前瞻性比较普乐可复与环磷酰胺诱导治疗Ⅴ型伴Ⅳ型狼疮性肾炎的疗效  

Randomized controlled trial of tacrolimus versus intravenous cyclophosphamide in the induction therapy of class Ⅴ plus Ⅳ lupus nephritis

作　　者：章海涛[1] 胡伟新[1] 谢红浪[1] 曾彩虹[1] 陈惠萍[1] 刘志红[1] 黎磊石[1] 

机构地区：[1]南京军区南京总医院解放军肾脏病研究所,南京210002

出　　处：《肾脏病与透析肾移植杂志》2006年第6期508-514,共7页Chinese Journal of Nephrology,Dialysis & Transplantation

摘　　要：目的：前瞻性比较普乐可复（FK506）与环磷酰胺（CTX）联合激素诱导治疗Ⅴ型合并Ⅳ型（Ⅴ＋Ⅳ型）狼疮性肾炎LN）的临床疗效。方法：经肾活检诊断为Ⅴ＋Ⅳ型活动性、女性LN患者37例，平均年龄（30．0±9．8）岁，尿蛋白定量≥2．0g／d，血清白蛋白〈3．0g／dl，随机分为两组，分别给予口服FK506[FK506组，n=19，起始剂量0．1ms／（kg·d）]或CTX静脉冲击治疗（CTX组，n=18）（0．5～1．0g／m^2BSA，1／月×6月），同时口服泼尼松[起始剂量0．6mg/（ks·d）]，其中17例接受甲基泼尼松龙静脉冲击治疗。主要评价指标为治疗6个月完全缓解率（CR，定义为尿蛋白定量〈0．4g／24h，尿红细胞正常范围，无管型尿及白细胞尿，血清白蛋白≥3．5g／dl，SCr正常或上升不超过正常范围15％，无肾外狼疮活动），次要观察指标为治疗6个月部分缓解率（PR）和有效率（CR＋PR）。结果：（1）临床疗效：有31例患者完成6个月诱导期治疗，其中FK506组15例，CTX组16例；6例退出治疗，CTX组2例，FK506组4例。FK506组4例患者获得CR（26．7％），10例患者PR（66．7％），而CTX组仅1例CR（6．3％）、7例PR（43．8％）。FK506组治疗有效率明显高于CTX组（93．3％vs50％，P=0．015）。两组患者治疗后SLE-DAI、血清白蛋白、补体较前有显著改善，但血尿及抗dsDNA抗体的阳性率无明显改变；FK506组平均尿蛋白较治疗前显著减少，而CTX组较治疗前无明显下降；（2）FK506剂量浓度与不良反应：FK506诱导治疗剂量在0．086—0．091mg/（kg·d），平均谷浓度水平为6．6～8．1ng／ml。4例获得CR的患者FK506浓度在6．9～10．2ng／ml，10例PR患者血药浓度平均为（8．1±3．3）ng／ml。在此剂量下治疗6个月，未见肾小管间质损害。FK506组不良反应的发生率（肝酶升高、上消化道不适、白细胞减少、感染、脱发、月经紊乱等）低�Objective：To evaluate the efficacy and safety of tacrolimus （FK506） as the induction therapy in patients with class Ⅳ plus Ⅳ lupus nephritis （LN）. Methodology： Thirty-seven female patients diagnosed class Ⅴ ＋ Ⅳ LN （ according to ISN/RPS 2003 classification criteria） were randomly assigned to either FK506 0. 1 mg/（ kg· d） for 6 months （ n = 19） or intravenous cyclophosphamide （CTX） 0. 5 - 1.0 g/m^2 BSA monthly for 6 months （ n = 18） in addition to corticosteroids. The primary end point was complete remission （CR） at 6 months （ defined as a value of proteinuria 〈0. 4 g/24h with normal urinary sediment, serum albumin ≥3. 5 g/dl and a normal value of serum creatinine or no more than 15% above the base-line values）. A secondary end point was partial remission （PR） and remission at 6 months. Results： 1 ） Clinical efficacy： 31 patients （ K506 group = 15, CTX group = 16） completed the 6 months induction therapy. The remission occurred in 14 out of 15 patients in the FK506 group and 8 out of 16 patients in the CTX group （ P = 0. 015）. There were 4 patients （26. 7% ） in the FK506 group and 1 patient （6. 3% ） in the CTX group that achieved CR （ P 〉 0. 05 ）. The improvements in SLE-DAI, serum albumin and serum complement were similar in both groups, but there was no change of urine RBC and anti-dsDNA. The average proteinuria of post-treatment was significantly decreased in the FK506 group while with no improvement in the CTX group. 2） Dosage of FK506 and adverse effects： The inducement dosage of FK506 was 0. 086-0. 091 mg/（ kg· d） and the average trough blood concentration was 6. 6 - 8. 1 ng/ml. No damage in the renal tubular function was found under this dosage. 5 patients dropped out because of adverse effects （2 in the CTX group, 3 in the FK506 group） and one had no follow-up in FK506 group. The adverse effects of infection, temporary GPT/ GOT rise, upper gastrointestinal symptoms, leucopenia and irregular menstruation/amen

关 键 词：普乐可复 环磷酰胺 狼疮性肾炎 诱导治疗 不良反应 

分 类 号：R593.242[医药卫生—内科学]