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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0·1mg/(kg·d)]或CTX静脉冲击治疗(CTX组,n=18)(0·5~1·0g/m2BSA,1/月×6月),同时口服泼尼松[起始剂量0·6mg/(kg·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)低于CTX组,尤其是月经紊乱的发生率显著低于CTX组(5·6%vs38·9%,P=0·041);虽然血压升高、糖代谢异常等并发症高于CTX组,但两组间无统计学差异。结论:FK506诱导治疗Ⅴ型合并Ⅳ型病变的LN疗效明显优于CTX治疗,不良反应小。
Objective: To prospectively compare the clinical efficacy of prokake (FK506) and cyclophosphamide (CTX) combined with hormone therapy in the treatment of type Ⅴ with type Ⅴ (type Ⅳ) lupus nephritis LN. Methods: The V + Ⅳ type activity was diagnosed by renal biopsy. There were 37 female patients with LN (mean age 30.0 ± 9.8), urine protein≥2.0g / d, serum albumin <3.0g / dl were randomly divided into two groups and received oral FK506 [FK506 group, n = 19, initial dose of 0.1 mg / (kg · d)] or CTX vein impulse therapy (CTX group, n = 18) 5-1.0 g / m2 BSA, 1 / month × 6 months), while oral prednisone [initial dose 0.6 mg / (kg · d)], of which 17 cases were treated with methylprednisolone pulse therapy. The main evaluation index for the treatment of 6 months complete remission rate (CR, defined as urinary protein quantitation <0 · 4g / 24h, urinary red blood cells normal range, tubeless urine and leukocyturia, serum albumin ≥ 3.5g / dl, SCr Normal or up not more than 15% of the normal range, no renal lupus activity), the secondary outcome measure was 6-month partial response rate (PR) and effective rate (CR + PR). Results: (1) Clinical curative effect: 31 patients completed induction period of 6 months, including 15 cases in FK506 group and 16 cases in CTX group; 6 patients quit treatment, 2 cases in CTX group and 4 cases in FK506 group. Four of the four patients in the FK506 group had CR (26.7%) and PR (66.7%) in 10 patients, compared to only one CR (6.3%) and PR (43.8%) in the CTX group. FK506 treatment group was significantly higher than the CTX group (93.3% vs50%, P = 0.015). After treatment, SLE-DAI, serum albumin and complement were significantly improved in both groups, but the positive rates of hematuria and anti-dsDNA antibody did not change significantly. The average urinary protein in FK506 group was significantly lower than that before treatment, while CTX group (2) FK506 dose concentration and adverse reactions: the dose of FK506 induced treatment was 0.086-0.09 lmg / (kg · d), the average trough concentration level was 6.6-6.1ng / ml. The concentration of FK506 in 4 CR patients ranged from 6.9 ng / ml to 10.2 ng / ml, and the average plasma concentration of PR in 10 patients was (8.1 ± 3.3) ng / ml. At this dose for 6 months, there was no tubulointerstitial damage. The incidence of adverse reactions in FK506 group (elevated liver enzymes, upper gastrointestinal tract discomfort, leukopenia, infection, hair loss, menstrual disorders, etc.) was lower in the FK506 group than in the CTX group, especially in the CTX group (5.6 % vs38 · 9%, P = 0.041). Although the complications such as high blood pressure and abnormal glucose metabolism were higher than CTX group, there was no significant difference between the two groups. Conclusion: FK506 induced type Ⅴ with type Ⅳ lesions of LN was significantly better than the CTX treatment, adverse reactions.