Novel Biomarkers in Cardiac Surgery to Detect Acute Kidney Injury

心脏手术中检测急性肾损伤的新型生物标志物

• 批准号: 8458526
• 负责人: Chirag R Parikh
• 金额: $ 72.63万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8458526
• 关键词: Acute Renal Failure with Renal Papillary Necrosis; Adult; Albuminuria; Biological Markers; Blood specimen; Cardiac Surgery procedures; Cardiovascular Diseases; Caring; Cessation of life; Child; Childhood; Chronic Kidney Failure; Clinical; Clinical Trials; Complication; Creatinine; Decision Making; Dialysis procedure; Discrimination; Early Diagnosis; End stage renal failure; Enrollment; FABP1 gene; Filtration; Future; Gelatinase A; Goals; Grant; Health; Hospitals; Hour; Hypertension; Incidence; Individual; Informed Consent; Injury; Interleukin-18; Investments; Kidney; Knowledge; Length of Stay; Link; Literature; Measurement; Measures; Methods; Microalbuminuria; Modeling; Morbidity - disease rate; Mortality Decline; Operative Surgical Procedures; Outcome; Parents; Patients; Persons; Phase; Plasma; Plasma Albumin; Postoperative Period; Premature Mortality; Pump; Renal function; Reporting; Research; Resources; Risk; Safety; Sampling; Serum; Statistical Methods; Surgeon; Telephone; Testing; Translational Research; Troponin T; Urine; Visit; administrative database; biobank; clinical application; cohort; follow-up; improved; information gathering; innovation; mortality; novel; parent grant; post gamma-globulins; therapy development; tool; urinary

DESCRIPTION (provided by applicant): Acute kidney injury (AKI) is common after cardiac surgery and impacts short and long-term mortality. The parent grant, RO1 (HL-085757), focused on developing novel tools for assessment of structural kidney damage and comparing new tests to the traditional measurement of serum creatinine, which is a measure of kidney filtration. We created the Translational Research Investigating Biomarker Endpoints (TRIBE) consortium and fulfilled the goals of all of the specific aims of the grant and reported results on several novel urine and plasma biomarkers of kidney injury, such as urine IL-18, urine and plasma NGAL, urine albumin, plasma BNP, and plasma cystatin C. We prospectively enrolled over 2000 adults and children undergoing cardiac surgery at 9 centers and developed a robust sample biorepository linked to clinical variables. In this competitive renewal, we will enrich our cohort y gathering information on long-term outcomes in adult and pediatric patients through continued phone calls, in-person visits, and linkages of the TRIBE cohort to national administrative databases. We will also perform measures of three promising urine biomarkers (KIM- 1, L-FABP and urine cystatin C) and two plasma biomarkers (CK-MB, high sensitivity troponin-T) on the samples stored in our biorepository. With a total of 11 measured biomarkers (from the parent and renewal grants), we will create multi-marker panels for predicting AKI and other outcomes using emerging and innovative statistical methods. We hypothesize that the pre-operative and post-operative biomarkers will not only predict AKI, but also will predict longer-term complications years later, such as chronic kidney disease, end-stage renal disease, and death. Additionally, we hypothesize those patients with high biomarker levels, but no evidence of clinical AKI (subclinical AKI); will also have poor long-term outcomes. The availability of reliabl clinical models for these short and long-term outcomes will assist with informed decision making, adequate planning for surgeons, post-discharge management, and inform future clinical trials. Our primary research aims are: Aim 1: To ascertain long-term outcomes associated with AKI after cardiac surgery in adults and children. Aim 2: To construct a multi-marker biomarker panel to improve risk prediction of outcomes in adults and children.

描述（由申请人提供）：急性肾损伤（阿基）在心脏手术后很常见，会影响短期和长期死亡率。母基金RO 1（HL-085757）专注于开发用于评估结构性肾损伤的新工具，并将新测试与传统的血清肌酐测量进行比较，血清肌酐是肾脏滤过的一种测量方法。我们创建了转化研究调查生物标志物终点（TRIBE）联盟，并实现了该资助的所有具体目标，并报告了几种新的尿液和血浆肾损伤生物标志物的结果，如尿液IL-18，尿液和血浆NGAL，尿液白蛋白，血浆BNP和血浆胱抑素C。我们前瞻性招募了9个中心接受心脏手术的2000多名成人和儿童，并开发了一个与临床变量相关的强大样本生物储存库。在这次竞争性更新中，我们将通过持续的电话、亲自访问以及TRIBE队列与国家行政数据库的链接，丰富我们收集成人和儿童患者长期结局信息的队列。我们还将对储存在我们的生物储存库中的样本进行三种有希望的尿液生物标志物（KIM- 1、L-FABP和尿胱抑素C）和两种血浆生物标志物（CK-MB、高灵敏度肌钙蛋白-T）的测量。共有11个测量的生物标志物（来自母公司和续期赠款），我们将使用新兴和创新的统计方法创建多标志物面板，用于预测阿基和其他结果。我们假设术前和术后生物标志物不仅可以预测阿基，还可以预测多年后的长期并发症，如慢性肾脏疾病、终末期肾脏疾病和死亡。此外，我们假设那些生物标志物水平高，但没有临床阿基（亚临床阿基）证据的患者也将具有不良的长期结局。这些短期和长期结局的可靠临床模型的可用性将有助于明智的决策，外科医生的充分规划，出院后管理，并为未来的临床试验提供信息。我们的主要研究目的是：目的1：确定成人和儿童心脏手术后与阿基相关的长期结局。目的2：构建一个多标志物生物标志物组，以改善成人和儿童结局的风险预测。