Hama Taketsugu, Nakanishi Koichi, Ishikura Kenji, Ito Shuichi, Nakamura Hidefumi, Sako Mayumi, Saito-Oba Mari, Nozu Kandai, Shima Yuko, Iijima Kazumoto, Yoshikawa Norishige
Department of Pediatrics, Wakayama Medical University, Wakayama, Japan.
Department of Child Health and Welfare (Pediatrics), Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa, 903-0215, Japan.
BMC Nephrol. 2018 Sep 10;19(1):223. doi: 10.1186/s12882-018-1033-z.
Eighty percent of children with steroid-sensitive nephrotic syndrome (SSNS) relapse within 2 years and 40-50% patients show frequently-relapsing nephrotic syndrome (FRNS). Patients showing a relapse within 6 months after initial remission are at high risk of FRNS. Since frequent prednisolone treatment for FRNS induces severe prednisolone side effects, development of a treatment to prevent patients from shifting to FRNS is desirable. Mizoribine is an immunosuppressive drug with fewer side effects than prednisolone. Recent studies reported the efficacy of high-dose mizoribine in children with FRNS.
METHODS/DESIGN: We conduct a multicenter, open, randomized controlled trial to investigate the efficacy and safety of standard prednisolone plus high-dose mizoribine therapy in children with SSNS showing a relapse within 6 months after an initial remission. Patients are allocated to either standard prednisolone alone treatment group, or standard prednisolone plus high-dose mizoribine group. For the former group, mizoribine is administered at a dose of 10 mg/kg/day once daily and continued for 2 years. The primary endpoint is the duration to frequent relapse.
The results provide important data on use of high-dose mizoribine to prevent SSNS patients from shifting to FRNS. Since blood concentrations of mizoribine have not been investigated in detail until now, there is a possibility that mizoribine is underestimated in favor of other immunosuppressive drugs. In future, high-dose mizoribine therapy may lead to prevention of relapse in children at high risk of FRNS, and to decreased total dose of prednisolone.
UMIN000005103 , (Prospectively registered 1st March 2011).
80%的激素敏感型肾病综合征（SSNS）患儿在2年内复发，40 - 50%的患者表现为频繁复发型肾病综合征（FRNS）。初次缓解后6个月内复发的患者发生FRNS的风险很高。由于频繁使用泼尼松龙治疗FRNS会引发严重的泼尼松龙副作用，因此开发一种预防患者转变为FRNS的治疗方法是很有必要的。咪唑立宾是一种免疫抑制药物，其副作用比泼尼松龙少。最近的研究报道了高剂量咪唑立宾对FRNS患儿的疗效。
方法/设计：我们开展一项多中心、开放性、随机对照试验，以研究标准泼尼松龙联合高剂量咪唑立宾疗法对初次缓解后6个月内复发的SSNS患儿的疗效和安全性。患者被分配到单独使用标准泼尼松龙治疗组或标准泼尼松龙加用高剂量咪唑立宾组。对于前一组，咪唑立宾以每日10 mg/kg的剂量给药，每日一次，持续2年。主要终点是频繁复发的持续时间。
研究结果为使用高剂量咪唑立宾预防SSNS患者转变为FRNS提供了重要数据。由于迄今为止尚未详细研究咪唑立宾的血药浓度，有可能咪唑立宾相较于其他免疫抑制药物被低估。未来，高剂量咪唑立宾疗法可能会预防FRNS高危儿童的复发，并减少泼尼松龙的总剂量。
UMIN000005103，（2011年3月1日前瞻性注册）
