Protocolized Goal-directed Resuscitation of Septic Shock to Prevent AKI

描述（由申请人提供）：根据PAR-07-024，主要正在进行的NIDDK和NHLBI临床研究NIDDK的辅助研究，我们提议进行一项旨在检查脓毒症患者产生的急性肾损伤（AKI）自然史的研究。超过50%的重症aki患者存在脓毒症。3美国国立卫生研究院最近资助了一项早期脓毒症休克（P50 GM076659）的大型治疗试验。这项试验，早期感染性休克的治疗方案（ProCESS），将在19个中心随机分配1935名患者到三个不同的治疗组。研究ProCESS队列患者的机会为我们提供了一个历史性的机会，可以前瞻性地进行一项大型自然病史研究，以辅助一项广泛的多中心试验，这是最可能导致AKI的环境。我们的提案，脓毒性休克的目标导向复苏以预防急性肾损伤（进展AKI），将研究方案化复苏对AKI发展的影响。我们还试图探索干预效果的潜在机制，并评估肾损伤和修复的标志物，以帮助选择患者进行未来的干预试验。为了与NIH路线图保持一致，为了了解这项工作的临床效用，我们将建立一个考虑生物标志物和临床变量的临床风险预测模型。我们将这些任务安排为三个具体目标：验证方案化复苏预防或减轻AKI严重程度或持续时间的假设，2。2 .确定哪些病理生理紊乱（炎症、缺血、氧化应激和凝血/血栓形成）联合或单独与AKI的发生有关；在脓毒症的情况下，确定生物标志物是否可以预测AKI和AKI的恢复。我们的部分研究将包括家访，我们选择将家访与母试验分开进行，以避免辅助研究造成的任何入组损失。我们将在出院后重新联系过程受试者，并在三个时间点对他们进行随访。通过这一部分的研究，我们将确定方案化复苏是否在改善整个队列的长期结果（生存、肾脏恢复、减缓CKD进展）以及通过生物标志物（生物标志物阳性AKI）有AKI证据的亚人群中更有效。

DESCRIPTION (provided by applicant): Under PAR-07-024, Ancillary Studies to Major Ongoing NIDDK and NHLBI Clinical Research Studies NIDDK, we are proposing to conduct a study which aims to examine the natural history of Acute Kidney Injury (AKI) arising in patients with sepsis. Sepsis is found in more than 50% of critically-ill patients with AKI.3 The NIH has recently funded a large therapeutic trial of early septic shock (P50 GM076659). This trial, Protocolized Care for Early Septic Shock (ProCESS), will randomize 1935 patients at 19 centers to three different treatment arms. The opportunity to study patients from the ProCESS cohort presents us with an historic opportunity to prospectively conduct a large natural history study ancillary to an extensive multi-center trial in a setting which is most likely to result in AKI. Our proposal, Protocolized Goal-directed Resuscitation of Septic Shock to Prevent Acute Kidney Injury (ProGReSS AKI), will examine the effect of protocolized resuscitation on the development of AKI. We also seek to explore mechanisms underlying the effect of the intervention and to evaluate markers of renal injury and repair in order to help select patients for future interventional trials. 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 biomarkers and clinical variables. We have organized these tasks as three specific aims: 1. test the hypothesis that protocolized resuscitation prevents or lessens severity or duration of AKI, 2. determine which pathophysiologic derangements (inflammation, ischemia, oxidative stress, and coagulation/ thrombosis), in combination or individually, are associated with the development of AKI, and 3. determine whether biomarkers can predict AKI and recovery from AKI in the setting of sepsis. Part of our study will include home visits, for which we have opted to separate from the parent trial so as to avoid any loss of enrollment incurred by the ancillary study. We will re-contact ProCESS subjects after discharge from the hospital and follow them at five time points for three years. Through this part of the study, we will determine if protocolized resuscitation is more effective in improving long term outcomes (survival, renal recovery, reduced progression of CKD) in the entire cohort as well as in the subpopulation that has evidence of AKI by biomarkers (biomarker-positive AKI).