Biological Markers of Recovery for the Kidney

描述(由申请人提供)：NIDDK与退伍军人事务部合作研究计划最近资助了一项针对ARF的大型治疗试验。这项名为ARF试验网络(ATN)研究CSP530的试验将在27个中心随机对1164名患者进行常规和高剂量肾脏替代治疗。根据计划公告PAR-04-078用于NIDDK资助的临床试验的辅助研究，我们建议在ATN-CSP 530研究中增加一组肾脏恢复的候选生物标记物(BioMark)的评估。初步证据表明，遗传、炎症和临床因素都起到了作用，人们对肾脏替代疗法的提供方式是否会影响临床进程的问题越来越感兴趣。 BioMark的中心目标是更好地了解炎症和氧化应激这两个关键途径在ARF后存活和肾功能恢复中的作用。我们还将研究遗传变异，不仅是编码炎症介质的基因，还包括损伤到修复连续体的其他关键组成部分。此外，我们将通过尿质谱检查寻找肾脏损伤和修复的新标记物。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价值，我们将建立一个临床风险预测模型，该模型将考虑血浆介质水平、尿标记物、遗传和临床变量。我们将使用ATN-CSP 530试验队列作为新建立的ARF患者的初始队列。对于大多数分析，我们建议研究ATN-CSP530试验队列中同意血液样本和DNA库的整个部分(815名患者)。对于需要系列样本和尿样的分析，我们建议研究在5个地点登记的同意额外样本采集的试验患者子集(208名患者)

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)