小剂量他克莫司联合雷公藤多苷治疗激素抵抗性肾病综合征随机对照研究

Low-dose tacrolimus combined with tripterygium in treatment of steroid-resistant nephrotic syndrome: a prospective randomized controlled trial

目的观察小剂量他克莫司(TAC)联合雷公藤多苷(TW)治疗激素抵抗性肾病综合征(SRNS)的临床疗效和安全性。方法经肾活检并结合临床诊断为系膜增生性肾炎(MesPGN)和局灶节段性肾小球硬化(FSGS)、经泼尼松[1 mg/(kg.d),最大60 mg/d]治疗3个月无效的患者,随机分为2组。小剂量TAC+TW组:TAC首次使用0.05 mg/(kg.d),分2次、间隔12 h于餐后2 h服用,服药3 d后检测TAC浓度,维持血药浓度1.5～4 ng/ml;同时加用TW治疗剂量60 mg/d,分3次餐前口服。TW组:单用TW,治疗剂量60 mg/d,分3次餐前口服。观察各组的疗效、不良反应以及TAC的浓度变化。结果(1)符合入组条件的SRNS患者共20例,小剂量TAC+TW组11例,TW组9例。入组基线年龄、性别分布、发病时间、血压、24h尿蛋白定量、血清白蛋白、肌酐、胆固醇、三酰甘油、空腹血糖、肾脏病理类型及服用泼尼松时间等无明显统计学差异。(2)小剂量TAC+TW组治疗1个月后尿蛋白开始下降,随访至12个月时有8例完全缓解(72.7%),2例部分缓解(18.2%),1例无效(9.1%),总有效率(90.9%)。而TW组同样治疗1个月后尿蛋白开始减少,但随访至12个月时仅有2例完全缓解(22.2%),部分缓解4例(44.5%),无效3例(33.3%),总有效率(66.7%)。随访至终点小剂量TAC+TW组完全缓解率高于TW组。(3)小剂量TAC+TW组治疗后患者血浆蛋白明显升高,治疗至6个月时血浆蛋白基本恢复至正常水平;而TW组血浆蛋白升高却不明显。两组患者血肌酐水平治疗前后无明显改变。(4)不良反应的发生率两组之间无明显差异。结论小剂量TAC+TW能有效减少SRNS患者蛋白尿,临床缓解率较高;并且患者耐受性好,是治疗SRNS的有效方法。

Objective To observe the clinical efficacy and safety of low-dose tacrolimus（TAC） combined with tripterygium（TW） in treatment of steroid-resistant nephrotic syndrome（SRNS）.Methods The patients,who were diagnosed with mesangial proliferative glomerulonephritis（MesPGN） and focal segmental glomerulosclerosis（FSGS） by biopsy and failed to respond to a 3 month treatment with prednisone（1 mg/,maximum 60 mg/d,were randomly divided into 2 groups（TAC＋TW group and TW group）.Initially TAC＋TW group took TAC 0.05 mg/（kg·d） 2 h after meal at a 12 h interval;the plasma TAC level was examined after 3 days and was kept at 1.5-4 ng/ml;meanwhile,TW was given at 60 mg/d before meal.TW group only took TW（60 mg/d before meal）.The efficacy,adverse reactions and plasma TAC levels were observed in each group.Results（1） Totally 20 patients met the recruitment criteria, including 11 in the TAC＋TW group and 9 in the TW group.The age,sex,time of onset,blood pressure,24 h urine protein,serum albumin,creatinine,cholesterol,triglyceride,fasting blood glucose,renal pathology types and period of prednisone use were similar between the two groups.（2） In TAC＋TW group the urine protein began to decrease one month later;12 months later,8 cases had complete remission（72.7%）,2 had partial remission（18.2%）,and 1 was ineffective（9.1%）,with a total effective rate of 90.9%.In TW group the urine protein also began to decrease one month later;12 months later only 2 cases had complete remission（22.2%）,4 had partial remission（44.5%）,and 3 were ineffective（33.3%）,with a total effective rate of 66.7%.（3）In TAC ＋ TW group the plasma protein was significantly higher than that before treatment;the plasma protein recovered to normal level after 6 month treatment.However,there was no significant increase in TW group.The pre-and post-treatment serum creatinine levels were similar between the two groups.（4） The incidence rates of adverse reactions were not significantly different between the two groups.Conclusion Low dose TAC combined with TW can effectively decrease proteinuria in patients with SRNS,generating a higher rate of clinical remission;meanwhile,the patients have a good tolerance and less adverse reactions.