Prognostic markers in postoperative acute kidney injury

术后急性肾损伤的预后标志物

• 批准号: 8100426
• 负责人: JOHN M. ARTHUR
• 金额: $ 35.89万
• 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 2012-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8100426
• 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; 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（阿基）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。肾损伤的风险因素已经被描述，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阿基新疗法研究的障碍。预后标志物可以确定应进行新疗法测试的患者亚组。目前正在努力确定诊断和早期生物标志物。然而，在确定预测阿基疾病程度和病程的标志物方面几乎没有取得进展。该项目的目标是确定心脏手术后阿基预后的生物标志物。我们已经建立了一个阿基专家团队，将在四个研究中心收集患者样本。蛋白质组学、统计学和信息学合作者已经建立了相互合作，其中他们先前已经确定了生物标志物。将在四个中心采集心脏手术后发生阿基的患者的尿液。主要结局变量是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。标记物的选择基于已发表的文献和我们自己的初步数据。它们包括肾小管损伤、炎症反应、肾小管功能、功能恢复和透析进展的候选标志物。在第二个目标中，我们将使用两种蛋白质组学技术，二维电泳与DIGE和MALDI多肽分析，以确定新的标记。这些发现研究的目标是找到新的标记，可以与目标1中的最佳标记组合使用。我们提供了两种技术的初步数据，其中我们已经确定了生物标志物。在第三个目标中，我们将选择候选标志物，以使用第二组患者进行最终测定，该第二组患者独立于前两个目标中使用的组。最后，我们将在由590名新患者组成的第三组中验证标记物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，以找到预测急性肾损伤过程的生物标志物的最佳组合。

项目成果

Urinary sediment cast scoring index for acute kidney injury: a pilot study.

• DOI: 10.1159/000166605
• 发表时间: 2008
• 期刊: NEPHRON CLINICAL PRACTICE
• 作者: Chawla, Lakhmir S.;Dommu, Aaron;Berger, Alexandra;Shih, Shirley;Patel, Samir S.
• 通讯作者: Patel, Samir S.

Identification of Diagnostic Urinary Biomarkers for Acute Kidney Injury

急性肾损伤诊断性尿液生物标志物的鉴定

• DOI: 10.2310/jim.0b013e3181d473e7
• 发表时间: 2010
• 期刊: Journal of Investigative Medicine
• 影响因子: 2.6
• 作者: S. Varghese;T. B. Powell;M. Janech;M. Budisavljevic;R. Stanislaus;Jonas S. Almeida;J. Arthur
• 通讯作者: J. Arthur

Advanced diabetic nephropathy with nephrotic range proteinuria: a pilot study of the long-term efficacy of subcutaneous ACTH gel on proteinuria, progression of CKD, and urinary levels of VEGF and MCP-1.

伴有肾病范围蛋白尿的晚期糖尿病肾病：皮下 ACTH 凝胶对蛋白尿、CKD 进展以及尿 VEGF 和 MCP-1 水平的长期疗效的初步研究。

• DOI: 10.1155/2013/489869
• 发表时间: 2013
• 期刊: Journal of diabetes research
• 影响因子: 4.3
• 作者: Tumlin,JA;Galphin,CM;Rovin,BH
• 通讯作者: Rovin,BH