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Comparative Evaluation of Urinary Biological Markers for the Prognostic Stratific

尿液生物标志物预后分层的比较评估

基本信息

批准号：
7585716
负责人：
BERTRAND L JABER
金额：
$ 6.33万
依托单位：
STEWARD ST. ELIZABETH'S MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-04-01 至 2011-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7585716
关键词：
APACHE II Acute Kidney Failure Acute Physiology and Chronic Health Evaluation Acute Renal Failure with Renal Papillary Necrosis Adult American Authorization documentation Award Benign Biological Biological Markers Biological Markers Brush Border Cessation of life Characteristics Clinical Cohort Studies Collection Communities Comparative Study Complication Consultations Creatinine Critical Illness Critical Pathways Databases Dependency Development Dialysis procedure Disease Early Diagnosis Enrollment Enzymes Etiology Evaluation Extracellular Fluid Foundations Gelatinase A Glucosaminidase Goals Grant Hospital Mortality Hospitals Incidence Individual Injury Intensive Care Units Interleukin-18 Kidney Knowledge Laboratories Letters Measures Mediator of activation protein Medical National Institute of Diabetes and Digestive and Kidney Diseases Nephrology Observational Study Outcome Outcomes Research Output Patients Performance Physiological Process Proliferation Marker Proteins Proteomics Recovery Renal Replacement Therapy Renal function Reporting Research Research Personnel Research Project Grants Research Subjects Risk Sampling Series Serum Severities Severity of illness Societies Standardization Stratification Supportive care Surrogate Markers Syndrome Testing Therapeutic Intervention Time Tubular formation United States Food and Drug Administration Urine Validation Waste Products absorption base clinical practice clinically relevant cohort comparative design enzyme activity improved insight member mortality novel post gamma-globulins product development prognostic prognostic indicator prospective rat KIM-1 protein repository tool treatment strategy urinary

项目摘要

DESCRIPTION (provided by applicant): Acute renal failure (ARF) is a serious complication in hospitalized patients and is frequently associated with adverse clinical outcomes. However, ARF can also be associated with a more benign, self-limited clinical course. Patients at risk for adverse outcomes are often not easily distinguished from those with a more benign course, making the appropriate and timely application of treatment strategies a difficult task. Novel, prognostic tools that can improve risk stratification among patients with ARF are therefore urgently needed. In recent years, an increasing number of urinary biological markers of acute kidney injury have been described. Among these, the most clinically relevant urinary markers include Kidney Injury Molecule-1 (KIM-1) (a tubular dedifferentiation marker), Neutrophil Gelatinase-Associated Lipocalin (NGAL) (a tubular proliferation marker), interleukin-18 (IL-18) (a mediator of tubular ischemic injury), N-acetyl-(-D-glucosaminidase (NAG) (a tubular brush border enzyme), cystatin C and (-1 microglobulin (two markers of impaired tubular protein absorption). Although predominantly studied for the early detection of ARF, some of these markers might also predict adverse clinical outcomes among patients with established ARF, and therefore, might be useful for risk stratification. To date, no studies have evaluated the performance characteristics of the above-mentioned urinary biological markers for the prediction of adverse outcomes in patients with established ARF in a comprehensive and comparative fashion. The hypotheses to be investigated are that urinary KIM-1, NGAL, IL-18, NAG, cystatin C, and (-1 microglobulin, individually or in combination, are superior to clinical prognostic scores in predicting adverse outcomes in patients with established ARF, including dialysis requirement and hospital mortality. We will test these hypotheses in a large cohort of 300 hospitalized patients with ARF, of which over 200 have already been accrued. We will also combine urinary biological markers with or without the addition of a clinical prognostic score, and compare the performance characteristics of these combinations with that of single prognostic tests. We expect to demonstrate that individual markers are associated with adverse outcomes in patients with established ARF, and might be superior to clinical prognostic scores. We further hypothesize that a combination of two or more markers will increase prognostic accuracy for predicting adverse outcomes. The research project is achievable as two thirds of the cohort has already been enrolled, and offers important new insights into the prognostic value of urinary biomarkers for the prediction of adverse outcomes in patients with ARF. This study might provide a foundation for the development of a more reliable prognostic risk stratification tool in ARF, which will be validated externally in other ARF cohorts, and help provide a more guided therapeutic intervention for patients with ARF.

描述(由申请人提供)：急性肾功能衰竭(ARF)是住院患者的严重并发症，常与不良临床结局相关。然而，ARF也可以与更良性的、自我限制的临床病程相关。有不良后果风险的患者往往不容易与病程较良性的患者区分开来，这使得适当和及时地应用治疗策略成为一项艰巨的任务。因此，迫切需要能够改善ARF患者风险分层的新的预后工具。近年来，越来越多的尿液生物标志物被描述为急性肾损伤。其中，临床上最相关的尿液标志物包括肾损伤分子-1(Kim-1)(一种肾小管去分化标志物)、中性粒细胞明胶酶相关脂蛋白(NGAL)(一种肾小管增殖标志物)、白细胞介素18(IL-18)(一种肾小管缺血性损伤的介质)、N-乙酰-(-D-氨基葡萄糖苷酶)(一种肾小管刷状边缘酶)、胱抑素C和(-1)微球蛋白(两种肾小管蛋白吸收受损的标志物)。虽然这些标记物主要用于ARF的早期检测，但其中一些标记物也可能预测已确诊的ARF患者的不良临床结果，因此，可能对风险分层有用。到目前为止，还没有研究以全面和比较的方式评估上述尿生物标志物在预测已确诊ARF患者不良结局方面的表现特征。要研究的假设是，尿Kim-1、NGAL、IL-18、NAG、半胱氨酸氨基转移酶C和(-1)微球蛋白单独或结合在一起，在预测已确诊的ARF患者的不良结果(包括透析需求和住院死亡率)方面优于临床预后评分。我们将在300名ARF住院患者中检验这些假设，其中200多人已经累积。我们还将结合尿液生物标志物和临床预后评分，并将这些组合的表现特征与单一预后测试进行比较。我们期望证明个体标记物与已确诊的急性肾衰患者的不良结局相关，并且可能优于临床预后评分。我们进一步假设，两个或两个以上标记物的组合将增加预测不良结果的预后准确性。这项研究项目是可以实现的，因为三分之二的队列已经入选，并为预测ARF患者不良结局的尿液生物标记物的预后价值提供了重要的新见解。这项研究可能为开发一种更可靠的ARF预后风险分层工具提供基础，该工具将在其他ARF队列中得到外部验证，并有助于为ARF患者提供更具指导性的治疗干预。