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Treatment of young patients with lupus nephritis using calcineurin inhibitors

World Journal of Nephrology 2012年第6期1卷 177-183页

作者： Hiroshi Tanaka Kazushi Tsuruga Tomomi Aizawa-Yashiro Shojiro Watanabe tadaatsu imaizumi Department of School Health Science Faculty of Education Hirosaki University Hirosaki 036-8562 Japan Department of Pediatrics Hirosaki University Hospital Hirosaki 036-8562 Japan imaizumi Department of Vascular Biology Hirosaki University Graduate School of Medicine Hirosaki 036-8562 Japan

Recent advances in the management of lupus nephritis, together with earlier renal biopsy and selective use of aggressive immunosuppressive therapy, have contribut-ed to a favorable outcome in children and adolescents with systemic lupus erythematosus （SLE）. Neverthe-less, we believe that a more effective and less toxic treatment is needed to attain an optimal control of the activity of lupus nephritis. Recent published papers and our experiences regarding treatment of young patients with lupus nephritis using calcineurin inhibitors are re-viewed. Although it has been reported that intermittent monthly pulses of intravenous cyclophosphamide （IVCY） are effective for preserving renal function in adult pa-tients, CPA is a potent immunosuppressive agent thatinduces severe toxicity, including myelo- and gonadal toxicity, and increases the risk of secondary malig-nancy. Thus, treatment for controlling lupus nephritis activity, especially in children and adolescents, remains challenging. Cyclosporine A （CsA） and tacrolimus （Tac） are T-cell-specific calcineurin inhibitors that prevent the activation of helper T cells, thereby inhibiting thetranscription of the early activation genes of interleu-kin （IL）-2 and suppressing T cell-induced activation of tumor necrosis factor-α, IL-1β and IL-6. Therefore, both drugs, which we believe may be less cytotoxic, are attractive therapeutic options for young patients with lupus nephritis. Recently, a multidrug regimen of prednisolone （PDN）, Tac, and mycophenolate mofetile （MMF） has been found effective and relatively safe in adult lupus nephritis. Since the mechanisms of action of MMF and Tac are probably complementary, multidrug therapy for lupus nephritis may be useful. We propose as an alternative to IVCY, a multidrug therapy with mizoribine, which acts very similarly to MMF, and Tac, which has a different mode of action, combined with PDN for pediatric-onset lupus nephritis. We also believe that a multidrug therapy including CsA and

关键词： Calcineurin inhibitor Cyclosporine A Lupus nephritis Multidrug therapy Systemic lupus erythema-tosus Tacrolimus

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