Biological Markers of Recovery for the Kidney

肾脏恢复的生物标志物

• 批准号: 7031481
• 负责人: John A Kellum
• 金额: $ 36.74万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7031481
• 关键词: acute renal failure; biomarker; blood tests; clinical research; clinical trials; cooperative study; gene expression; hemodialysis; human subject; human therapy evaluation; inflammation; kidney function; mass spectrometry; mathematical model; oxidative stress; prognosis; protein quantitation /detection; surface enhanced laser desorption ionization; urine

DESCRIPTION (provided by applicant): NIDDK, together with the VA Cooperative Studies Program, recently funded a large therapeutic trial in ARF. This trial, known as the ARF Trial Network (ATN) study CSP530, will randomize 1164 patients at 27 centers to normal versus high-dose renal replacement therapy. Under the Program Announcement, PAR-04-078 for ancillary studies to NIDDK-funded clinical trials, we propose to augment the ATN-CSP 530 Study with an evaluation of a set of candidate biological markers of recovery for the kidney (BioMaRK). Preliminary evidence suggests genetic, inflammatory, and clinical factors all play a role and there is mounting interest in the question of whether the way in which renal replacement therapy is provided influences the clinical course. The central goal of BioMaRK is to better understand the role of two key pathways, inflammation and oxidative stress, in survival and recovery of renal function after ARF. We will also look at genetic variation, not only in genes coding for inflammatory mediators, but also other key components of the injury-to-repair continuum. Additionally, we will seek new markers of renal injury and repair by mass spectrometric examination of the urine. Finally, in keeping with the NIH Roadmap, in order to understand the clinical utility of this work, we will build a clinical risk prediction model that will consider plasma mediator levels, urine markers, genetic, and clinical variables. We will use the ATN-CSP 530 trial cohort as an inception cohort of patients with newly established ARF. For most analyses, we propose to study the entire portion of the ATN-CSP530 trial cohort that consents to the blood sample and DNA bank (815 patients). For analyses requiring serial samples and urine samples, we propose to study a subset of trial patients enrolled at 5 sites who consent to additional sample collection (208 patients)

描述（由申请人提供）：NIDDK与VA合作研究计划一起，最近在ARF中资助了一项大型治疗试验。该试验被称为ARF试验网络（ATN）研究CSP530，将在27个中心与正常肾脏替代疗法相比，将1164例患者随机分配为1164名患者。根据该计划公告，对NIDDK资助的临床试验的辅助研究PAR-04-078，我们建议通过评估肾脏（Biomark）恢复的一组候选生物学标志物来增强ATN-CSP 530研究。初步证据表明，遗传，炎症和临床因素都起作用，并且对提供肾脏替代疗法的方式是否影响临床过程的问题持续不断兴趣。 Biomark的核心目标是更好地了解ARF后肾功能的存活和恢复两种关键途径，炎症和氧化应激的作用。我们还将研究遗传变异，不仅在编码炎症介质的基因中，而且在损伤对修复连续体的其他关键组成部分中。此外，我们将通过对尿液的质谱检查来寻求肾脏损伤和修复的新标志。最后，为了与NIH路线图保持一致，为了了解这项工作的临床实用性，我们将建立一个临床风险预测模型，该模型将考虑等离子介体水平，尿液标记，遗传和临床变量。我们将使用ATN-CSP 530试验队列作为新成立的ARF患者组成。对于大多数分析，我们建议研究同意血液样本和DNA库（815例患者）的ATN-CSP530试验队列的整个部分。对于需要连续样品和尿液样品的分析，我们建议研究在同意额外样本收集（208名患者）的5个地点的试验患者的一部分