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：
7388341
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 2010-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7388341
关键词：
APACHE II Acute 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 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 Invasive Kidney Kidney Failure Knowledge Laboratories Letters Measures Mediator of activation protein Medical National Institute of Diabetes and Digestive and Kidney Diseases Nephrology Numbers Observational Study Outcome Output Patients Performance Personal Satisfaction Physical Dialysis Physiological Process Proliferation Marker Proteins Proteomics Rate Recovery Renal Replacement Therapy Renal function Reporting Research Research Personnel Research Project Grants Research Subjects Risk Sampling Score 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 clinically relevant cohort comparative design enzyme activity improved insight member mortality novel post gamma-globulins prognostic prospective rat KIM-1 protein repository tool 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）：急性肾衰竭（ARF）是住院患者的严重并发症，并且经常与不良临床结局有关。但是，ARF也可以与更良性，自限的临床过程相关联。通常不容易将处于不良结果的患者与患有更良性的病程的患者区分开，这使得对治疗策略的适当和及时应用成为艰巨的任务。因此，迫切需要新颖的预后工具可以改善ARF患者之间的风险分层。近年来，已经描述了越来越多的急性肾脏损伤的尿生物学标志物。 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）（一种管状刷边界酶），伴抑制蛋白C和（-1微球蛋白（肾小管蛋白吸收受损的两个标记）。尽管主要研究了ARF的早期检测，但其中一些标记物可能还可以预测固定ARF患者的不良临床外观，因此可能会导致风险分级。迄今为止，尚无研究评估上述尿液生物学标志物的性能特征，以预测以全面和比较的方式建立ARF患者的不良结果。待研究的假设是，尿尿Kim-1，ngal，IL-18，NAG，半胱氨酸蛋白酶C和（-1个单独或组合的-1微球蛋白，在预测临床预后不良后果中优于临床预后不良结局，包括这些疗程和医院的次数大量的均应均为3次，均为Arf。超过200个，我们还将在不增加临床预后评分的情况下结合尿液标记，并将这些组合的性能与单个预后测试的性能相比，我们希望单个标记与既定的ARF和更多的预后相关。预后的准确性可预测不良结果。该研究项目是可以实现的，因为已经招募了三分之二的队列，并且为尿生物标志物的预后价值提供了重要的新见解，以预测ARF患者的不良结果。这项研究可能为在ARF中开发更可靠的预后风险分层工具提供了基础，该工具将在其他ARF队列中进行外部验证，并有助于为ARF患者提供更具指导性的治疗干预措施。