Biomarker Collection and Analysis in the PRESERVE Trial Cohort

PRESERVE 试验队列中的生物标志物收集和分析

• 批准号: 8479591
• 负责人: PAUL M PALEVSKY
• 金额: $ 77.32万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8479591
• 关键词: Acetylcysteine; Acute Renal Failure with Renal Papillary Necrosis; Address; Adverse effects; Angiography; Attenuated; Bicarbonates; Biological Markers; Blood; Cardiac Surgery procedures; Caring; Cessation of life; Chronic Kidney Failure; Clinical; Clinical Trials; Collection; Commit; Creatinine; Data; Deterioration; Development; Diagnosis; Diagnostic; Dialysis procedure; Dyes; Early Diagnosis; Effectiveness of Interventions; Evaluation; Funding; Future; Health; Heart failure; Hour; Injury; Intervention; Intravenous; Investigation; Isotonic Exercise; Kidney; Kidney Diseases; Lead; Measures; Oral; Outcome; Participant; Patients; Pharmaceutical Preparations; Placebos; Prevention; Preventive; Preventive Intervention; Procedures; Randomized Clinical Trials; Renal function; Research; Research Personnel; Resources; Risk; Risk Factors; Sampling; Sepsis; Serum; Sodium Bicarbonate; Sodium Chloride; Staging; Supportive care; Tubular formation; Urine; Veterans; adverse outcome; base; biobank; cell injury; clinical Diagnosis; cohort; compare effectiveness; cooperative study; cost effective; high risk; improved; intervention effect; prevent; programs

DESCRIPTION (provided by applicant): Contrast-induced acute kidney injury (CIAKI) is a common form of iatrogenic renal disease that is associated with serious, adverse, short- and long-term outcomes. While certain risk factors for CIAKI (e.g., chronic kidney disease, heart failure) are well known, our current capacity to accurately predict which patients are going to develop CIAKI based on these factors is limited. This results in the need to implement resource-intensive preventive care on a widespread basis, rather than in the sub-group of patients at greatest risk. Furthermore, the clinical diagnosis of CIAKI, which is based on small increments in serum creatinine (SCr), is delayed by up to 2-5 days following contrast administration because elevations in SCr reflect the functional effects of renal injury rather than tubular cell damage itself. Identifying serum and/or urine biomarkers that effectively stratify patients' risk fr CIAKI and diagnose its incipient stages could help concentrate the use of preventive care in those patients most likely to derive benefit and facilitate the provision of supportive care early after renal injury in order to mitigate further tubular damage and attenuate the risk for serious, adverse, longer-term outcomes. Our group has been funded by the Department of Veterans Affairs to conduct a multicenter, randomized, clinical trial of 7,680 high-risk patients with chronc kidney disease undergoing angiography to compare the effectiveness of intravenous (IV) isotonic sodium bicarbonate with IV isotonic sodium chloride and oral N- acetylcysteine with oral placebo for the prevention of serious adverse outcomes (i.e., death, need for dialysis, persistent decline in kidney function at 90 days) associated with CIAKI. We propose to leverage the substantial resources committed to this large trial to establish a biorepository of blood and urine samples collected from study participants. This biorepository, which will be available as a common-use resource for future investigation of putative and yet-to-be identified biomarkers of CIAKI, will be used for the current proposal to address the following specific aims: Specific aim 1: To assess whether serum and/or urine biomarkers measured prior to angiography are able to stratify the risk of developing: a) CIAKI and; b) serious, adverse, longer-term outcomes (90-day death, need for dialysis, persistent renal injury). Specific aim 2: To assess whether serum and/or urine biomarkers measured 4 hours following angiography: a) permit the early diagnosis of CIAKI and; b) are able to stratify the risk of developing serious, adverse, longer-term outcomes (90-day death, need for dialysis, persistent renal injury) Specific aim 3: To examine the effect of the clinical trial interventions (i.e., IV isotonic sodium bicarbonate and oral N-acetylcysteine) on serum and urine biomarkers 4 hours following angiography and their capacity to predict the development of: a) CIAKI and; b) serious, adverse, longer-term outcomes

描述（由申请人提供）：对比诱发的急性肾损伤（CIAKI）是医源性肾脏疾病的常见形式，与严重，不良，短期和长期结局有关。尽管Ciaki的某些危险因素（例如，慢性肾脏疾病，心力衰竭）是众所周知的，但我们目前可以准确预测哪些患者将根据这些因素进行Ciaki的能力是有限的。这导致需要广泛实施资源密集型预防保健，而不是在风险最大的患者子组中。此外，Ciaki的临床诊断基于血清肌酐（SCR）的较小增量，在对比度给药后最多2-5天延迟了2-5天，因为SCR的升高反映了肾脏损伤的功能效应，而不是管状细胞损伤。识别有效地分层Ciaki的患者风险并诊断其初期阶段的血清和/或尿液生物标志物可以帮助集中精力在这些患者中使用预防性护理，最有可能获得福利并促进肾脏损伤后早期提供支持性护理，以减轻肾小管损害，以缓解进一步的损害，并降低严重的风险严重，不利，更长期的过时，更长期的过时。 Our group has been funded by the Department of Veterans Affairs to conduct a multicenter, randomized, clinical trial of 7,680 high-risk patients with chronc kidney disease undergoing angiography to compare the effectiveness of intravenous (IV) isotonic sodium bicarbonate with IV isotonic sodium chloride and oral N- acetylcysteine with oral placebo for the prevention of serious adverse outcomes （即死亡，需要透析，90天后肾脏功能的持续下降）与Ciaki相关。我们建议利用致力于这项大型试验的大量资源来建立血液和尿液的生物措施 从研究参与者那里收集的样本。该生物座席将作为通用资源可用，用于未来对Ciaki的假定和尚未确定的生物标志物进行调查，将用于当前提案，以解决以下特定目的：具体目的1：评估血清和/或尿液生物标志物在血管造影之前测量的血清和/或尿液生物标志物是否能够对发展的风险进行分解：Ciaki和A）A）A）A）A）A）A）； b）严重，不良，长期的结局（90天死亡，需要透析，持续性肾脏损伤）。具体目的2：评估血管造影后4小时测量的血清和/或尿液生物标志物是否：a）允许早期诊断Ciaki； b) are able to stratify the risk of developing serious, adverse, longer-term outcomes (90-day death, need for dialysis, persistent renal injury) Specific aim 3: To examine the effect of the clinical trial interventions (i.e., IV isotonic sodium bicarbonate and oral N-acetylcysteine) on serum and urine biomarkers 4 hours following angiography and their capacity to predict the development of: a) ciaki和; b）严重，不利，长期的结果