阿魏酸钠治疗糖尿病肾损害的系统评价

目的系统评价阿魏酸钠治疗糖尿病肾损害（DKD）的疗效与安全性。方法计算机检索Cochrane图书馆临床对照试验资料库（2008年第4期）、MEDLINE（1996～2008．12）、EMbase（1980—2008．12）、CBMdisc（1990～2008．12）、CNKI（1994—2008．12）和VIP（1989～2008．12），手工检索相关文献，纳入阿魏酸钠治疗糖尿病’肾损害的随机对照试验（RCT）。根据Cochrane评价员手册5．0版评估纳入研究的偏倚风险，采用RevMan5．0软件进行统计分析。结果纳入39个RCT，共2351例2型糖尿病损害患者。大部分研究方法学质量较低且样本含量较小，存在发生偏倚的高度风险，Meta分析显示：①肾功能指标：尿白蛋白排泄率[WMD=-42．92，95％CI（-52．61，-33．23）]、24h尿蛋白定量[WMD=-0．11，95％CI（-0．16，-0．05）]、尿素氮[WMD=-0．76，95％CI（-1．04，-0．46）]、血清肌酐[WMD=-8．38，95％CI（-11．81，-4．94）]，阿魏酸钠组均优于常规治疗组；②血糖指标：空腹m糖[WMD=-0．27，95％CI（-0．48，-0．06）]；餐后2h血糖[早期：WMD=-0．22，95％CI（-0．49，0．04）；临床期：WMD=-2．39，95％CI（-3．23，-1．54）]；糖化血红蛋白[WMD=-0．12，95％CI（-0．27，0．02）]；阿魏酸钠组在改善空腹血糖和临床期餐后2h血糖方面优于常规治疗组，但在改善糖化血红蛋白和早期餐后2h血糖方面与常规治疗组相当；③血压指标：收缩压[早期：WMD=-1．80，95％CI（-2-80，-0．81）；临床期WMD=-8．95，95％CI（-16．93，-0．96）]、舒张压[早期：WMD=-1．25，95％CI（-4．37，1．87）；临床期：WMD=-0．99，95％CI（-2．48，0．50）]、平均动脉压[WMD=-0．74，95％CI（-1．08，-0．40）]，阿魏酸钠组在改善收缩压和平均动脉压方面优于常规治疗组，但在改善舒张压方面与常规治疗组相当；④血脂指标：总胆困醇[WMD=-0．70，95％CI（-1．01，-0．39）]、甘油三酯[早期：WMD=-0．12，95％CI（-0．28，0．04）；临床期：WMD=-0．96，95％CI（-1．49，-0．43）]、高密度脂蛋白胆同醇[WMD=0．14，95％CI（0．06，0．22）]，阿魏酸钠组对改善总胆同醇、高密度脂蛋白胆同醇及临床期甘油三酯方面优于常规治疗组，但在改善早期甘油乏酯方面与常规治疗组相当；⑤内皮素（ET）指标：血ET[WMD=-18．72，95％CI（-25．20，-12．23）]、尿ET[WMD=-8．55，95％CI（-10．92，-6．18）]，阿魏酸钠在改善血、尿ET方面优于常规治疗组。⑥不良反应：8个研究仅提及阿魏酸钠治疗期间无不良反应或毒副作用，1个研究报道出现轻度且短暂性头痛，1个研究报道出现头晕乏力，未见严重不良反应事件。结论现有临床证据显示，阿魏酸钠治疗DKD有一定疗效且相对安全。但由于纳入的研究问存在异质性和发生偏倚的高度可能性，势必影响结果的论证强度，期待更多高质量的随机双肓对照试验提供高质量的证据。

Sodium Ferulate for Diabetic Kidney Disease: A Systematic Review

Objective To assess the efficacy and safety of Sodium ferulate for diabetic kidney disease. Methods Based on the principles and methods of Cochrane systematic reviews, we searched the Cochrane Central Register of Controlled Trials （Issue 4, 2008）, MEDLINE （1996 to December 2008）, EMbase （1980 to December 2008）, CBMdisc （1990 to December 2008）, CNKI （1994 to December 2008） and VIP （1989 to December 2008）. And we also hand searched relevant journals and conference proceedings. We evaluated the risk of the bias of the included RCTs according to the Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.1. The Cochrane Collaboration＇s software RevMan 5.0 was used for meta-analysis. Results Thirty-nine RCTs were enrolled in the review, including 2 351 patients with type 2 diabetic kidney disease met the inclusion criteria. Most of these trials were small and of low quality with a high risk of bias. The results of meta-analysis showed that ① Sodium ferulate was better on attenuating UAER （WMD=-42.92, 95%CI -52.61 to -33.23）, 24 hours urinary protein （WMD=-0.11, 95%CI -0.16 to -0.05）, BUN （WMD=-0.76, 95%CI -1.04 to -0.46） and Scr （WMD=-8.38, 95%CI -11.81 to -4.94）; Sodium ferulate was better on the regulation of FBG and 2 h-BG of clinical DKD （WMD= -2.39, 95%CI -3.23 to -1.54）, but not superior to routine treatment on the improvement of HbAlc （WMD=-0.12, 95%CI -0.27 to 0.02） and 2 h-BG of early DKD （WMD=-0.22, 95%CI -0.49 to 0.04）; Sodium ferulate was better on the improvement of SBP and MAP, however, Sodium ferulate was not superior to routine treatment on the improvement of DBP; Sodium ferulate was better on the improvement of TC （WMD=-0.70, 95%CI -1.01 to -0.39）, HDL-c （WMD= 0.14, 95%CI 0.06 to 0.22） and TG of clinical DKD （WMD=-0.96, 95%CI -1.49 to -0.43）, but not superior to routine treatment on the improvement of TG of early DKD （WMD=-0.12, 95%CI -0.28 to 0.04）; Sodium ferulate was better on the improvement of serum endothelin （WMD=-18.72, 95%CI -25.20 to -12.23） and urinary endothelin （WMD=-8.55, 95%CI -10.92 to -6.18）. Only 8 studies mentioned sodium ferulate during treatment no adverse reactions or side effects, reportedly found in a study of mild and transient headache and a study of fatigue and dizziness. We have not seen the serious adverse events. Conclusions Current evidence demonstrates that Sodium ferulate has certain effect and relatively safe in treating patients with diabetic kidney disease.Due to the heterogeneity and the high risk of bias in included studies,the evidence is insufficient to determine the effect of sodium ferulate.Further large-scale trials are required to define the role of sodium ferulate in the treatment of DKD.