Diagnostic and Prognostic Relevance of Acute Kidney Injury Biomarkers in the ICU

ICU 急性肾损伤生物标志物的诊断和预后相关性

• 批准号: 8190130
• 负责人: Edward D Siew
• 金额: $ 17.28万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8190130
• 关键词: Acute; Acute Lung Injury; Acute Renal Failure with Renal Papillary Necrosis; Adoption; Adult; Adult Respiratory Distress Syndrome; American; Award; Biological Markers; Biological Markers; Biometry; Cardiac; Cardiopulmonary Bypass; Caring; Cessation of life; Clinical; Clinical Research; Clinical Trials; Comorbidity; Complex; Coupling; Creatinine; Critical Illness; Data; Data Collection; Detection; Development; Diagnosis; Diagnostic; Dialysis procedure; Disease; Early Diagnosis; Early identification; Enrollment; Epidemiology; Funding; Future; Goals; Incidence; Inflammation; Injury; International; Intervention; Ischemia; K-Series Research Career Programs; Kidney; Learning; Length of Stay; Liquid Chromatography; Mentored Patient-Oriented Research Career Development Award; Mentorship; Morbidity - disease rate; National Heart, Lung, and Blood Institute; Nephrology; Outcome; Output; Pathogenesis; Patient Care; Patients; Phenotype; Population; Predictive Value; Process; Proteins; Proteomics; Relative (related person); Research; Research Personnel; Research Priority; Risk; Role; Series; Serum; Shotguns; Societies; Specific qualifier value; Standardization; Stratification; Symptoms; Techniques; Technology; Testing; Time; Translating; Troponin; Tubular formation; Urine; Validation; base; candidate marker; case control; cohort; design; experience; glomerular filtration; high risk; improved; indexing; insight; investigator training; mortality; novel; outcome forecast; patient population; pre-clinical; prognostic; programs; prospective; skills; tandem mass spectrometry; translational study

DESCRIPTION (provided by applicant): The Mentored Patient-Oriented Research Career Development Award (K23) will enable Dr. Edward D. Siew to develop into an independent investigator in the clinical and translational study of acute kidney injury (AKI) and establish an independent research program focused on critical illness-associated kidney injury. Through the availability of a carefully constructed program of didactic activities in clinical proteomics, advanced epidemiology, and biostatistics; intensive mentorship by local and international experts; and direct experience in the design, implementation, and interpretation of data derived from a large prospective cohort of critically ill adults, Dr. Siew will use this award to become a highly trained investigator in AKI research. The primary scientific aims of this proposal are to examine the independent and additive impact of biological markers of injury for the early detection and prognosis of AKI in the critically ill and to apply emerging proteomic technology towards the discovery of novel protein markers able to predict progression of injury at the time of early diagnosis. Despite advances in the provision of care, AKI remains a common and devastating occurrence in the critically ill and an independent predictor of morbidity and mortality. Attempts at translating promising interventions into improved outcomes in AKI have been limited belated and unreliable markers of injury (i.e. changes in serum creatinine and urine output) that provide little information on the timing and mechanisms of ongoing injury. These limitations are further magnified in a mixed ICU patient population where the timing and extent of injury is more difficult to define. Using a large, well- phenotyped prospective cohort of critically ill adults (The Validation of Biomarkers for Acute Lung Injury Diagnosis/VALID Study), this proposal will test the hypothesis that a biomarker panel consisting of specific indicators of kidney injury will have independent and additive value for the early diagnosis and prognosis of AKI in a mixed adult ICU population (Specific Aims 1a and 1b). The candidate will learn to apply emerging proteomic techniques such as liquid- chromatography tandem mass-spectrometry (LC-MS-MS) towards discovering and verifying new potential protein targets able to predict progression of injury at the time of initial AKI diagnosis (Specific Aim 2). The proposed research plan will further define the role of promising candidate markers in providing additional pathophysiologic insight, enhancing risk stratification, and facilitating clinical trial enrollment. Further, the research included in this proposal will also provide this candidate with the skill set and experience to develop into a successful independent investigator able to make significant contributions toward improving the care of patients with this disease. PUBLIC HEALTH RELEVANCE: Progress towards improving outcomes in acute kidney injury (AKI) in the critically ill has been limited by the use of belated and unreliable markers of injury (i.e. serum creatinine, urine output). The proposed career development award application seeks to leverage the strengths of a large well-characterized cohort of 2550 critically ill adult patients (VALID - HL081332). The overarching aims are to validate candidate biological markers of injury able to improve the accuracy and timeliness of AKI diagnosis and prognosis as well as to apply emerging proteomic technology towards identifying patients at risk for progressive injury.

描述（由申请人提供）：以患者为导向的研究职业发展奖（K23）将使 Edward D. Siew 博士能够发展成为急性肾损伤（AKI）临床和转化研究的独立研究者，并建立独立的研究机构研究计划的重点是危重疾病相关的肾损伤。通过精心构建的临床蛋白质组学、高级流行病学和生物统计学教学活动计划；当地和国际专家的深入指导； Siew 博士在设计、实施和解释来自大量危重成人前瞻性队列的数据方面拥有直接经验，他将利用这一奖项成为 AKI 研究领域训练有素的研究者。该提案的主要科学目的是检查损伤生物标志物对危重患者 AKI 早期检测和预后的独立和附加影响，并应用新兴的蛋白质组学技术来发现能够预测 AKI 进展的新型蛋白质标志物。早期诊断时受伤。尽管在提供护理方面取得了进步，但 AKI 仍然是危重病患者中常见且具有破坏性的事件，并且是发病率和死亡率的独立预测因素。将有希望的干预措施转化为改善 AKI 结局的尝试受到了迟来且不可靠的损伤标志物（即血清肌酐和尿量的变化）的限制，这些标志物提供的关于持续损伤的时间和机制的信息很少。这些限制在混合 ICU 患者群体中进一步放大，因为损伤的时间和程度更难以确定。该提案将使用大量表型良好的危重成人前瞻性队列（急性肺损伤诊断生物标志物验证/有效研究）来检验以下假设：由特定肾损伤指标组成的生物标志物组将具有独立和相加的作用。对于混合成人 ICU 人群中 AKI 的早期诊断和预后的价值（具体目标 1a 和 1b）。候选人将学习应用新兴的蛋白质组学技术，例如液相色谱串联质谱 (LC-MS-MS) 来发现和验证能够在初始 AKI 诊断时预测损伤进展的新的潜在蛋白质靶点（具体目标 2） ）。拟议的研究计划将进一步明确有前途的候选标志物在提供额外的病理生理学见解、增强风险分层和促进临床试验注册方面的作用。此外，该提案中包含的研究还将为该候选人提供技能和经验，使其成为一名成功的独立研究者，能够为改善这种疾病患者的护理做出重大贡献。 公共卫生相关性：由于使用迟来且不可靠的损伤标志物（即血清肌酐、尿量），改善危重病人急性肾损伤（AKI）结局的进展受到限制。拟议的职业发展奖申请旨在利用 2550 名危重成年患者的大型特征队列的优势（VALID - HL081332）。总体目标是验证候选的损伤生物标志物，能够提高 AKI 诊断和预后的准确性和及时性，并应用新兴的蛋白质组学技术来识别有进行性损伤风险的患者。