他克莫司治疗乙型肝炎病毒相关性膜性肾病的随机对照临床试验  

Tacrolimus in the treatment of HBV associated membranous nephropathy： a randomized controlled trial

作　　者：万静芳[1] 卢晓梅[1] 唐雪莲[1] 李开斌[1] 林利容[1] 何娅妮[1] 李开龙[1] 

机构地区：[1]第三军医大学大坪医院野战外科研究所肾内科,重庆400042

出　　处：《中华肾脏病杂志》2015年第1期1-6,共6页Chinese Journal of Nephrology

基　　金：第三军医大学临床科研基金（2010XLC39）

摘　　要：目的 进行前瞻性、随机、对照临床试验,评估他克莫司联合恩替卡韦和小剂量糖皮质激素治疗乙型肝炎病毒相关性膜性肾病（Hepatitis B virus-associated membrane nephropathy,HBV-MN）的临床疗效.方法 入组患者38例,按随机数字表法分为试验组19例和对照组19例,试验组给予他克莫司（0.05 mg· kg-1·d-1）、小剂量激素（醋酸泼尼松,0.5 mg·kg-1·d-1）及恩替卡韦（0.5 mg/d）联合治疗,对照组接受恩替卡韦（0.5 mg/d）单一疗法,以完全缓解率及部分缓解率来评估患者疗效.结果 在治疗第6个月及12个月试验组总缓解率分别为88.89％、94.44％,但在对照组仅38.89％、58.82％,试验组观察到尿蛋白缓解更加明显.恩替卡韦可减少乙型肝炎病毒DNA（HBV-DNA）滴度,在治疗第3个月,入组患者肝功能均恢复正常.试验组有1例、对照组有2例因达到次要终点而退出本次试验.试验组有1例在他克莫司减量过程中尿蛋白复发.结论 他克莫司联合恩替卡韦和小剂量糖皮质激素治疗HBV-MN,能显著降低蛋白尿、保护肾功能,并能控制HBV-DNA的复制,是HBV-MN有效的治疗模式之一.Objective To conduct a prospective,randomly controlled trial,evaluating the combination of tacrolimus,corticosteroids and entecavir for the treatment of adult patients with biopsyproven hepatitis B virus-associated membrane nephropathy （HBV-MN）.Methods A total of 38 patients with biopsy-confirmed HBV-MN were randomized to the tacrolimus group （n=19） and the control group （n=19）.Patients in tacrolimus group received combination therapy of tacrolimus （0.05 mg·kg-1 · d-1）,corticosteroids （prednisone acetate,0.5 mg· kg-1 · d-1） and entecavir （0.5 mg/d）,whereas patients in control group received entecavir mono-therapy （0.5 mg/d）.The primary end point was the percentage of patients reaching complete remission （CR） or partial remission （PR）.Results The probability of remission in the treatment group was 88.89% and 94.44% after 6 and 12 months,but only 38.89% and 58.82% in the control group,respectively.The decrease in proteinuria was significantly greater in the treatment group.Entecavir was used for the treatment of hepatitis in all patients,which caused the disappearance of serum hepatitis B viral DNA（HBV-DNA） and the normalization of ALT and AST levels in 3 months.Notably,two patients in the control group and one patient in the treatment group reached the secondary end point.One patient in the tacrolimus-treated group showed a relapse during the taper period.Conclusion This treatment protocol not only can control the replication of HBV-DNA but also can reduce proteinuria and preserve renal function,it is one of useful therapeutic options for patients with HBV-MN.

关 键 词：他罗利姆 糖皮质激素类 肝炎病毒 乙型 肾小球肾炎 膜性 恩替卡韦 

分 类 号：R692[医药卫生—泌尿科学]