来氟米特联合中小剂量激素治疗IgA肾病的疗效观察  

Leflunomide combined with medium/low dose corticosteroids vs full dose of corticosteroids in treatment of IgA nephropathy

作　　者：闵璐琳 张敏芳[1] 车霞静[1] 牟姗[1] 曹励欧[1] 王琴[1] 戴慧莉[1] 方炜[1] 顾乐怡[1] 朱铭力[1] 王玲[1] 俞赞喆[1] 周文彦[1] 戚超君[1] 钱家麒[1] 倪兆慧[1] 

机构地区：[1]上海交通大学医学院附属仁济医院肾脏科,200127

出　　处：《中华肾脏病杂志》2016年第10期721-727,共7页Chinese Journal of Nephrology

基　　金：国家重点基础研究发展计划（973计划）（2012CB517602）;国家自然科学基金（81570604）;“十二五”国家科技支撑计划（2011BAI10B08）

摘　　要：目的比较来氟米特联合中小剂量激素与足量激素治疗IgA肾病的短期与长期疗效及安全性评估。方法研究人群18～65周岁，纳入标准eGFR≥30ml·min-1·（1．73m2）-1且24h尿蛋白量〉0．5g的原发性IgA肾病患者。所有人选患者经计算机随机进入来氟米特联合中小剂量激素组（LEF组）和单用激素组（激素组）；研究的主要终点为：（1）进入ESRD或透析治疗；（2）Ser升高超过基线值的50％；次要终点为蛋白尿缓解。结果完成随访的患者共90例，LEF组40例，激素组50例，基线24h尿蛋白量LEF组和激素组分别为2．00（1．10，2．88）g和1．87（1．13，3．08）g，两组患者尿蛋白在治疗6个月[分别为0．30（0．11，0．93）g，0．30（0．14，1．33）g]和12个月[分别为0．30（0．09，0．82）g，0．32（0．14，0．66）朗时较治疗前均有好转（P〈0．05）。激素组治疗后eGFR较治疗前升高[治疗前（80．39±28．56）、6个月（87．12±28．70）、12个月（88．20±30．26）ml·min-1·（1．73m2）-1，P〈0．05]，LEF组eGFR治疗前后差异无统计学意义[治疗前（87．63±27．35）、6个月（86．91±32．45）、12个月（90．06±30．00）ml·min-1·（1．73m2）-1，P〉0．05]，但治疗6个月及12个月时两组间比较尿蛋白、血肌酐、eGFR差异均无统计学意义（P〉0．05）。治疗期间两组不良反应发生率（LEF组9／40例，激素组11／50例）差异无统计学意义（P〉0．05）。平均随访79个月发现两组肾脏预后差异无统计学意义。Cox回归分析提示基线血肌酐及肾脏间质炎性细胞浸润程度是IgA肾病疾病进展的独立危险因素。结论来氟米特联合中小剂量激素对进展性IgA肾病的疗效与足量激素相当，治疗期间未增加不良事件发生率。Objective To compare the efficacy and safety of leflunomide （LEF） combined with medium/low dose eorticosteroids and full dose of corticosteroids in the treatment of IgA nephropathy. Method Primary IgAN patients diagnosed by renal biopsy with 18-65 years old and eGFR ≥30 ml· min-1·（1.73 m2）-1 and proteinuria 〉 0.5 g/24 h were enrolled in a prospective controlled clinical study. They were randomly divided into leflunomide combined with medium/low dose corticosteroids （LEF group） and corticosteroids alone （steroid group）. The primary outcomes were （1） end stage renal disease or dialysis （2） 50% increase in serum creatinine above the baseline. Secondary outcome was the remission of proteinuria. Results Ninety patients completed the follow-up. The 24- hour proteinuria at baseline were 2.00（1.10, 2.88） g and 1.87（1.13,3.08） g in LEF group and steroid group respectively. Compared with baseline, it was significantly decreased in both groups at 6 months [0.30（0.11, 0.93） g, 0.30（0.14, 1.33） g] and 12 months [0.30（0.09, 0.82） g, 0.32（0.14, 0.66） g], （P〈 0.05）. Estimated glomerular filtration rate （eGFR） at baseline, 6 months and 12 months were （80.39± 28.56）, （87.12±28.70） and （88.20±30.26） ml· min-1· （1.73 m2）-1. It was decreased in steroid group （P 〈 0.05）, while no significant difference was detected in LEF group[baseline （87.63 ±27.35）, 6 months （86.91±32.45）, 12 months （90.06±30.00） ml· min-1· （1.73 m2）-1, P 〉 0.05]. At 6 and 12 months, there was no significant difference in terms of 24- hour proteinuria, serum creatinine and eGFR （CKD-EPI） between groups （P 〉 0.05）. There was no statistically significant difference in adverse events between groups during the treatment （9/40 eases in LEF group and 11/50 eases in steroid group, P 〉 0.05）. The average follow-up was 79 months, and there was no difference in the renal prognosis between the two groups. Multivariate Cox regression analysis reveal

关 键 词：肾小球肾炎 IGA 糖皮质激素类 免疫抑制剂 预后 来氟米特 

分 类 号：R692.31[医药卫生—泌尿科学]