Phenotyping REnal Cases In Sepsis and surgery for Early Acute Kidney Injury (PReCISE AKI)

摘要 据估计，急性肾损伤（阿基）的总体发病率约为2-3/1000美国人口，与 急性心肌梗塞的症状。然而，由于该综合征的沉默性质，这可能是一个 低估。老年人受到的影响不成比例。在66-69岁的医疗保险患者中， 例如，2011年的阿基发生率为14.9/1000例患者，分别增加到18.8、26.4、35.9和49.6 分别为70-74岁、75-79岁、80-84岁和85岁及以上。同样的人口关系也存在 对于许多阿基的原因，如脓毒症和心脏手术，阿基的两个主要原因。最近的证据 提示，较轻微的阿基也与医院死亡风险增加有关。虽然 死亡率上升的原因尚不完全清楚，这些研究和许多其他研究表明， 一个令人信服的论点是，发生阿基的患者死亡风险额外增加， 由于阿基本身的原因。 对人类阿基的潜在机制知之甚少， 实验模型的局限性;阿基的科学基础薄弱，早期阿基的组织 几乎不存在我们目前的理解是，长期成果与发展有关， 慢性肾病（CKD）。因此，迫切需要进行纵向流行病学研究， 生物样本（组织、血液和尿液），可用于检验关于 这种疾病及其病理生理学。由于我们的基本治疗方法， 缺乏了解;更好地了解阿基的病理生理学将允许开发新的 干预措施。 此应用程序，PReCISE阿基（败血症和早期急性肾脏手术中的肾脏病例表型分析 伤），将发挥我们招聘网站的六大优势：1.建立阿基警报系统， 在宾夕法尼亚州西部的14家医院标准化电子病历（EMR）; 2.的生物标志物 阿基的早期识别; 3.建立了医疗、外科和 紧急医疗服务，专门针对阿基; 4.现有的患者招募和长期随访研究- 在阿基; 5.丰富的生物库经验，包括血液和尿液样本; 6.的程序 大型肾移植项目的肾活检协议我们注意到，其中一些优势是 独特的-特别是，使用新的生物标志物富集和登记的手术患者， 术中活检。利用这些优势，我们的目标是获得患有一系列阿基的患者的活检 以安全和道德的方式，测试阿基的特定临床表型具有以下假设： 不同的活检结果，然后将判定的阿基病因与活检结果和临床 结果;并确定活检结果是否可以预测CKD的早期解决和随后的风险。

ABSTRACT The overall incidence of acute kidney injury (AKI) is estimated to be about 2-3/1000 US population, similar to that of acute myocardial infarction. However, because of the silent nature of the syndrome, this is likely an underestimate. Older individuals are disproportionately affected. Among Medicare patients age 66–69, for example, the rate of AKI in 2011 was 14.9 per 1,000 patients, increasing to 18.8, 26.4, 35.9, and 49.6 respectively for ages 70–74, 75–79, 80–84, and 85 and older. This same demographic relationship also exists for many causes of AKI such as sepsis and cardiac surgery, the two leading causes of AKI. Recent evidence suggests that much milder forms of AKI are also associated with increased risk of hospital mortality. Although the reasons for this increased mortality are not fully understood, these studies and many others make a compelling argument that patients who develop AKI are at an additional increased risk of death that is in some way due to AKI itself. Relatively little is known about the underlying mechanisms of AKI in humans and much has been written about the limitations of experimental models; the scientific foundation for AKI is weak and tissue from early AKI is virtually nonexistent. Our current understanding is that long-term outcomes are linked to development of chronic kidney disease (CKD). Thus exists a critical need for longitudinal epidemiologic studies linked to biologic samples (tissue, blood and urine) that would allow the testing of multiple hypotheses as to the nature of this disease and its pathophysiology. Prior interventions for the treatment of AKI have failed due to our basic lack of understanding; greater understanding of the pathophysiology of AKI will permit development of new interventions. This application, PReCISE AKI (Phenotyping REnal Cases In Sepsis and surgery for Early Acute Kidney Injury), will leverage six strengths of our recruitment site: 1. An established AKI alerting system within the electronic medical record (EMR) standardized across 14 hospitals in western Pennsylvania; 2. Biomarkers for early identification of AKI; 3. Established research and clinical collaboration across medical, surgical and emergency medicine services, specifically for AKI; 4. Existing studies for patient accrual and long-term follow- up in AKI; 5. Extensive experience with biobanking including blood and urine samples; 6. A program for protocolized kidney biopsies for a large kidney transplant program. We note that some of these strengths are unique—particularly, the use of novel biomarker enrichment and enrollment of surgical patients with intraoperative biopsies. Using these strengths, we aim to obtain biopsies from patients with a range of AKI syndromes in a safe and ethical manner, test the hypothesis that specific clinical phenotypes of AKI have differing biopsy findings and then compare adjudicated etiology of AKI to biopsy results and to clinical outcomes; and determine whether biopsy findings can predict early resolution and subsequent risk for CKD.