肾毒性生物标志物临床前研究及应用进展  

Progress in preclinical research and application of nephrotoxic biomarkers

作　　者：朱聪[1,2] 黄芝瑛[2] 周晓冰[1] 李波[1] 

机构地区：[1]中国食品药品检定研究院国家药物安全评价监测中心 药物非临床安全评价研究北京市重点实验室,北京100176 [2]中山大学药学院药物安全性评价中心,广州510006

出　　处：《中国新药杂志》2014年第4期391-396,共6页Chinese Journal of New Drugs

基　　金：国家“重大新药创制”科技重大专项(2012ZX09302001);中国食品药品检定研究院中青年发展研究基金(2011C3)

摘　　要：肾脏是药物毒性的重要靶器官之一。目前两个重要的肾毒性生物标志物BUN和CRE缺乏特异性和灵敏度,鉴于此,已有8个新的肾毒性生物标志物被FDA和EMA认可用于药物临床前安全性评价。另外,一些易于检测的尿酶可以联合运用预测肾毒性,新的蛋白和核酸类生物标志物不断被发现,其中microRNA成为研究热点。已被认可的8个生物标志物有的被用于预测肾小球损伤,有的被用于预测肾小管损伤,联合运用生物标志物将更好地预测药物肾毒性和诊断肾脏疾病。对于不同机制和程度的肾毒性,血清或尿液中的生物标志物变化水平不同,尚需要更多的探索和验证工作。Kidney is the major nephrotoxicity-blood urine nitrogen and target of drug-induced nephrotoxicity. The two most important biomarkers of serum creatinine are lack of specificity and sensitivity. In view of this, eight new biomarkers of nephrotoxicity have been qualified by FDA and EMEA for preclinical drug safety assessment. In addition, some enzymuria that are easy to detect can be used in combination to predict renal damage; and some proteins and nucleic acids are newly discovered as biomarkers of nephrotoxicity, of them, microRNAs become a re- search hotspot. Of eight qualified biomarkers, some of them are used to predict proximal tubular damage, and others are used to predict glomerular damage. Combined use of them will facilitate drug safety evaluation and renal damage diagnosing. The changes in serum or urine biomarkers vary from different mechanisms and degrees of nephrotoxicity, so more exploration and verification studies are needed.

关 键 词：肾毒性 生物标志物 应用进展 

分 类 号：R991[医药卫生—毒理学]