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尿液生物标志物 [组织金属蛋白酶抑制因子-2(TIMP-2)] × [胰岛素样生长因子结合蛋白7(IGFBP7)] 在急性肾损伤风险评估中的临床应用

Clinical Use of the Urine Biomarker [TIMP-2] × [IGFBP7] for Acute Kidney Injury Risk Assessment.

作者信息

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

机构信息

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.

出版信息

Am J Kidney Dis. 2016 Jul;68(1):19-28. doi: 10.1053/j.ajkd.2015.12.033. Epub 2016 Mar 4.

DOI:10.1053/j.ajkd.2015.12.033
PMID:26948834
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4921267/
Abstract

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.

摘要

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。

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本文引用的文献

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Effect of remote ischemic preconditioning on kidney injury among high-risk patients undergoing cardiac surgery: a randomized clinical trial.远程缺血预处理对高危心脏手术患者肾损伤的影响:一项随机临床试验。
JAMA. 2015 Jun 2;313(21):2133-41. doi: 10.1001/jama.2015.4189.
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The urine sediment as a biomarker of kidney disease.尿沉渣作为肾脏疾病的生物标志物。
Am J Kidney Dis. 2015 Nov;66(5):748-55. doi: 10.1053/j.ajkd.2015.02.342. Epub 2015 May 2.
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Urinary biomarkers TIMP-2 and IGFBP7 early predict acute kidney injury after major surgery.
心脏手术后相关急性肾损伤的生物标志物:缩小范围
JTCVS Open. 2025 Apr 15;25:264-274. doi: 10.1016/j.xjon.2025.03.021. eCollection 2025 Jun.
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Impact of gender differences on optimal oxygen delivery thresholds to prevent acute kidney injury in cardiac surgeries with cardiopulmonary bypass.性别差异对体外循环心脏手术中预防急性肾损伤的最佳氧输送阈值的影响。
JTCVS Open. 2025 Jan 20;24:271-279. doi: 10.1016/j.xjon.2025.01.001. eCollection 2025 Apr.
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Biomarkers in Contrast-Induced Nephropathy: Advances in Early Detection, Risk Assessment, and Prevention Strategies.造影剂肾病中的生物标志物:早期检测、风险评估及预防策略的进展
Int J Mol Sci. 2025 Mar 21;26(7):2869. doi: 10.3390/ijms26072869.
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The role of IGFBP-1 in the clinical prognosis and pathophysiology of acute kidney injury.胰岛素样生长因子结合蛋白-1在急性肾损伤临床预后及病理生理学中的作用
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Lancet. 2015 May 16;385(9981):1966-74. doi: 10.1016/S0140-6736(15)60266-5. Epub 2015 Feb 26.
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Furosemide Stress Test and Biomarkers for the Prediction of AKI Severity.速尿应激试验及生物标志物对急性肾损伤严重程度的预测作用
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