他克莫司联合糖皮质激素治疗特发性膜性肾病的临床研究

2017-06-06 13:09徐毅芳徐莹
中国现代医生 2017年12期
关键词:他克莫司糖皮质激素

徐毅芳 徐莹

[摘要] 目的 觀察他克莫司联合糖皮质激素治疗特发性膜性肾病的疗效。 方法 选择2012 年12月~2014年12月于我院住院治疗的特发性膜性肾病患者120例,随机分为观察组和对照组,每组各60例,两组均予常规治疗和对症治疗。观察组同时联合他克莫司联合糖皮质激素治疗,治疗后比较两组的临床疗效以及比较两组患者尿蛋白、血清白蛋白、血肌酐水平治疗前后的变化。 结果 观察组治疗后未缓解3例,对照组治疗后未缓解18例。观察组治疗后的总缓解率(95.00%)显著高于对照组(70.00%),组间疗效比较有统计学差异(P<0.05)。两组治疗前尿蛋白、血清白蛋白、血肌酐水平比较无统计学差异(P>0.05);治疗后两组尿蛋白水平显著降低,血清白蛋白显著升高,差异有统计学意义(P<0.05);且观察组患者治疗后尿蛋白水平显著低于对照组,血清白蛋白显著高于对照组(P<0.05)。但两组患者血肌酐水平治疗前后以及组间比较未见明显差异(P>0.05)。 结论 他克莫司联合糖皮质激素治疗特发性膜性肾病疗效显著,可以显著改善肾功能,值得推广和应用。

[关键词] 特发性膜性肾病;他克莫司;糖皮质激素;血肌酐

[中图分类号] R692 [文献标识码] B [文章编号] 1673-9701(2017)12-0122-03

[Abstract] Objective To observe the efficacy of tacrolimus combined with glucocorticoid in the treatment of idiopathic membranous nephropathy. Methods 120 patients with idiopathic membranous nephropathy who were hospitalized in our hospital from December 2012 to December 2014 were selected. 120 cases of idiopathic membranous nephropathy were randomly divided into the observation group and the control group, with 60 cases in each group. Both groups were given routine treatment and symptomatic treatment. The observation group was treated with tacrolimus combined with glucocorticoid. After treatment, the clinical efficacy was compared between the two groups, and changes of urinary protein, serum albumin and serum creatinine were compared before and after the treatment. Results In the observation group, 3 cases were not remission after the treatment and 18 cases were not remission in the control group after treatment. The total remission rate(95.00%) in the observation group after the treatment was significantly higher than that in the control group(70.00%), and the difference in the efficacy between groups was statistically significant(P<0.05). There were no statistically significant differences in urinary protein, serum albumin and serum creatinine before the treatment between the two groups(P>0.05); after treatment, the levels of urine protein were significantly decreased, and serum albumin was significantly increased in both groups. The differences were statistically significant(P<0.05); and the level of urinary protein in the observation group was significantly lower than that in the control group after the treatment, and serum albumin was significantly higher than the control group. There was statistically significant difference between the two groups(P<0.05). However, there was no significant difference in serum creatinine level before and after treatment and between the two groups(P>0.05). Conclusion Tacrolimus combined with glucocorticoid in the treatment of idiopathic membranous nephropathy has a significant efficacy, which can significantly improve the renal function, and is worthy of promotion and application.

[Key words] Idiopathic membranous nephropathy; Tacrolimus; Glucocordicoid; Serum creatinine

特发性膜性肾病(idiopathic membranous nephropathy,IMN)约占膜性肾病(membranous nephropathy,MN)的 2/3,是中老年原发性肾病综合征患者常见的病理类型,高峰年龄为50~60岁[1-2]。糖皮质激素为治疗IMN的常用药物,但单用激素不能明显降低尿蛋白,不推荐单独应用[3-5]。他克莫司(tacrolimus,TAC)是一种新型强效免疫抑制剂,其作用机制虽与环孢素类似,但免疫抑制作用是环孢素的数十倍甚至百倍[6]。本研究旨在探讨他克莫司与糖皮质激素联合应用治疗特发性膜性肾病的疗效,现报道如下。

1 资料与方法

1.1一般资料

选择2012年12月~2014年12月于我院住院治疗的特发性膜性肾病患者120例,患者治疗前3个月内未使用过糖皮质激素或免疫抑制剂,均签署知情同意书,排除严重的肝、肾功能不全,股骨头坏死、活动性消化性溃疡、药物过敏者及妊娠或哺乳期女性。年龄20~70岁,平均(41.3±7.8)岁,平均病程(5.1±1.2)年,合并肾小球硬化13例。120例特发性膜性肾病患者随机分为观察组和对照组,每组各60例,两组患者的一般资料比较,差异无统计学意义(P>0.05),具有可比性。

