丙种球蛋白联合糖皮质激素和环磷酰胺治疗特发性膜性肾病的有效性及安全性

Efficacy and safety of gamma globulin therapy combined with steroids and cyclophosphamide in patients with idiopathic membranous nephropathy

目的研究丙种球蛋白冲击联合糖皮质激素和环磷酰胺(CTX)治疗表现为肾病综合征的特发性膜性肾病(IMN)的有效性和安全性。方法回顾性分析第二军医大学附属长海医院肾内科2008年7月至2012年6月,尿蛋白>3.5 g/24 h,经肾活检并结合临床诊断为IMN患者临床资料。初始治疗采用丙种球蛋白冲击[0.4 g/(kg·d)×3 d]继之给予足量泼尼松[1 mg/(kg·d),最大剂量80 mg/d,联合CTX(0.75 g/m2体表面积,1次/月,共6次)冲击治疗,足量泼尼松治疗2个月后规律减量,入组为丙球组,共19例;按照年龄、性别及尿蛋白程度匹配的方式,入组同期诊断为IMN单纯采用糖皮质激素联合CTX(用法与丙球组相同)的患者19例,设为对照组。总疗程均为6个月。观察两组治疗6个月后的疗效及不良反应。组间计量资料比较采用t检验,组间计数资料比较采用卡方检验。治疗随访结果以部分缓解为观察终点,以Kaplan-Meier生存曲线表示。结果治疗6个月时,丙球组4例(4/19,21.1%)患者完全缓解,9例(9/19,47.4%)患者部分缓解,有效率为68.5%(13/19);对照组3例(3/19,15.8%)患者完全缓解,8例(8/19,42.1%)患者部分缓解,有效率为57.9%(11/19)。丙球组达到部分缓解的平均时间较对照组短[(2.54±1.39)月与(3.73±1.50)月],差异有统计学意义(P<0.05)。两组患者在治疗过程均未发生严重不良反应,丙球组感染的发生率低于对照组,差异有统计学意义(P<0.05)。结论丙种球蛋白联合糖皮质激素和环磷酰胺治疗特发性膜性肾病大多能有效减轻蛋白尿,感染并发症少。

Objective A clinical control study was conducted to evaluate the efficacy and safety of gamma globulin pulse therapy combined with steroids and cyclophosphamide （CTX ） in idiopathic membranous nephropathy （IMN ） patients manifesting as nephrotic syndrome.Methods IMN patients retrospectively collected in our hospital from July 2008 to June 2012,were diagnosed according to urinary protein over 3.5 g/24 h,renal biopsy,and clinical features.The initial treatment was pulse gamma globulin [0.4 g /（kg·d） ×3 d]followed by enough prednisone [1 mg/（kg·d）,maximum dose 80 mg/d]plus pulse CTX （0.75 g/m2 BSA,1 time /month ×6 times ）.After 2 months of enough dose therapy, prednisone was regularly reduced.These patients entered the gamma globulin group of 19 cases.the The control group also contained nineteen IMN patients matched by age,gender,and urinary protein level,who were treated with only oral prednisone plus pulse CTX.The whole course of treatment lasted 6 months in each group,and then the efficacy and safety were evaluated.The test data were analyzed with SPSS 16.0 statistical software.As for quantitative data expressed as mean ±standard deviation,differences between the two groups were compared with t test,while for count data expressed as number of cases （percentage）, differences between the two groups were compared with the chi-square test.The endpoint result of follow-up＆amp;nbsp;after treatment was partial remission,which was expressed with Kaplan-Meier survival curve,and differences between the two groups were compared with log-rank test.A difference was considered statistically significant when P value was less than 0.05.Results After 6 months of treatment,the gamma globulin group showed complete remission in 4 cases （4/19,21.1%）,and partial remission in 9 cases （9/19,47.4%）,with an effective rate of 68.5% （13/19）,while the control group showed complete remission in 3 cases （3/19, 15.8%）,and partial remission in 8 cases （8/19,42.1%）,with an effective rate of57.9%（11/19）.The gamma globulin group achieved the partial remission in an average time less than the control group [（2.54 ±1.39）months vs （3.73 ±1.50）months],which was statistically significant （χ2 =4.378,P〈0.05 ）.No severe adverse events were observed during the treatment.The incidence of infection was significantly lower in gamma globulin group than in control group （χ2 =4.378,P〈0.05 ）.Conclusions The treatment of gamma globulin therapy combined with steroids and CTX was effective in reducing proteinuria of most IMN patients,and was with few infectious complications.