Biological Markers of Recovery for the Kidney

肾脏恢复的生物标志物

• 批准号: 7646517
• 负责人: John A Kellum
• 金额: $ 34.01万
• 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/7646517
• 关键词: Acute Kidney Failure; Acute Kidney Tubular Necrosis; Ancillary Study; Biological; Biological Markers; Blood specimen; Clinical; Clinical Markers; Clinical Trials; Code; Cohort Studies; Combined Modality Therapy; Consent; DNA Library; Development; Dialysis procedure; Dose; Drug Formulations; Enrollment; Evaluation; Functional disorder; Funding; Genes; Genetic; Genetic Markers; Genetic Variation; Goals; Grouping; Hospitals; Human; Inflammation; Inflammation Mediators; Inflammatory; Injury; Intervention; Kidney; Lasers; Left; Mass Spectrum Analysis; Measures; Mediator of activation protein; Modality; Modeling; Molecular Profiling; NIH Program Announcements; National Institute of Diabetes and Digestive and Kidney Diseases; Outcome; Oxidative Stress; Pathway interactions; Patient Discharge; Patients; Pattern; Plasma; Play; Probability; Proteomics; Randomized; Recovery; Renal Replacement Therapy; Renal function; Research Personnel; Risk; Role; Sampling; Series; Site; Specimen; Surface; Testing; Therapy Clinical Trials; Time; Translational Research; United States National Institutes of Health; Upper arm; Urine; Validation; Veterans; Weight; Work; base; cohort; cooperative study; dosage; inflammatory marker; injury and repair; interest; novel marker; partial recovery; programs; protein expression; repaired; repository; sample collection; therapeutic target

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，最近资助了一项大型ARF治疗试验。这项试验被称为ARF试验网络（ATN）研究CSP 530，将在27个中心随机分配1164名患者接受正常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项目公告PAR-04-078，我们建议通过评价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，人们越来越关注肾脏替代治疗的方式是否会影响临床病程。 BioMaRK的中心目标是更好地了解两个关键途径，炎症和氧化应激，在ARF后的生存和肾功能恢复中的作用。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-修复连续体的其他关键组成部分中。此外，我们将通过尿液的质谱检测来寻找新的肾损伤和修复的标志物。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性，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试验队列作为新发ARF患者的初始队列。对于大多数分析，我们建议研究ATN-CSP 530试验队列中同意血液样本和DNA库的整个部分（815例患者）。对于需要系列样本和尿液样本的分析，我们建议研究在5个研究中心入组并同意额外样本采集的试验患者子集（208例患者）