Vijayan Anitha, Faubel Sarah, Askenazi David J, Cerda Jorge, Fissell William H, Heung Michael, Humphreys Benjamin D, Koyner Jay L, Liu Kathleen D, Mour Girish, Nolin Thomas D, Bihorac Azra
Renal Division, Department of Medicine, Washington University in St. Louis, St. Louis, MO.
Renal Division, University of Colorado Denver and Denver VA Medical Center, Denver, CO.
Am J Kidney Dis. 2016 Jul;68(1):19-28. doi: 10.1053/j.ajkd.2015.12.033. Epub 2016 Mar 4.
Acute kidney injury (AKI) is a serious complication, commonly occurring in the critically ill population, with devastating short- and long-term consequences. Despite standardization of the definition and staging of AKI, early recognition remains challenging given that serum creatinine level is a marker, albeit imperfect, of kidney function and not kidney injury. Furthermore, the delay in increase in serum creatinine level after loss of glomerular filtration also prevents timely detection of decreased kidney function in patients with AKI. During the past decade, numerous clinical investigations have evaluated the utility of several biomarkers in the early diagnosis and risk stratification of AKI. In 2014, the US Food and Drug Administration approved the marketing of a test based on the combination of urine concentrations of tissue inhibitor of metalloproteinase 2 and insulin-like growth factor binding protein 7 ([TIMP-2] × [IGFBP7]) to determine whether certain critically ill patients are at risk for developing moderate to severe AKI. The optimal role of this biomarker in the diagnosis, management, and prognosis of AKI in different clinical settings requires further clarification. In this perspective, we summarize the biological actions of these 2 cell-cycle arrest biomarkers and present important considerations regarding the clinical application, interpretation, and limitations of this novel test for the early detection of AKI.
急性肾损伤(AKI)是一种严重并发症,常见于危重症人群,会产生严重的短期和长期后果。尽管AKI的定义和分期已实现标准化,但鉴于血清肌酐水平虽是肾功能的一个指标(尽管并不完美)而非肾损伤指标,早期识别仍具有挑战性。此外,肾小球滤过功能丧失后血清肌酐水平升高的延迟也阻碍了对AKI患者肾功能下降的及时检测。在过去十年中,众多临床研究评估了几种生物标志物在AKI早期诊断和风险分层中的效用。2014年,美国食品药品监督管理局批准了一项基于金属蛋白酶组织抑制因子2和胰岛素样生长因子结合蛋白7尿液浓度组合([TIMP-2]×[IGFBP7])的检测方法上市,以确定某些危重症患者是否有发生中度至重度AKI的风险。这种生物标志物在不同临床环境中对AKI的诊断、管理及预后的最佳作用尚需进一步明确。在此观点中,我们总结了这两种细胞周期阻滞生物标志物的生物学作用,并针对这种用于早期检测AKI的新型检测方法的临床应用、解读及局限性提出重要考量。