Medical Care
Therapy for antineutrophil cytoplasmic antibody (ANCA)–associated disease consists of a combination of corticosteroids and cyclophosphamide. Treatment with steroids alone results in a 3-fold increase in the risk of relapse compared with combination therapy. The only predictor of kidney survival is the serum creatinine value at the time of diagnosis. Therefore, a high index of suspicion is imperative to establish the diagnosis quickly and to institute treatment as soon as possible. Kidney failure requiring dialysis is not a contraindication to treatment. Many patients can be removed from dialysis for an extended period (18 mo to 2 y).
The regimen used by the Glomerular Disease Collaborative Network at the University of North Carolina at Chapel Hill [9, 10] is as follows:
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Administer methylprednisolone at 7 mg/kg/d intravenously (not to exceed 1 g) for 3 days, followed by oral prednisone at 1 mg/kg/d (not to exceed 80 mg) for 3 weeks, and then oral prednisone at 2 mg/kg every other day (not to exceed 120 mg) for 3 months. This dose is decreased by 25% every 4 weeks until the patient stops taking prednisone.
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Administer cyclophosphamide either intravenously or orally. Intravenous therapy is initially administered at a dose of 0.5 g/m2, and the oral dose is 2 mg/kg. Both are adjusted according to a 2-week leukocyte nadir count (goal 3000-4000/µL). The maximum intravenous dose is 1 g/m2. Oral and intravenous cyclophosphamide appears to be equally efficacious. However, this remains an area of controversy, particularly in the case of granulomatosis with polyangiitis, for which some advocate oral therapy. The advantage to using the intravenous preparation is that the risk of cumulative toxicity is lower because a lower total dose is used.
Another protocol, which has been used widely and with success in Europe, is the substitution of azathioprine for cyclophosphamide after a 3-month induction period. Azathioprine is administered at 2 mg/kg orally in a single daily dose. This is continued for 6-12 months.
Methotrexate has been substituted for cyclophosphamide in the initial treatment of granulomatosis with polyangiitis for mild disease and has been used for treatment after initial induction therapy with cyclophosphamide in more severe disease. [11]
Plasmapheresis may be a beneficial addition to therapy for patients who present with severe kidney failure (serum creatinine > 6 mg/dL) or those whose disease progresses despite treatment.
Rituximab may improve kidney outcomes in ANCA-associated vasculitis; in addition to anti–B-cell therapy, therapy directed at T cells may improve kidney outcome, according to a study conducted by Berden et al. [12] A systematic literature review of a total of 171 patients with eosinophilic granulomatosis with polyangiitis (EGPA) treated with rituximab found greater benefit in ANCA-positive patients than in ANCA-negative patients. [13]
Other medications have been used in an attempt to attain a remission, such as intravenous immunoglobulin, antithymocyte antibody, and humanized monoclonal antibody to CD4 and CD25. None of these therapies has been well studied. They appear in the literature as case reports.
Consultations
Nephrology consultation should be obtained as early as possible in suspected cases of rapidly progressive glomerulonephritis.
Long-Term Monitoring
Close follow-up care is extremely important in any patient with active vasculitis. The therapies for ANCA-associated vasculitides are not proven in large, randomized, controlled trials but are the standard of care according to consensus. The same can be said for the definitions of relapse, response, and treatment failure.
The following criteria were established by Nachman et al before they performed a randomized control trial comparing immunosuppression regimens in patients diagnosed with microscopic polyangiitis or isolated pauci-immune rapidly progressive glomerulonephritis only (patients with granulomatosis with polyangiitis were excluded). [10]
Remission criteria are as follows:
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Stabilization or improvement of renal function (as measured by serum creatinine value), resolution of hematuria, and resolution of extrarenal manifestations of systemic vasculitis
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Persistence of proteinuria not considered indicative of persistent disease activity
Remission by therapy is defined as achievement of remission while still receiving immunosuppressive medication or corticosteroids (prednisone dose or equivalent of >7.5 mg/d)
Treatment resistance is defined as follows:
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Progressive decline in renal function with the persistence of an active urine sediment
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Persistence or new appearance of any extrarenal manifestation of vasculitis despite immunosuppressive therapy
Relapse criteria include at least one of the following:
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Rapid rise in serum creatinine concentration, accompanied by an active urine sediment
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Renal biopsy findings demonstrating active necrosis or crescent formation
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Hemoptysis, pulmonary hemorrhage, or new or expanding nodules without evidence for infection
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Active vasculitis of the respiratory or GI tracts as demonstrated by findings from endoscopic biopsy
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Iritis or uveitis
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New mononeuritis multiplex
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Necrotizing vasculitis identified based on findings from biopsy specimen of any tissue
