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目的:比较观察口服普乐可复(FK506)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FK506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FK506组[n=17,起始剂量0·1mg/(k·/d)]和IVC组(n=17,0·5~1·0g/m2BSA,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FK506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);FK506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,但无统计学差异。结论:FK506是诱导治疗Ⅳ型LN的一种有效的免疫抑制剂,起效快,不良反应较小。
OBJECTIVE: To compare the efficacy and safety of FK506 with intravenous cyclophosphamide (IVC) and hormone therapy in the treatment of type Ⅳ lupus nephritis (LN). To explore the appropriate therapeutic dose and concentration range of FK506 . Methods: The activity of type Ⅳ-G (2003 ISN / RPS classification) was diagnosed by renal biopsy. There were 34 female LN patients with the mean age of (27.1 ± 9.9) years and the urinary protein quantitation of ≥ 2.0 g / d , Serum albumin <3. 0g / dl, were randomly divided into FK506 group [n = 17, the initial dose of 0 · 1mg / (k · / d)] and IVC group (n = 17,0 · 5 ~ 1.0g / m2BSA, 1 / month × 6 months), while oral prednisone (0.6mg / kg · d), of which 22 patients received 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 extra-renal lupus activity), the secondary outcome measure was 6-month partial remission (PR) rate and effective rate (CR + PR). Results: (1) The clinical curative effect: The effective rates of FK506 group and IVC group were 94.1% and 82.4% respectively after 6 months treatment, and 11 cases (11/17, 64.7%) in FK506 group , Higher than that of IVC group (7 / 17.41 · 2%) (P = 0.303). The time of PR in FK506 group was significantly shorter than that of IVC group [(1.9 ± 1.2) months vs (3.2 ± 1.8 months), P = 0. 034], while the time to CR in both groups was (4.0 ± 1.3) months and (5.0 ± 1.2) months respectively. The SLE- DAI, urinary protein level, hematuria, serum albumin, complement C3 and C4 levels and A-dsDNA positive rate were significantly improved compared with those before treatment; (2) The dose and concentration of FK506: the average dose of FK506 was 0.08-0 · The mean serum concentration of CR in patients receiving CR was (8.1 ± 3.9 · ng / ml), and the patients with PR were (09.9 mg / (kg · d) 5 · 2 ± 2 · 7) ng / ml. CR was also found in 3 patients with blood plasma concentrations less than 5ng / ml. (3) Adverse reactions: The incidence of liver enzymes in FK506 group was higher than that in IVC group , No leukopenia, menstrual disorders, and transient SCr increased, hypertension, hyperglycemia, hair loss and other complications higher than the IVC group, but no significant difference. Conclusion: FK506 is an effective immunosuppressive agent for induction of type Ⅳ LN with rapid onset and less adverse reactions.