Crescentic glomerulonephritis associated with myeloperoxidase-antineutrophil-cytoplasmic antibodies: first report on the efficacy of primary anti-TNF-alpha treatment.

Abstract

We report on successful induction of remission in a patient with necrotizing crescentic glomerulonephritis associated with myeloperoxidase-antineutrophil-cytoplasm antibodies by primary use of the anti-tumor necrosis factor (TNF)-alpha chimeric monoclonal antibody infliximab in combination with corticosteroids only. The standard treatment containing cyclophosphamide has reduced the former high mortality from systemic vasculitides. However, the toxicity of this alkylating agent limits its long-term use. As TNF-alpha has been shown to play a central pathogenic role in vasculitis as well as in crescentic glomerulonephritis, anti-TNF-alpha treatment in combination with cyclophosphamide has been found to be effective in therapy-resistant vasculitis. Previous reports on TNF-alpha-blocking therapies without additional cyclophosphamide did not include patients with active and severe crescentic glomerulonephritis. As our patient refused cyclophosphamide, he was given four infusions of infliximab (4 mg/kg on weeks 0, 2, 6 and 10) and methylprednisolone pulses (1 g on days 1-3), followed by daily oral prednisolone (starting with 2 mg/kg and tapering down to 5 mg daily within 3 months). After 12 weeks, control biopsy demonstrated lack of active glomerular inflammation while initially reduced renal function (creatinine 271 versus 172 mol/l, clearance 26 versus 62 ml/min) and proteinuria (2.4 versus 1.0 g/d) improved. Under remission maintenance therapy with azathioprine and prednisolone, the patient showed no relapses during a 1-year follow-up. Finally we demonstrate that there might be patients with crescentic glomerulonephritis who do not require therapy with alkylating substances and that less toxic agents such as the TNF-alpha-blocking monoclonal antibody infliximab could play a role in future primary treatment of crescentic glomerulonephritis.