多靶点诱导治疗增殖性和膜性狼疮肾炎的有效性和安全性临床研究

摘要

目的 探讨多靶点诱导治疗增殖性和膜性狼疮肾炎的有效性和安全性.方法 将32例患者随机分为多靶点治疗组和环磷酰胺(cyclophosphamide,CTX)组.诱导期初定24周,若24周内未达完全缓解,诱导期延长至36周.2组患者均采用静脉甲基泼尼松龙冲击后口服泼尼松治疗.多靶点治疗组采用霉酚酸酯1 000mg/d(体质量低于50 kg的患者750mg/d),分2次,早、晚餐前口服;他克莫司起始剂量4mg/d(体质量低于50 kg的患者3mg/d),分2次,早、晚餐前(间隔12 h)口服,服药7d后开始检测血药浓度,目标血药谷浓度达到5～7 ng/ml.CTX组CTX首次剂量0.75 g/m2,此后根据具体情况调整在0.5～1.0 g/m,每4周1次.所有患者入选前2周内均在B超引导下行经皮肾穿刺术,肾组织常规行HE、PAS、PASM、Masson染色,半定量评分肾组织狼疮活动性病理指数及慢性化病理指数.治疗36周后常规检测血清巨细胞病毒抗体.当患者出现细菌感染迹象时,根据临床需要选择胸部CT、B超、细菌培养等检查,以明确感染部位及细菌种类.结果 多靶点治疗组24周完全缓解率显著高于CTX组(62.50％比18.75％,P＜0.01),36周完全缓解率显著高于CTX组(68.75％比31.25％,P＜0.05).Kaplan-Meier生存函数分析显示多靶点治疗组较CTX组更短时间获得部分缓解和完全缓解(P＜0.01).多靶点治疗主要的不良反应为CMV感染(占43.75％).结论 多靶点诱导治疗增殖性和膜性狼疮肾炎有效性优于传统的CTX治疗,虽然巨细胞病毒感染风险较高,但无需特殊处理.%Objective To investigate the efficacy and safety of treatment of both proliferative and membranous lupus nephritis with multi-target therapy.Methods Thirty-two patients were randomly divided into multi-target therapy group and cyclophosphamide(CTX) group.The induction course of treatment was initially set to 24 weeks,and it was prolonged to 36 weeks if subjects did not achieve complete remission within 24 weeks.Two groups of patients were treated with intravenous methylprednisolone after oral prednisone therapy.Tacrolimus(TAC) was given at 4 mg/d,and mycopholatemofetil(MMF) 1.0 g/d.CTX was given monthly 0.75 g/m2 BSA.All enrolled patients were subjected to renal puncture 2 weeks before therapy.Lupus activity index(AI) and chronic index(CI) were estimated by semi-quantitative scores in the renal tissue.After 36 weeks of treatment,serum cytomegalovirus(CMV) antibody was tested.When patients had signs of bacterial infection,B ultrasound,chest CT,and bacterial culture were performed to identify the site and bacterial species of infection according to the clinical needs.Results The complete remission rate in the multi-target therapy group was significantly higher than that in the CTX group after both 24 weeks(62.50％ vs.18.75％,P＜ 0.01) and 36 weeks (68.75 ％ vs.31.25 ％,P ＜ 0.05),respectively.Kaplan-Meier analysis showed that subjects in the multi-target group achieved both partial and complete remission earlier than in the CTX group(P＜0.01).CMV infection(43.75 ％) was the major adverse effect of multi-target therapy.Conclusions Multi-target therapy is superior to CTX therapy for both proliferative and membranous lupus nephritis.Although the risk of CMV infection is high,the patient is well tolerated.