decade in young men and in the sixth and seventh decades in either sex. Lung hemorrhage occurs more often in younger patients, and isolated glomerulonephritis is more common in older patients. The disease is defined by the presence of pathogenic anti-GBM antibodies directed against the NC1 domain of the α3 chain of type IV collagen [α3(IV)NC1], a component of selected basement membranes including those of glomeruli and pulmonary alveoli. These cause focal necrotizing glomerulonephritis and result in widespread crescent formation on renal biopsy; clinically, the result is rapidly progressive glomerulonephritis. When this occurs in association with pulmonary hemorrhage, the condition is known as Goodpasture's syndrome.
The disease occurs in genetically susceptible individuals exposed to an environmental trigger. The HLA type strongly influences susceptibility; HLA types DR15 and DR4 predispose to disease, while HLA DR7 and DR1 are protective.
Environmental factors are involved in both triggering the disease and influencing its clinical presentation. Several reports describe clusters of cases, suggesting that an infective or other exogenous agent is involved in the pathogenesis, but no specific cause has been identified. Cigarette smoking has an important influence on the extent of lung injury, with pulmonary hemorrhage affecting almost all current smokers and being almost exclusively confined to this group. Lung hemorrhage following hydrocarbon exposure has also been described. In addition, genetic factors affect disease susceptibility.
Patients often have a history of malaise, arthralgia, and weight loss, but these features are generally far milder than in other causes of focal necrotizing glomerulonephritis, such as antineutrophilic cytoplasmic antibody (ANCA)-associated systemic vasculitis. Anemia is common, and may be symptomatic even in patients with minimal hemoptysis. The principal clinical symptoms relate either to pulmonary hemorrhage or to the development of renal failure. The severity of pulmonary hemorrhage varies and can range from minor hemoptysis to life-threatening hemorrhage with respiratory failure. Typically, hemoptysis is intermittent at the outset and can occur spontaneously or can be precipitated by intercurrent infections or fluid overload. There is a poor correlation between the severity of hemoptysis and the quantity of pulmonary blood loss, with other clinical signs being variable. These include inspiratory crackles and bronchial breathing, with patients often tachypnoeic and cyanosed. Historically hemoptysis has been the most common presenting feature, but its incidence is decreasing with the reduced prevalence of cigarette smoking. It now occurs in about 50% of ...