Biomarker Effectiveness Analysis in Contrast Nephropathy (BEACON)

对比肾病的生物标志物有效性分析 (BEACON)

• 批准号: 9175298
• 负责人: Raghavan Murugan
• 金额: $ 26.42万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-20 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9175298
• 关键词: Acetylcysteine; Acute Renal Failure with Renal Papillary Necrosis; Address; Adverse event; Ancillary Study; Angiography; Area; Binding Proteins; Biological Markers; Blood Proteins; C-reactive protein; Cardiac; Cardiovascular system; Cell Cycle Arrest; Cessation of life; Characteristics; Chronic Kidney Failure; Clinical; Clinical Trials; Complication; Creatinine; Critical Illness; Dependence; Detection; Development; Diagnosis; Dialysis procedure; Dyes; Early Diagnosis; Effectiveness; Event; Functional disorder; Funding; Goals; Growth; Health; Health Policy; Healthcare; Heart failure; Hospitalization; Hour; Imaging Techniques; Injury; Insulin; Intravenous; Isotonic Exercise; Kidney; Kidney Diseases; Knowledge; Mission; Myocardial Infarction; National Institute of Diabetes and Digestive and Kidney Diseases; Natriuretic Peptides; Observational Study; Oral; Outcome; Output; Patient Monitoring; Patients; Physicians; Placebos; Plasma; Policy Maker; Predictive Value; Prevention; Prevention strategy; Primary Prevention; Procedures; Radiology Specialty; Randomized Clinical Trials; Renal Replacement Therapy; Research; Resources; Risk; Saline; Sampling; Secondary Prevention; Serum; Sodium Bicarbonate; Sodium Chloride; Specimen; Stratification; Stroke; Subgroup; Testing; Tissue Inhibitor of Metalloproteinases; Troponin I; United States Food and Drug Administration; Urine; Veterans; Work; abstracting; acute coronary syndrome; adverse outcome; base; biobank; biomarker panel; cardiovascular risk factor; clinical practice; compare effectiveness; early detection biomarkers; effective therapy; high risk; improved; interest; mortality; novel; predictive modeling; prevent; public health relevance; response; screening; urinary

ABSTRACT – THE BIOMARKER EFFECTIVENESS ANALYSIS IN CONTRAST NEPHROPATHY Contrast-induced acute kidney injury (CIAKI) is a serious complication occurring in patients with chronic kidney disease undergoing angiography and is associated with adverse renal and cardiovascular outcomes. We will address two key questions that remain in high-risk patients undergoing angiography. First, early detection of CIAKI after contrast exposure is problematic because rise in serum creatinine or decline in urine output occur over several days and many cases are under-diagnosed. Second, early risk stratification for long-term adverse events is also problematic because existing risk prediction models only have a modest predictive value. Availability of a biomarker that detects subclinical CIAKI before creatinine and also aids in risk stratification will change primary and secondary prevention strategies. The FDA has recently approved two novel, highly sensitive, urinary cell cycle arrest biomarkers for early detection of AKI. We have shown that these biomarkers: tissue inhibitor of metalloproteinase (TIMP)-2 and insulin growth factor binding protein (IGFBP)7, detect AKI before serum creatinine in critically ill patients and are associated with long-term adverse outcomes. Whether these markers can be used to predict renal and cardiovascular outcomes in patients undergoing angiography is yet unknown. We have been recently funded by the Department of Veterans Affairs to conduct a multicenter, randomized, clinical trial in 7,680 high-risk patients undergoing angiography to compare the effectiveness of intravenous sodium bicarbonate with isotonic sodium chloride, and oral N- acetylcysteine with placebo, for the prevention of serious adverse outcomes associated with CIAKI. The NIDDK has funded an associated biorepository to examine known and yet-to-be identified biomarkers for CIAKI. We propose to leverage these resources to conduct an ancillary observational study entitled Biomarker Effectiveness Analysis in Contrast Nephropathy (BEACON). Using urine and plasma samples obtained before and at four hours after angiography in 2000 subjects, we will address two specific aims. Aim 1 will examine the accuracy of urinary TIMP-2, IGFBP7, and select other plasma biomarkers in predicting the composite renal outcome of death, dialysis dependence, or persistent renal injury at day 90 after contrast exposure (Aim 1a); biomarker reclassification of risk for adverse renal outcomes and develop a risk score (Aim 1b); and predicting the progression of chronic kidney disease (Aim 1c). Aim 2 will examine the accuracy of urinary TIMP-2 and IGFBP7 in predicting the composite outcome of hospitalization with acute coronary syndrome; heart failure; cerebrovascular accident; or all-cause mortality within 90 days (Aim 2a); and biomarker reclassification of risk for cardiovascular events (Aim 2b). The proposed work will advance NIDDK’s mission of early detection, risk-stratification, and prognostication of CIAKI. It will provide new scientific knowledge on using biomarkers to monitor patients undergoing angiography and will have a high impact on clinical practice, physicians, and policy makers.

