Laboratory Studies
The most important requirement in the diagnosis of antineutrophil cytoplasmic antibody (ANCA)–associated disease is a high index of suspicion. Rapid diagnosis is essential for organ preservation. Laboratory studies include the following:
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Complete blood cell count (CBC) with differential: Results are most likely normal, but anemia may be present if the patient has kidney failure or is bleeding from the gastrointestinal tract. Eosinophilia of 13% or greater is suggestive of eosinophilic granulomatosis with polyangiitis (EGPA).
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Serum electrolytes, BUN, creatinine, lactate dehydrogenase (LDH), creatine phosphokinase (CPK), and liver function tests: The most common abnormality is an increased serum creatinine level. However, the level can be normal at presentation. Tissue enzyme (ie, LDH, CPK) levels may be elevated if the amount of inflammation is significant enough to result in myalgias.
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Urinalysis with microscopy: Proteinuria is almost always present but is rarely greater than 2-3 g in 24 hours. Microscopic hematuria is invariably present and may be the only clue to renal disease at presentation. The presence of red cell casts indicates glomerular inflammation and is a very helpful clue.
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Erythrocyte sedimentation rate: Although a nonspecific finding, the rate is usually elevated with active disease.
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C-reactive protein: Levels are elevated and correspond with disease activity.
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Antinuclear antibody (ANA) titer: The ANA titer result is not positive in patients with ANCA-associated disease. A high ANA titer should direct the diagnosis toward systemic lupus erythematosus.
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ANCA with ELISA subtyping: More than 80% of patients with microscopic polyangiitis are ANCA positive, and most of these demonstrate pANCA with MPO specificity. Of patients with granulomatosis with polyangiitis, 90% are ANCA positive and most have cANCA with PR3 specificity, especially in pulmonary involvement. However, ANCA type and specificity is not pathognomonic for each of these clinical syndromes because some patients with granulomatosis with polyangiitis are pANCA positive and some patients with microscopic polyangiitis are cANCA positive. Simon and colleagues investigated the presence of anti-pentraxin 3 (PTX3) autoantibodies (aAbs) in the sera of antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) patients and found that anti-PTX3 aAbs were present in nearly 40% of patients studied, including in patients without detectable MPO and PR3 ANCA. [8]
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Cryoglobulins: The symptoms of cryoglobulinemia are very similar to those of ANCA-related disease. However, in persons with ANCA-related diseases, the cryoglobulin titer result should be negative.
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Hepatitis profile: ANCA-associated disease is not associated with hepatitis. However, hepatitis B is associated with polyarteritis nodosa and hepatitis C is associated with mixed cryoglobulinemia.
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Urine and serum protein electrophoresis: Perform this in any middle-aged or elderly person presenting with rapidly progressive glomerulonephritis to exclude the presence of light-chain disease or overt multiple myeloma as a cause of the clinical findings.
Imaging Studies
A kidney ultrasound scan should be done to rule out obstructive uropathy in any patient with acute kidney injury. In patients with rapidly progressive glomerulonephritis, ultrasonography is done to establish the presence of 2 functioning kidneys prior to a percutaneous kidney biopsy.
Procedures
Because the sensitivity and the specificity of ANCA testing for pauci-immune glomerulonephritis is only 80-90%, kidney biopsy is recommended in patients with rapidly progressive glomerulonephritis to establish a definite diagnosis and to determine the severity of the disease. Kidney biopsy specimens show a diffuse, proliferative, necrotizing glomerulonephritis with crescent formation. However, the initiation of therapy should not be delayed for biopsy results to be obtained.
