...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Critical care : >Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury
【24h】

Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury

机译：在人类急性肾损伤中细胞周期阻滞生物标志物的发现和验证

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

IntroductionAcute kidney injury (AKI) can evolve quickly and clinical measures of function often fail to detect AKI at a time when interventions are likely to provide benefit. Identifying early markers of kidney damage has been difficult due to the complex nature of human AKI, in which multiple etiologies exist. The objective of this study was to identify and validate novel biomarkers of AKI.MethodsWe performed two multicenter observational studies in critically ill patients at risk for AKI - discovery and validation. The top two markers from discovery were validated in a second study (Sapphire) and compared to a number of previously described biomarkers. In the discovery phase, we enrolled 522 adults in three distinct cohorts including patients with sepsis, shock, major surgery, and trauma and examined over 300 markers. In the Sapphire validation study, we enrolled 744 adult subjects with critical illness and without evidence of AKI at enrollment; the final analysis cohort was a heterogeneous sample of 728 critically ill patients. The primary endpoint was moderate to severe AKI (KDIGO stage 2 to 3) within 12 hours of sample collection.ResultsModerate to severe AKI occurred in 14% of Sapphire subjects. The two top biomarkers from discovery were validated. Urine insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in AKI, together demonstrated an AUC of 0.80 (0.76 and 0.79 alone). Urine [TIMP-2]·[IGFBP7] was significantly superior to all previously described markers of AKI (P 0.72. Furthermore, [TIMP-2]·[IGFBP7] significantly improved risk stratification when added to a nine-variable clinical model when analyzed using Cox proportional hazards model, generalized estimating equation, integrated discrimination improvement or net reclassification improvement. Finally, in sensitivity analyses [TIMP-2]·[IGFBP7] remained significant and superior to all other markers regardless of changes in reference creatinine method.ConclusionsTwo novel markers for AKI have been identified and validated in independent multicenter cohorts. Both markers are superior to existing markers, provide additional information over clinical variables and add mechanistic insight into AKI.Trial registrationClinicalTrials.gov number NCT01209169.
机译：简介急性肾脏损伤（AKI）可以迅速发展，并且在可能提供干预措施的时候，临床功能指标通常无法检测到AKI。由于人类AKI的复杂性质（存在多种病因），很难确定肾脏损害的早期标记。这项研究的目的是鉴定和验证AKI的新型生物标志物。方法我们对处于AKI风险中的重症患者进行了两项多中心观察性研究-发现和验证。来自发现的前两个标记在第二项研究（蓝宝石）中得到了验证，并与许多先前描述的生物标记进行了比较。在发现阶段，我们在三个不同的队列中招募了522名成年人，包括败血症，休克，大手术和创伤患者，并检查了300多个标记。在Sapphire验证研究中，我们招募了744名成年危重病患者，但没有AKI证据。最终的分析队列是728名重症患者的异质性样本。主要终点为样本采集后12小时内的中度至重度AKI（KDIGO第2至3期）。结果在14％的蓝宝石受试者中发生了中度至重度AKI。来自发现的两个顶级生物标志物得到了验证。尿样胰岛素样生长因子结合蛋白7（IGFBP7）和金属蛋白酶2组织抑制剂（TIMP-2），两者都是G1细胞周期阻滞的诱导物，这是AKI的关键机制，两者的AUC均为0.80（0.76和仅0.79）。尿液[TIMP-2]·[IGFBP7]显着优于所有先前描述的AKI标记（P 0.72。此外，当分析时，[TIMP-2]·[IGFBP7]添加到九变量临床模型中可显着改善风险分层最后，在敏感性分析中，无论参考肌酐方法的变化如何，[TIMP-2]·[IGFBP7]仍显着优于其他所有标记。已经在独立的多中心队列中鉴定并验证了AKI的标记，这两种标记均优于现有标记，可提供有关临床变量的更多信息，并为AKI提供更多的机械原理。试验注册临床试验.gov编号NCT01209169。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号