摘要 – 对比肾病的生物标志物有效性分析 对比剂诱发的急性肾损伤（CIAKI）是慢性肾病患者发生的一种严重并发症 接受血管造影并与不良肾脏和心血管结局相关的疾病。 解决接受血管造影的高危患者中仍然存在的两个关键问题：第一，早期发现。 对比剂暴露后的 CIAKI 是有问题的，因为血清肌酐升高或尿量下降 第二，长期不良的早期风险分层。 事件也是有问题的，因为现有的风险预测模型仅具有适度的预测价值。 在肌酐之前检测亚临床 CIAKI 并有助于风险分层的生物标志物的可用性将 改变一级和二级预防策略 FDA 最近批准了两本小说，受到高度评价。 用于早期检测 AKI 的敏感的尿细胞周期停滞生物标志物 我们已经证明这些生物标志物： 金属蛋白酶组织抑制剂（TIMP）-2和胰岛素生长因子结合蛋白（IGFBP）7，检测AKI 危重患者的血清肌酐水平是否与长期不良结局相关。 这些标志物可用于预测接受血管造影的患者的肾脏和心血管结果 目前尚不清楚。我们最近得到了退伍军人事务部的资助，开展了一项多中心研究， 对 7,680 名接受血管造影的高危患者进行的随机临床试验，以比较以下方法的有效性 静脉注射碳酸氢钠和等渗氯化钠，口服 N-乙酰半胱氨酸和安慰剂，用于 预防与 CIAKI 相关的严重不良后果 NIDDK 资助了相关项目。 我们建议利用这些生物样本库来检查已知的和尚未确定的 CIAKI 生物标志物。 进行题为“对比生物标志物有效性分析”的辅助观察研究的资源 肾病 (BEACON) 使用血管造影之前和之后四小时获得的尿液和血浆样本。 在 2000 名受试者中，我们将解决两个具体目标 1 将检查尿液 TIMP-2 的准确性， IGFBP7，并选择其他血浆生物标志物来预测死亡、透析的复合肾脏结局 依赖性，或造影剂暴露后第 90 天的持续性肾损伤（目标 1a）； 不良结果的肾脏风险并制定风险评分（目标 1b）并预测慢性病的进展； 肾脏疾病（目标 1c）。目标 2 将检查尿液 TIMP-2 和 IGFBP7 在预测肾病方面的准确性。 因急性冠脉综合征住院的综合结果；或 90 天内全因死亡率（目标 2a）以及心血管事件风险的生物标志物重新分类 （目标 2b）。拟议的工作将推进 NIDDK 的早期发现、风险分层和预防的使命。 CIAKI 的预后将为使用生物标志物监测患者提供新的科学知识。 接受血管造影将对临床实践、医生和政策制定者产生重大影响。