Indications for Testing
Laboratory testing is used to:
- Diagnose patients with symptoms of anti-GBM disease (particularly rapid, progressive renal disease that exists alone or in combination with pulmonary disease)
- Identify organ dysfunction associated with anti-GBM disease
- Monitor the efficacy of treatment
Serologic testing for anti-GBM antibodies is usually performed using a number of immunoassays; however, enzyme-linked immunosorbent assays (ELISAs), multiplex bead-based, and indirect immunofluorescence (IIF) assays are the most common test methods used in clinical laboratories. Due to the rapidly progressive nature of glomerulonephritis in anti-GBM disease, fast turnaround of serologic testing is essential for timely treatment initiation. However, serologic testing is not recommended as a standalone diagnostic tool, and a small percentage of patients may have antibodies that are undetectable by current methods. Kidney biopsy should be performed to confirm the results of serologic testing unless contraindicated.
Antineutrophil Cytoplasm Antibody Testing
Up to 30% of patients with anti-GBM disease are also antineutrophil cytoplasm antibody (ANCA) positive. ANCA testing should be performed concurrently with anti-GBM testing. Patients with anti-GBM disease who are ANCA positive have been found to be more susceptible to relapse than patients positive only for anti-GBM antibodies. Although this susceptibility has not been firmly established, patients positive for ANCAs may warrant additional monitoring. ANCA testing may also support the diagnosis of another form of vasculitis or rule out other causes of rapidly progressive glomerulonephritis.
Kidney Tissue Testing
Tissue examination is the gold standard for anti-GBM disease diagnosis.
Deposited Antibody Testing
Direct immunofluorescence testing of kidney tissue for anti-GBM immunoglobulin G (IgG) is very sensitive for anti-GBM disease. Linear deposits of IgG are generally visible; however, these deposits may be difficult to distinguish if there is severe inflammation and architectural disruption, and may arise for reasons other than anti-GBM disease.
The vast majority of patients with anti-GBM disease will exhibit glomerular crescents of uniform age, the hallmark of anti-GBM disease, on histopathologic examination. Infiltrating neutrophils and lymphocytes and periglomerular inflammation may also be observed, among other features.
A variety of nonspecific tests may be useful in anti-GBM disease. A CBC frequently reveals anemia in patients with anti-GBM disease. Creatinine and blood urea nitrogen (BUN) are likely to be elevated in response to kidney damage. Urinalysis may also show red blood cells (RBCs), blood, and protein.
C-reactive protein (CRP) is generally the preferred marker of inflammation and is usually elevated in anti-GBM disease. If CRP testing is not available, erythrocyte sedimentation rate (ESR) testing may be used.
Anti-GBM antibody concentrations generally decline with effective treatment, and increased antibody concentrations following remission may indicate relapse. A period of 6 months without detectable anti-GBM antibodies is suggested before kidney transplant due to the risk of recurrence if a transplant is performed in a patient who still has anti-GBM antibodies. However, definitive guidance is lacking on the appropriate methods for anti-GBM antibody testing for monitoring purposes (eg, direct immunofluorescence testing vs serologic testing), and information on the limitations of these tests in the context of monitoring is also scarce. Given the rare nature of anti-GBM disease, as well as the growing recognition of variant and atypical forms of anti-GBM disease, clinicians should be aware that the use of anti-GBM antibody testing for monitoring purposes may present challenges.