Anti-GBM Antibody Disease Workup

Updated: Dec 19, 2019
  • Author: Agnieszka Swiatecka-Urban, MD, FASN, FAAP; Chief Editor: Craig B Langman, MD  more...
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Workup

Laboratory Studies

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  • Circulating anti-glomerular basement membrane (GBM) antibodies

    • The presence of anti-GBM antibodies is pathognomonic. However, approximately 10% of patients do not have identifiable circulating antibodies with conventional assays and serologic testing should not be the only diagnosis criteria and kidney biopsy should be performed in suspected cases. [10]

    • Detection of the anti-GBM antibodies is achieved by means of direct enzyme-linked immunoassay (ELISA). This test can be performed with less than 1 mL of blood. ELISA requires the use of native or recombinant human alpha-3 (type IV collagen) NC1 antigen as a substrate, which makes this method more sensitive and specific than others.

    • The specificity of the antibody can be confirmed with Western blotting.

    • False-negative rates are less than 5% and may occur in patients with low anti-GBM antibody titers or in some patients with Alport syndrome who develop anti-GBM disease after transplantation. A false-positive rate of less than 1% is related to the detection of antibodies directed against other chains of type IV collagen.

    • Indirect immunofluorescent staining is rarely performed and requires an experienced renal pathologist. This test is performed by incubating normal renal tissue with the patient's serum and then treating it with fluorescein-labeled anti–IgG. Immunofluorescence indicates of immunoglobulin G (IgG) deposition and is diagnostic. False-negative results are seen in 10-40% of patients. See the image below.

      Immunofluorescence staining for immunoglobulin (Ig Immunofluorescence staining for immunoglobulin (IgG) reveals diffuse, high-intensity, linear staining of the glomerular basement membrane in a patient with anti–glomerular basement membrane (GBM) disease. Courtesy of Glen Markowitz, MD, Department of Pathology, Columbia University.
  • Serum electrolytes and renal function

    • Renal function ranges from normal to rapidly deteriorating over a few weeks to months. Doubling of the serum creatinine level and halving of the glomerular filtration rate (GFR) within 3 months indicates rapidly progressive glomerulonephritis.

    • Electrolyte abnormalities, such as hyponatremia, hyperkalemia, hyperphosphatemia, and acidemia, may be seen with advanced disease.

  • Urine

    • Gross or microscopic hematuria may be present.

    • Urinalysis may reveal nephritic urinary sediment with dysmorphic RBCs and RBC casts.

    • Proteinuria is usually present, but protein levels are not in the nephrotic range.

  • Blood cells

    • A CBC count may reveal hypochromic microcytic anemia secondary to iron deficiency.

    • Mild thrombocytopenia may be detected.

  • Complements: The C3 level is below the reference range in 30-80% of pediatric patients.

  • Antineutrophilic cytoplasmic antibodies (ANCA)

    • ANCA are autoantibodies directed against constituents of the primary granules of neutrophils and the peroxidase positive lysosomes of monocytes.

    • ANCA is detectable in as many as 30% of patients with anti-GBM disease. Titers of ANCA and anti-GBM antibodies tend to be inversely related.

    • The detection of ANCA is clinically relevant in anti-GBM disease because patients with this disease are more likely to respond to therapy.

    • Besides having prognostic value in anti-GBM disease, ANCA is an important diagnostic marker in the ANCA associated small-vessel vasculitis, such as Wegener granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome, and some forms of drug-induced vasculitis (eg, thiouracil). These conditions are included in the differential diagnosis of anti-GBM disease. Therefore, patients presenting with acute glomerulonephritis with or without pulmonary hemorrhage are routinely tested for ANCA.

  • Sputum: Hemosiderin-laden macrophages indicate pulmonary hemorrhage.

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Imaging Studies

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  • Renal ultrasonography usually reveals kidneys of normal size, with no anatomic abnormalities.

  • When pulmonary hemorrhage is present, chest radiography may reveal alveolar infiltrates spreading from the hilum.

  • Chest CT scanning is more accurate than chest radiography for the diagnosis of pulmonary hemorrhage.

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Other Tests

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  • Results of pulmonary function tests are abnormal with pulmonary hemorrhage and may help in evaluating therapeutic effectiveness.

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Procedures

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  • Renal biopsy is not required for diagnosis if circulating anti-GBM antibodies are unequivocally present. However, histologic findings are an important guide to therapy and prognosis.

  • Most experts recommend renal biopsy unless the procedure is contraindicated.

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Histologic Findings

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  • During the active phase of the disease, cellular crescents are usually seen in the glomeruli. In advanced cases, fibrous (rather than cellular) crescents and tubulointerstitial involvement (eg, tubular atrophy, interstitial infiltrate, fibrosis) may be present. The lungs have intra-alveolar hemorrhages and are iron loaded. Vasculitis of the kidneys or lungs is uncommon but may be present in patients who are ANCA positive.

  • Under immunofluorescent microscopy, the finding of linear deposition of IgG along the glomerular capillaries and, occasionally, along the tubules is nearly pathognomonic. Only 2 other renal conditions are associated with linear glomerular IgG staining: diabetic nephropathy and fibrillary glomerulonephritis. Focal and interrupted linear deposits of IgG along the alveolar basement membrane may also be seen in anti-GBM disease. Electron microscopy reveals frequent breaks of the GBM.

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