1.2 治疗方法

两组患者根据血压、血脂情况针对性选用血管紧张素转换酶抑制剂、血管紧张素II受体拮抗剂、羟甲基戊二酰辅酶 A 还原酶抑制剂等药物。当血清白蛋白低于20 g/L 时加用低分子肝素钠抗凝,预防血栓形成。两组均口服泼尼松片,起始剂量为 0.75 mg/(kg·d),口服8~12 w 后开始进行减量,每2周减 5 mg,6 周后每月减 5 mg,3 个月后每月减 2.5 mg,减至 15 mg/维持治疗不超过 3 个月,此后每月减 2.5 mg,减至10 mg维持治疗。观察组同时联合他克莫司治疗,每日予他克莫司30 mg,服用8周后每 2 周每日用量减少5 mg,维持剂量为每日 5~10 mg。每月检测 1 次他克莫司的血药浓度,要求6 个月内将血药浓度维持在 5~10 μg/L,根据血药浓度调整用药剂量,但不能超过 0.15 mg/(kg·d)治疗。两组总疗程为12个月。

1.3 疗效评价

完全缓解为水肿消失,24 h 尿蛋白定量<0.3 g,血清白蛋白>35 g/L,肾功能正常;部分缓解为水肿减轻,24 h尿蛋白定量下降>50%,血清白蛋白30~35 g/L,肾功能好转或无变化;未缓解为水肿无改善,24 h尿蛋白定量下降<50%,血清白蛋白<30 g/L,肾功能恶化[7]。

1.4 统计学方法

数据分析采用SPSS20.0统计分析软件,计量资料采用t检验,计数资料采用χ2检验,P<0.05表示差异具有统计学意义。

2 结果

2.1 两组临床疗效比较

见表1,观察组治疗后未缓解3例,对照组治疗后未缓解18例。观察组治疗后的总缓解率(95.00%)顯著高于对照组(70.00%),组间疗效比较有统计学差异,差异具有统计学意义(P<0.05)。

2.2 两组患者尿蛋白、血清白蛋白、血肌酐水平治疗前后比较

见表2。两组治疗前尿蛋白、血清白蛋白、血肌酐水平比较无统计学差异(P>0.05);治疗后两组尿蛋白水平显著降低,血清白蛋白显著升高,差异有统计学意义(P<0.05);且观察组患者治疗后尿蛋白水平显著低于对照组,血清白蛋白显著高于对照组,两组组间比较,差异有统计学意义(P<0.05),但两组患者血肌酐水平治疗前后以及组间比较未见明显差异(P>0.05)。

2.3 不良反应

两组患者治疗期间未见明显不良反应。

3 讨论

特发性膜性肾病约占膜性肾病的 2/3,临床上约 80%的特发性膜性肾病患者表现为肾病综合征,超过40%的特发性膜性肾病患者可进展至终末期肾病[8-15]。

目前国内对存在大量蛋白尿的膜性肾病患者的传统标准治疗方案是糖皮质激素联合环磷酰胺(cyclophosphamide,CTX)冲击治疗,但 CTX副作用较多,严重影响患者疾病的预后。

糖皮质激素为治疗肾病综合征的常用药物,但研究显示,无论是短期还是长期,单用激素均不能缓解特发性膜性肾病患者的尿蛋白水平,也不能降低患者进入终末期肾病的风险,故不推荐单独应用[16-23]。他克莫司为新型免疫抑制药,可较好地调节患者的免疫功能,抑制 T 细胞激活、增殖及具有免疫放大效应的作用,且不良反应较少,目前广泛应用于器官移植和自身免疫性疾病的治疗[24-26]。临床许多研究也证实,他克莫司可减少蛋白尿,提升血浆白蛋白指数,有效恢复患者实验室指标,控制患者蛋白尿水平[27-28]。刘国建等[29]将53例经肾穿刺活检术后确诊的特发性膜性肾病患者分为他克莫司组(A组)和环磷酰胺组(B组),治疗后,他克莫司组与环磷酰胺组患者治疗后血清白蛋白明显上升,24 h尿蛋白定量明显下降,但他克莫司组较环磷酰胺组变化更显著,差异具有统计学意义(P<0.05),证实他克莫司联合糖皮质激素治疗特发性膜性肾病疗效好,且短期疗效可能优于环磷酰胺。本研究结果也证实了上述观点,观察组治疗后的总缓解率(95.00%)显著高于对照组的70.00%,差异具有统计学意义(P<0.05)。且观察组患者治疗后尿蛋白水平显著低于对照组,血清白蛋白显著高于对照组,差异具有统计学意义(P<0.05),与杨瑞衡等[30]报道的观点是相符的,说明他克莫司联合糖皮质激素治疗特发性膜性肾病疗效显著,可以显著改善肾功能,值得推广和应用。

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(收稿日期:2016-11-06)

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