激素敏感型肾病综合征患儿糖皮质激素治疗Meta分析

目的:评价不同糖皮质激素治疗方案对预防糖皮质激素敏感型肾病综合征复发的作用及副作用.方法:以原发性肾病综合征(primary nephrotic syndrome,PNS)、糖皮质激素(glucocorticoid,GC)、皮质类固醇(corticosteroid,steroid)、泼尼松(predonisone)、甲泼尼龙(methypredonisolone)、地塞米松(dexamethasone)和儿童(children)等为主题词,通过电子检索MEDLINE(1963.1～2007.3)、elsevier(1997.1～2006.8)、OVID数据库(1993.1～2006.8)、Springer数据库(1994.1～2007.3),Cochrane对照实验登记处(Cochrane图书馆,2006,2期)、Cochrane肾脏专业登记组(2006年8月)、EMBASE(1980.1～2007.3)和中国期刊全文数据库(1994.1～2007.3)等,同时辅以手工检索并从参考文献中筛选,包括会议资料和学位论文.尽可能全面地收集GC应用治疗儿童(3月～18岁)PNS的临床随机对照或半随机对照实验,对符合要求的文献进行质量评估,用Review Manager 4.2软件对结果进行合并统计分析,计算治疗组相对于对照组的PNS复发及副作用的优势比(odds ratio,OR),评价不同治疗方案的作用及副作用.结果:本次评价中共纳入12篇随机对照实验(randomized controlled trial,RCT).总样本量为868例,其中5篇比较初发病例诱导缓解阶段的治疗2个月与大于3个月的疗效.应用GC 8周与12周或超过12周比较,在12～24个月时12周组相对于8周组的复发风险比(RR)为0.70,95%可信区间(confidence interval,CI)为0.60～0.89,而无副作用(side effect,SE)的增加,差异有统计学意义,维持治疗的时间与复发风险(risk,R)之间存在负线性相关(r2=0.66,P=0.05).结论:(1)与对照组相比,GC对于初发NS患儿应用大于12周效果显著优于8周者,能够减少半年内复发率,最初GC应用时间较长者,较能减少复发的风险;(2)标准治疗方案与隔日治疗相比,能够减少副作用,总疗程大于1年与短疗程比,能够减少2年复发率.通过本系统评价,支持对于初次应用者,首先用足量激素12周,隔日应用,总疗程大于1年的方案.

Glucocorticoid administration in steroid sensitive nephriticsyndrome: a Meta-analysis

OBJECTIVE: To evaluate the benefits and toxicities of different corticosteroid regimes in preventing relapse in children with steroid sensitive nephrotic syndrome (SSNS). METHODS: MEDLINE (Jan. 1963-Mar. 2007), elsevier (Jan. 1997-Aug. 2006), OVID databank (Jan. 1993-Aug. 2006), Springer databank (Jan. 1994-March 2007), the Cochrane Controlled Trials Register (Cochrane Library, Issue Feb. 2006), Cochrane Renal Group Specialised Register (Jul. 2006), EMBASE (Jan. 1980-Mar. 2007) and CNKI (Jan. 1994-Mar. 2007) etc, were searched by the terms primary nephrotic syndrome, glucocorticoid, corticosteroid, steroid, predonisone, methypredonisolone, dexamethasone and children etc for the human clinical trials about glucocorticoid (GC) administration in primary nephrotic syndrome (PNS) (aged 3 months to 18 years), controlled or semi-controlled ones, including unpublished documents from scientific meetings and theses, and similar documents listed in the references of the above documents were also included. All the studies were evaluated strictly according to Jadad Standard, and the Meta-analysis were adopted. Review manager 4.2 software was used to analyze the data. The odds ratio was calculated for the relapse rate and side effect from the initial episode to the end of follow-up between the patients treated with corticosteroids and the controls. RESULTS: Totally 12 trials with 868 subjects meeting the criteria were included in this review. A Meta-analysis of 7 trials, which compared between 2 months of prednisone and 3 months or more in the first episode, showed that longer treatment duration significantly reduced the risk of relapse at 12-24 months (RR=0.70,95% CI:0.60-0.89),without an increase of side effect. There was a negative linear relationship between the duration of treatment and risk of relapse (r2 =0.66, P=0.05). CONCLUSION: (1) Children in their first episode of SSNS should be treated for at least 3 months of GC. The therapeutic effect of patients in the primary nephrotic syndrome treated with GC for 12 weeks was prior to that for 8 weeks, compared with that in the controls. It could reduce the relapse rate of half year, the longer treatment duration in the NS patients at the first relapse was, the lower relapse risk was.(2) Compared with alternative GC administration, standard GC administration can reduce the side effects; Course more than 1 year of GC administration can reduce the 2-year relapse rate. Hence in children who relapse frequently, multicentre, well-designed experiments should be adopted.