他克莫司联合糖皮质激素治疗特发性膜性肾病的临床疗效观察

Clinical efficacy of tacrolimus combined with glucocorticoids for idiopathic membranous nephropathy

目的观察他克莫司联合小剂量糖皮质激素治疗表现为肾病综合征的特发性膜性肾病的有效性及安全性。方法回顾性分析2011年1月至2014年6月于厦门大学附属中山医院肾内科住院并经肾活检明确诊断为特发性膜性肾病患者20例,给予他克莫司剂量0.05~0.1 mg·kg^(-1)·d^(-1),联合口服糖皮质激素泼尼松0.5 mg·kg^(-1)·d^(-1)(或甲泼尼龙0.4 mg·kg^(-1)·d^(-1))。分别于治疗后的3、6、12、18个月观察患者的血常规、尿常规、24 h尿蛋白定量、血白蛋白、血脂、肝肾功能、血糖的变化情况以及不良反应发生情况,同时监测他克莫司的血药浓度(谷浓度)。结果 20例患者在随访的各个阶段,监测其血肌酐、尿素氮、尿酸、丙氨酸氨基转移酶、糖指标的波动,与治疗前比较差异均无统计学意义(P>0.05)。治疗前24 h尿蛋白定量为(6.74±3.08)g,血白蛋白为(23.57±4.51)g/L;与治疗前比较,随访3、6、12、18个月时24 h尿蛋白定量显著下降[(3.69±2.65)g、(2.48±2.21)g、(2.19±2.10)g、(1.26±1.42)g,P<0.05],血白蛋白水平显著升高[(33.16±6.87)g/L、(36.96±6.63)g/L、(37.30±7.62)g/L、(39.84±4.31)g/L,P<0.05]。随访18个月时,9例患者达到完全缓解,8例患者达到部分缓解,总缓解率为85%(17/20);治疗期间未发生严重不良反应。结论他克莫司联合小剂量糖皮质激素治疗表现为肾病综合征的特发性膜性肾病患者,疗效好,不良反应小。

Objective Although idiopathic membranous nephropathy （IMN） is a common cause of adult-onset nephrotic syndrome, its treatment remains controversial. Recent studies show tacrolimus is effective in the treatment of IMN. This study was performed to evaluate the efficacy and safety of tacrolimus （TAC） combined with glucocorticoids in patients with IMN. Methods Twenty patients with biopsy-proven IMN were collected in this retrospective study. TAC was given at 0. 05-0. 1 mg. kg-1· day-1 initially, in combination with oral administration of glucocorticoids （prednisone 0. 5 mg. kg- 1·day- 1 or methylprednisolone 0. 4 nag- kg- 1· day- 1 ）. The primary outcome was the remission rate, whereas the secondary outcomes included the changes in serum albumin levels and daily urinary protein levels, and adverse events. Results After treatment with TAC combined with glucocorticoids for 3 months, the albumin levels had a significant improvement [（23. 57 ± 4. 51） g/L vs. （33. 16 ± 6. 87） g/L, P〈0. 05], and the proteinuria had a significant decrease [（6. 74± 3. 08）g vs. （3. 69 ± 2. 65） g, P〈0.05]. At the 6th month post-therapy, the albumin levels were significantly improved [（23.57 ± 4. 51） g/L vs. （36. 96 ± 6. 63） g/L, P〈0. 051, and the proteinuria was significantly decreased [（6.74± 3. 08） g vs. （2. 48 ±2. 21） g, P〈0. 051. At the 12th month post-therapy, the albumin levels were significantly improved [（23. 57± 4. 51） g/L vs. （37. 30 ± 7. 62） g/L, P〈0. 051, and the proteinuria was significantly decreased [（6. 74 ±3. 08） g vs. （2. 19 ± 2. 10） g, P〈0. 051. At the end of the 18-month therapy, the albumin levels were significantly improved [（23. 57 ± 4. 51） g/L vs. （39. 84 ± 4. 31） g/L, P〈0. 05], and the proteinuria was significantly decreased [（6. 74±3. 08） g vs. （1.26 ±1.42） g, P〈0. 05]. After treatment for 18 months, complete remission （CR） was achieved in 45 % （9/20） of the patients and partial remission （PR） in 40% （8/20）, yielding a final response rate of 85%（17/20）. Two patients experienced relapses during the follow-up period of 12 month. There were no significant changes in ereatinine, transaminase and glucose in blood. The patients had no serious adverse reactions during the treatment. Conclusions In this study, treatment with tacrolimus showed a good efficacy with mild adverse reactions in patients with IMN.