Prognostic markers in postoperative acute kidney injury

术后急性肾损伤的预后标志物

• 批准号: 7874675
• 负责人: JOHN M. ARTHUR
• 金额: $ 37.36万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7874675
• 关键词: Acute Kidney Failure; Acute Renal Failure with Renal Papillary Necrosis; Affect; Algorithms; Animal Model; Biological Assay; Biological Markers; Biological Markers; Brush Border; CCL2 gene; Cardiac Surgery procedures; Cell Death Process; Cessation of life; Clinical; Collaborations; Coronary Artery Bypass; Data; Development; Diagnostic; Dialysis procedure; Disease; Electrophoresis; Enzymes; Functional disorder; Glycoproteins; Goals; Human; Immune response; Incidence; Inflammatory; Inflammatory Response; Informatics; Injury; Intercellular adhesion molecule 1; Interleukin-18; Interleukin-6; Ischemia; Kidney; Kidney Failure; Knowledge; LIF gene; Length; Literature; Marker Discovery; Measurable; Measurement; Measures; Methodology; Methods; Natural regeneration; Nature; Nephrons; Operative Surgical Procedures; Outcome; Outcomes Research; Output; Patients; Pattern; Peptides; Plasma; Plasma Proteins; Postoperative Period; Process; Prognostic Marker; Protein Fragment; Proteins; Proteomics; Publishing; Recovery of Function; Renal Replacement Therapy; Retinol Binding Proteins; Risk; Risk Factors; Sampling; Severities; Site; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Surrogate Markers; Techniques; Testing; Time; Tubular formation; Two-Dimensional Gel Electrophoresis; UMOD gene; Urine; Zinc; alpha 1-Antitrypsin; alpha-1-microglobulin; base; candidate marker; cytokine; effective therapy; experience; high risk; improved; insight; mortality; novel marker; outcome forecast; polypeptide; primary outcome; prognostic; regenerative; response; response to injury; secondary outcome; urinary

DESCRIPTION (provided by applicant): Acute kidney injury (AKI) after cardiac surgery is associated with a 20 fold increase in mortality. Among patients who require dialysis, the risk of death is increased 70-fold. The magnitude of renal injury is variable and difficult to predict. Risk factors for kidney injury have been described but they do not predict if a given patient will develop renal failure. No accurate biomarkers currently exist to predict the prognosis of patients with kidney injury. The absence of predictive biomarkers is an impediment to studies of new therapies for AKI. Prognostic markers could identify the subset of patients in whom testing of new therapies should be performed. A significant effort is being made to identify diagnostic and early biomarkers. However, little progress has been achieved in identifying markers that predict the magnitude and course of the disease in AKI. The goal of this project is to identify biomarkers for prognosis in AKI after cardiac surgery. We have established a team of experts in AKI that will collect samples from patients at four sites. The proteomic, statistical and informatic collaborators have established collaborations with each other in which they have previously identified biomarkers. Urine will be collected from patients who develop AKI after cardiac surgery at four centers. The primary outcome variable is the requirement for renal replacement therapy. We will predict secondary outcomes that are either clinically useful or meaningful research outcomes. In the first aim we will measure candidate markers. The markers were chosen based on published literature and our own preliminary data. They include candidate markers for tubular injury, inflammatory response, tubular function, recovery of function, and progression to dialysis. In the second aim we will use two proteomic techniques, 2D electrophoresis with DIGE and MALDI polypeptide analysis to identify novel markers. The goal of these discovery studies is to find new markers that can be used in combination with the best markers from aim 1. We provide preliminary data with both techniques in which we have identified biomarkers. In the third aim we will select the candidate markers to be combined in a final assay using a second set of patients that is independent of the set used in the first two aims. Finally, we will validate the markers and the algorithm used to identify them in a third set consisting of 590 new patients. These studies will use a combination of hypothesis-driven and discovery based approaches to find the best combination of biomarkers to predict the course of acute kidney injury.

描述(由申请人提供)：心脏手术后的急性肾损伤(AKI)与死亡率增加20倍有关。在需要透析的患者中，死亡风险增加了70倍。肾脏损伤的程度是可变的，很难预测。肾损伤的危险因素已经被描述，但它们不能预测给定的患者是否会发展为肾功能衰竭。目前还没有准确的生物标志物来预测肾损伤患者的预后。缺乏可预测的生物标志物是AKI新疗法研究的障碍。预后标记物可以确定应该对哪些患者进行新疗法的测试。正在做出重大努力，以确定诊断和早期生物标记物。然而，在识别预测AKI病情严重程度和病程的标志物方面进展甚微。该项目的目标是确定心脏手术后急性心肌梗死患者预后的生物标志物。我们已经在AKI建立了一个专家团队，将在四个地点收集患者的样本。蛋白质组学、统计学和信息学的合作者已经建立了彼此之间的合作，在这些合作中，他们之前已经确定了生物标志物。尿液将从四个中心心脏手术后发生AKI的患者身上收集。主要的结果变量是对肾脏替代治疗的要求。我们将预测临床上有用或有意义的研究结果的次要结果。在第一个目标中，我们将测量候选标记。这些标记是根据已发表的文献和我们自己的初步数据选择的。它们包括肾小管损伤、炎症反应、肾小管功能、肾功能恢复和进展为透析的候选标志物。在第二个目标中，我们将使用两种蛋白质组学技术，即双向凝胶电泳和MALDI多肽分析来寻找新的标记。这些发现研究的目标是找到新的标记，可以与目标1中最好的标记结合使用。我们提供了这两种技术的初步数据，在这些技术中，我们已经识别了生物标记。在第三个目标中，我们将使用独立于前两个目标中使用的集合的第二组患者来选择要在最终分析中组合的候选标记物。最后，我们将在由590名新患者组成的第三组中验证标记和用于识别它们的算法。这些研究将使用假设驱动和基于发现的方法相结合的方法来寻找预测急性肾损伤过程的最佳生物标记物组合。