Current and future therapy of small vessel vasculitis of the kidney

Renal involvement, characterised histologically by crescentic glomerulonephritis, is the most potent clinical determinant of long-term outcome in ANCA-associated systemic vasculitis (AASV). The presence of autoantibodies against neutrophil granule constituents may be an important pathogenic factor. The duration and intensity of treatment of renal vasculitis with standard induction therapies (prednisolone and cyclophosphamide) have been clarified by the completion of a number of prospective clinical trials. Based on these, most patients with renal vasculitis should receive 3 months of pulsed intravenous or oral cyclophosphamide plus tailing doses of prednisolone, with switching to azathioprine plus prednisolone thereafter for a minimum of 2 years. Added to this therapeutic backbone are methotrexate, plasma exchange and mycophenolate mofetil, use of which has been addressed by further prospective trials, most of which have been conducted by the European Vasculitis Study Group. Additional therapies, such as intravenous immunoglobulin and antithymocyte globulin may be used in cases of resistant vasculitis and when cyclophosphamide is poorly tolerated. Newer biologic agents are now emerging and are being subjected to rigorous testing. Of these, monoclonal antibodies directed against TNFa (a central cytokine in AASV pathogenesis) and CD20 (a specific B-cell marker) are proving most promising. This review will put these various therapeutic approaches into the context of renal vasculitis, with emphasis on a practical approach to management.