双膦酸盐类药物致肾毒性的Meta-分析

目的 采用系统评价的方法研究双膦酸盐对患者肾毒性发生率、肌酐和尿素氮的影响。方法 计算机检索Pubmed，Embase，Cochrane Library，中国学术期刊全文数据库（CNKI）、中国生物医学文献数据库（CBM）、维普数据库（VIP）和万方数据库，从建库起到2018年1月25日，限定语言为英语和汉语的随机对照试验（RCT）和前瞻性非随机对照试验。筛选文献，提取数据，运用Stata 12.0进行系统评价。结果 最终纳入8个RCTs和8个前瞻性非随机对照临床试验，共11 240名患者。Meta-分析结果显示：与对照组相比，双膦酸盐显著增加患者发生肾毒性的风险[OR=1.58，95%CI（1.28，1.95），P<0.000 1]；而双膦酸盐治疗组与对照组比较，在血清肌酐和尿素氮方面，无显著性差异[MD=-1.06，95%CI（-5.43，3.30），P=0.63；MD=-0.07，95%CI（-0.32，0.19），P=0.61]。通过对患者使用的双膦酸盐种类、患者基础疾病、患者的平均年龄、不同试验类型以及给药途径进行亚组分析，双膦酸盐组肌酐值与对照组亦无统计学差异。结论 双膦酸盐明显增加了患者发生肾毒性的风险，但血清肌酐和尿素氮两种肾脏指标并无显著性差异。建议在今后双膦酸盐的应用中纳入更多肾毒性相关指标，以帮助临床更早的发现患者的肾损害。

Nephrotoxicity of bisphosphonate: a Meta-analysis

Objective The influences of bisphosphonates on the incidence rate of nephrotoxicity,creatinine (Cr) and blood urea nitrogen (BUN) of patients were studied by system evaluation method.Methods Randomized controlled trials (RCTs) and prospective non randomized controlled trials which were published in English or Chinese were systematically retrieved by computer in the Pubmed,Embase,Cochrane Library,China National Knowledge Infrastructure (CNKI),China Biology Medicine disc (CBM),VIP and Wanfang Datebase from the establishment of the datebase to January 25,2018.The literatures were screened and data were extracted,the system evaluation was performed by Stata 12.0.Results A total of 8 RCTs and 8 prospective non randomized controlled trials involving 11 240 patients were finally included in this study.The Meta-analysis results showed that bisphosphonates significantly increased the risk of nephrotoxicity of patients in comparison with control groups[OR=1.58,95%CI(1.28,1.95),P<0.000 1].However,there was no significant difference of Cr and BUN between bisphosphonates and control groups[MD=-1.06,95%CI(-5.43,3.30),P=0.63;MD=-0.07,95%CI(-0.32,0.19),P=0.61].According to the subgroup analysis of types of bisphosphonates,underlying diseases,average age of the patients,different types of trials and administration route,there were no statistical differences of creatinine value between bisphosphonates and control groups.Conclusion Bisphosphonates significantly increased the risk of nephrotoxicity,but there were no significant differences in Cr and BUN.It is suggested that more indicators of nephrotoxicity should be included in the future application of bisphosphonate to help early detection of renal damage of patients.