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)
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