小剂量他克莫司联合糖皮质激素对中等量蛋白尿IgA肾病的临床疗效回顾

Clinical efficacy of low-dose tacrolimus combined with glucocorticoid on IgA nephropathy with moderate proteinuria: a report of 64 cases

目的研究小剂量他克莫司(tacrolimus,TAC)联合糖皮质激素在中等量蛋白尿IgA肾病中的临床疗效和安全性。方法回顾筛选2012年1月至2015年1月在我院肾科就诊并结合临床和肾活检确诊为中等量蛋白尿(1.0~3.5 g/24 h)IgA肾病患者64例。根据治疗方案将患者分为小剂量TAC+激素组[n=34,他克莫司0.02~0.05 mg/(kg·d),分两次口服,血药谷浓度维持在3~5 ng/m L,强的松起始剂量0.5 mg/(kg·d)(最大剂量不超过40 mg/d)口服]和激素组[n=30,强的松起始剂量1 mg/(kg·d)(最大剂量不超过70 mg/d)口服]。收集分析患者治疗前及治疗后1、3、6个月时的临床资料,并记录发生的不良反应。选取24 h尿蛋白定量、血肌酐(Scr)、血白蛋白(ALB)为主要临床疗效评价指标。结果两组患者治疗前各临床指标基线值对比差异均无统计学意义(P>0.05)。两组患者在治疗6个月后24 h尿蛋白定量均显著下降,血白蛋白显著升高,与治疗前比较差异均有统计学意义(P<0.05)。小剂量TAC+激素组在治疗1、3、6个月时24 h尿蛋白定量的降低值与激素组比较差异具有统计学意义(P<0.05);但在完全缓解率和总有效率上两组间各时间点比较差异均无统计学意义(P>0.05)。不良反应比较:在对白细胞、血红蛋白及血小板的监测中未发现加用小剂量TAC出现的骨髓抑制现象,也没有明确的感染事件发生。其他不良反应:小剂量TAC+激素组新发血糖升高4例,肝功能损害3例,胃肠道反应1例,反复口腔溃疡1例,激素组新发血糖升高5例,肝功能受损4例,胃肠道反应2例,两组比较差异无统计学意义(P>0.05)。两组患者治疗6个月时血肌酐及e GFR分别与治疗前比较,差异均无统计学意义(P>0.05)。结论在中等量蛋白尿IgA肾病的治疗中,小剂量起始、低血药浓度维持的TAC+激素的治疗方案依然有效,对比单足量激素组表现出了更好的降低患者蛋白尿水平的作用,且没有增加不良反应,但并不能带来临床完全缓解率和总有效率的上升。

Objective To investigate the clinical efficacy and safety of low-dose tacrolimus （TAC） in combination of glucocorticoid in treatment of IgA nephropathy with moderate proteinuria. Methods A total of 64 patients IgA nephropathy with moderate proteinuria （ 1.0 - 3.5 g per 24 h） diagnosed by renal biopsy and clinical data who admitted in our department from January 2012 to January 2015 were enrolled in this study. According to therapeutic schemes, the patients were divided into low-dose TAC ＋ glucocorticoid group [ n = 34, TAC 0.02 - 0.05 rag/（ kg · d）, orally twice per day, with trough concentration being maintained at 3 -5 ng/mL; oral administration of prednisone with an initial dose of 0.5 mg/（ kg · d） and maximal dose not exceeding 40 mg/d] and hormone group E n = 30, oral administration of prednisone with an initial dose of 1 mg/（kg·d） and maximal dose not exceeding 70 mg/d]. The clinical data before treatment and at 1,3 and 6 months after treatment were collected and analyzed, and their adverse reactions were also recorded. The 24- hour urinary protein, serum creatinine （Scr） and serum albumin （ALB） were selected as primary endpoints.Results There were no significant differences between 2 groups in their clinical baseline data （P 〉 O. 05 ）. The 24-hour urinary protein was obviously decreased while ALB increased in both 2 groups in 6 months after treatment （ P 〈 0.05 ）, and the reduction was more notably in the low-dose TAC ＋ glucocorticoid group at 1,3 and 6 months after treatment than the hormone group （ P 〈 0.05 ）. No statistically differences were seen in complete remission rate and total effective rate between the 2 groups at each time point （ P 〉 0. 05 ）. As for adverse reactions, in the monitoring of leukocyte, hemoglobin and platelet, no phenomenon of bone marrow suppression and infection was observed in the low-dose TAC group. There were 4 cases of blood glucose elevation, 3 cases of liver function impairment, 1 case of gastrointestinal reaction and 1 case of recurrent oral ulcer occurred in the low-dose TAC ＋ glucocorticoid group. But for the hormone groups, the numbers of cases were increased to 5,4 and 2 cases respectively. Though there was no case of recurrent oral ulcer in the latter group, no statistical difference was seen between the 2 groups （P 〉 0.05 ）. Both groups had no significant difference in Scr level and eGFR in 6 months after treatment compared with the values before treatment （ P 〉 0.05 ）. Conclusion In the treatment of lgA nephropathy with moderate proteinuria, low-dose TAC ＋ glucocorticoid is more efficiently in reduction of urinary protein than simple use of enough hormones, and has no effect on the increase of side effects. But it shows no benefits in higher clinical complete remission rate and total effective rate.