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

摘要 急性肾损伤(AKI)的总发病率估计约为2-3/1000美国人口，类似于 急性心肌梗死。然而，由于该综合征的沉默性质，这很可能是一种 低估了。年龄较大的人受到的影响更大。在66-69岁的联邦医疗保险患者中， 例如，2011年的AKI患病率为每千名患者14.9例，分别增至18.8、26.4、35.9和49.6 年龄分别为70-74岁、75-79岁、80-84岁和85岁及以上。同样的人口统计关系也存在 AKI的许多原因，如败血症和心脏手术，是AKI的两个主要原因。最近的证据 这表明，病情较轻的AKI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，这些研究和其他许多研究使 令人信服的论点是，发生AKI的患者死亡风险额外增加，在某些情况下 这要归功于AKI本身。 对人类AKI的潜在机制知之甚少，关于AKI的文章也很多 实验模型的局限性；AKI的科学基础薄弱，早期AKI的组织 几乎不存在。我们目前的理解是，长期结果与发展 慢性肾病(CKD)。因此，迫切需要进行与以下疾病有关的纵向流行病学研究 生物样本(组织、血液和尿液)，允许对自然界的多种假说进行检验 这种疾病及其病理生理学。以前治疗急性骨髓炎的干预措施都失败了，因为我们的基本 缺乏了解；对AKI病理生理学的更多了解将有助于开发新的 干预措施。 AKI在脓毒症及早期急性肾功能衰竭手术中的应用 受伤)，将利用我们招聘网站的六个优势：1.在 宾夕法尼亚州西部14家医院的电子病历(EMR)标准化；2.生物标记物 早期识别AKI；3.建立内科、外科和临床领域的研究和临床协作 急诊医疗服务，特别针对AKI；4.关于患者收益和长期随访的现有研究-- 在AKI工作；5.有丰富的生物库工作经验，包括血液和尿液样本；6.有 一项大型肾移植计划的肾活检标本。我们注意到，这些优势中的一些是 独特-特别是使用新的生物标记物丰富和登记外科患者与 术中活组织检查。利用这些优势，我们的目标是从一系列AKI患者身上获得活组织检查 以安全和伦理的方式，验证AKI特定临床表型具有 不同的活检结果，然后将判定的AKI病因与活检结果和临床进行比较 结果；并确定活检结果是否可以预测CKD的早期缓解和随后的风险。

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.