Recent Successes in the Identification, Development, and Qualification of Translational Biomarkers: The Next Generation of Kidney Injury Biomarkers
Recent Successes in the Identification, Development, and Qualification of Translational Biomarkers: The Next Generation of Kidney Injury Biomarkers
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DOI：
10.1177/0192623314554840
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发表时间：
2015-01-01
影响因子：
1.5
通讯作者：
Adler, Scott
中科院分区：
文献类型：
--
作者：
Ennulat, Daniela;Adler, Scott
新型安全性或有效性生物标志物的开发越来越多地用于改善安全性监测并最大限度地减少药物开发过程中的损耗；然而，对于新的生物标志物，失败率可能等于或超过新化学实体的失败率。药物引起的肾损伤被认为发生在整个药物开发过程中，组织病理学被认为是临床前毒理学筛查的金标准。临床上使用的肾脏生物标志物主要是肾功能的生物标志物，在首次人体研究中被认为对检测药物引起的肾损伤不敏感，特别是对于已知在临床前物种中诱导肾损伤的化合物。最近公私合作伙伴关系的努力在大鼠肾损伤的几种新的可翻译生物标志物的鉴定、开发和鉴定方面取得了前所未有的成功。为了优化当前和未来临床前物种和人类生物标志物工作的成功机会，生物标志物的选择和开发应强调生物学考虑因素，包括标志物变异性以及健康和疾病中的生物学。目前正在进行支持新型肾脏安全标志物在临床环境中常规使用的鉴定的研究，并且非常期待这项工作的结果。
The development of novel safety or efficacy biomarkers has increasingly been used to improve safety monitoring and minimize attrition during drug development; however, for new biomarkers, the failure rate can equal or exceed that of new chemical entities. Drug-induced kidney injury is recognized to occur throughout the drug development process, with histopathology considered to be the gold standard for preclinical toxicologic screening. Renal biomarkers used clinically are primarily biomarkers of renal function and are considered insensitive for the detection of drug-induced kidney injury during first-in-man studies, particularly for compounds known to induce renal injury in preclinical species. Recent efforts by public-private partnerships have led to unprecedented success in the identification, development, and qualification of several new translatable biomarkers of kidney injury in the rat. To optimize the chance of success in current and future biomarker efforts in preclinical species and man, selection and development of biomarkers should emphasize biological considerations including marker variability and biology in both health and disease. The research to support the qualification of novel renal safety markers for routine use in the clinical setting is currently underway, and results from this work are greatly anticipated.