Prognostic markers in postoperative acute kidney injury

描述（由申请人提供）：心脏手术后急性肾损伤（AKI）与死亡率增加20倍相关。在需要透析的患者中，死亡风险增加了70倍。肾损伤的程度是可变的，难以预测。肾损伤的危险因素已经被描述过，但它们并不能预测一个病人是否会发展成肾衰竭。目前还没有准确的生物标志物来预测肾损伤患者的预后。缺乏预测性生物标志物是研究AKI新疗法的一个障碍。预后标志物可以确定哪些患者应该进行新疗法的试验。在确定诊断和早期生物标志物方面正在作出重大努力。然而，在识别预测AKI中疾病程度和病程的标志物方面，进展甚微。该项目的目的是确定心脏手术后AKI预后的生物标志物。我们已经建立了一个AKI专家小组，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关系，他们之前已经确定了生物标志物。将在四个中心收集心脏手术后发生AKI的患者的尿液。主要结局变量是对肾脏替代治疗的需求。我们将预测临床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。标记是根据已发表的文献和我们自己的初步数据选择的。它们包括小管损伤、炎症反应、小管功能、功能恢复和透析进展的候选标记物。在第二个目标中，我们将使用两种蛋白质组学技术，2D电泳与DIGE和MALDI多肽分析来识别新的标记。这些发现研究的目标是找到新的标记物，可以与目标1中的最佳标记物结合使用。我们通过这两种技术提供了初步数据，其中我们已经确定了生物标志物。在第三个目标中，我们将选择候选标记物，在使用独立于前两个目标中使用的第二组患者的最终分析中进行组合。最后，我们将在由590名新患者组成的第三组中验证用于识别它们的标记和算法。这些研究将结合假设驱动和基于发现的方法来寻找生物标志物的最佳组合，以预测急性肾损伤的过程。

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.