Biological Markers of Recovery for the Kidney

描述（由申请人提供）：NIDDK 与 VA 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 的试验将随机分配 27 个中心的 1164 名患者接受正常剂量肾脏替代治疗与高剂量肾脏替代治疗。根据 NIDDK 资助的临床试验辅助研究的计划公告 PAR-04-078，我们建议通过评估一组候选肾脏恢复生物标志物 (BioMaRK) 来增强 ATN-CSP 530 研究。初步证据表明遗传、炎症和临床因素都发挥了作用，并且人们越来越关注肾脏替代治疗的提供方式是否影响临床病程的问题。 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 后肾功能存活和恢复中的作用。我们还将研究遗传变异，不仅包括编码炎症介质的基因，还包括损伤修复连续体的其他关键组成部分。此外，我们将通过尿液质谱检查寻找肾损伤和修复的新标志物。最后，根据 NIH 路线图，为了了解这项工作的临床效用，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、尿液标记物、遗传和临床变量。我们将使用 ATN-CSP 530 试验队列作为新出现 ARF 患者的初始队列。对于大多数分析，我们建议研究同意血液样本和 DNA 库的 ATN-CSP530 试验队列的整个部分（815 名患者）。对于需要连续样本和尿液样本的分析，我们建议研究在 5 个地点招募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)