普乐可复与环磷酰胺诱导治疗Ⅳ型狼疮性肾炎的疗效比较  

Tacrolimus versus intravenous cyclophosphamide in the induction therapy of diffuse proliferative 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501-507,共7页Chinese Journal of Nephrology,Dialysis & Transplantation

摘　　要：目的：比较观察口服普乐可复（FKS06）与环磷酰胺静脉冲击（IVC）联合激素诱导治疗Ⅳ型狼疮性。肾炎（LN）的疗效及安全性，探讨FKS06合适的治疗剂量与血药浓度范围。方法：经肾活检诊断为Ⅳ—G型（2003年ISN／RPS分类）活动性、女性LN患者34例，平均年龄（27．1±9、9）岁，尿蛋白定量≥2．0g／d，血清白蛋白〈3．0g／dl，随机分为FKS06组[n=17，起始剂量0．1mg／（k·／d）]和IVC组（n=17，0．5～1．0g／m^2BSA，1／月×6月），同时口服泼尼松（0．6mg／kg·d），其中22例患者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（PR）率和有效率（CR＋PR）。结果：（1）临床疗效：治疗6个月FKS06组和IVC组的有效率分别为94．1％和82．4％，FK506组有11例患者获得CR（11／17，64．7％），高于IVC组（7／17，41.2％）（P=0．303）；FKS06组出现PR的时间明显短于IVC组[（1．9±1．2）月vs（3．2±1．8）月，P=0．034]，而两组获得CR的时间分别为（4．0±1.3）月和（5.0±1．2）月；两组患者SLE—DAI、尿蛋白水平、血尿、血清白蛋白、补体C3、C4水平及A—dsDNA阳性率较治疗前均有显著改善；（2）FK506的剂量和浓度：FK506的剂量平均为0．08～0．09mg／（kg·d），血药浓度为5．7～7.1ng／ml；获得CR的患者血药浓度平均为（8．1±3．9）ng／ml，PR的患者为（5．2±2.7）ng／ml，其中3例血药浓度低于5ng／ml的患者亦获得CR；（3）不良反应：FK506组肝酶升高、感染等发生率低于IVC组，未见白细胞减少、月经紊乱，而短暂SCr升高、高血压、高血糖、脱发等并发症高于IVC组，但无统计学�Objective：To assess the efficacy and safety of tacrolimus （FKS06） as the induction therapy in patients with diffuse proliferative lupus nephritis （LN） and to explore the dosing of FK506 and its suitable blood concentration. Methodology：Thirty-four female patients diagnosed class Ⅳ-G LN （according to ISN/RPS 2003 classification criteria） were randomly assigned to either FK506 0. 1 mg/（kg·d） for 6 months （n = 17 ） or intravenous cyclophosphamide （IVC） 0. 5 - 1.0 g/m^2 BSA monthly for 6 months （n = 17） in addition to corticosteroids. The primary end point was complete remission （CR） at 6 months （ defined as a value of proteinuria 〈 0. 4 g/24hr 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： The remission occurred in 16 out of 17 patients （94. 1% ） in the FK506 group and 14 out of 17 patients （82. 4% ） in the IVC group. There were 64. 7% in the FK506 group and 41.2% in the IVC group that achieved CR （P =0. 303）. The average time to reach PR in the FK506 group was significantly less than that in the IVC group （ 1.9 ± 1.2 vs 3.2 ± 1.8 months, P = 0. 034） while the time to reach CR was 4. 0 ± 1.3 and 5.0 ± 1.2 months, respectively. The improvements in SLE-DAI, proteinuria, urine RBC, serum albumin, serum complement and antisDNA were similar in both groups. 2） Dosage and trough blood level of FK506： The average dosage of FK506 was 0. 08 -0. 09 mg/（kg·d） and trough blood level was 5. 7 -7. 1 ng/ml. Those who achieved CR with high blood level of 8. 1 ±3.9 ng/ml and those of PR were 5.2 ±2. 7 ng/ml. 3 patients whose blood level less than 5. 0 ng/ml also achieved CR. 3 ） Adverse effects： In the FK506 group, the adverse effects of infection, temporary GPT/GOT rise, leucopenia, irregular menstruation were lower than that in the IVC group.

关 键 词：狼疮性肾炎 普乐可复 环磷酰胺 诱导治疗 不良反应 

分 类 号：R593.242[医药卫生—内科学]