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

脓毒症肾病例表型分析和早期急性肾损伤手术 (PReCISE AKI)

• 批准号: 9392718
• 负责人: John A Kellum
• 金额: $ 41.38万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9392718
• 关键词: Abscess; Acute; Acute Renal Failure with Renal Papillary Necrosis; Acute myocardial infarction; Affect; Age; Biological Markers; Biopsy; Blood; Cardiac Surgery procedures; Cessation of life; Chronic Kidney Failure; Clinical; Collaborations; Complex; Computerized Medical Record; Consent; Consent Forms; Country; Creatinine; Critical Illness; Data; Development; Disease; Early identification; Emergency Medicine; Enrollment; Ethics; Etiology; Event; Experimental Models; Foundations; Functional disorder; Goals; Hemorrhage; Hospital Mortality; Hospitals; Human; Incidence; Individual; Infarction; Intervention; Intestines; Kidney; Kidney Transplantation; Laparotomy; Link; Medical; Medical center; Medicare; Methods; Modeling; Myocardial Infarction; Nature; Operative Surgical Procedures; Outcome; Patients; Pennsylvania; Perforation; Performance; Phenotype; Population; Procedures; Protocols documentation; Recovery; Recruitment Activity; Relapse; Research; Resolution; Risk; Sampling; Sepsis; Services; Site; Standardization; Surgeon; Syndrome; System; Testing; Time; Tissues; Trauma; Ultrasonography; Universities; Urine; Work; adjudicate; adjudication; base; biobank; clinical phenotype; cohort; cost; epidemiology study; experience; follow-up; high risk; improved; innovation; mortality; novel marker; patient population; precision medicine; programs; response; virtual

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.

抽象的 急性肾脏损伤（AKI）的总体事件估计约为2-3/1000美国人口，类似于 急性心肌梗死的。但是，由于综合征的沉默性质，这可能是 低估。老年人受到不成比例的影响。在66-69岁的Medicare患者中， 例如，2011年的AKI率为每1,000名患者14.9，增加到18.8、26.4、35.9和49.6 分别针对70-74、75-79、80–84和85岁及以上的年龄及以上。同样的人口关系也存在 对于败血症和心脏手术等AKI的许多原因，AKI的两个主要原因。最近的证据 表明许多米勒形式的AKI也与增加医院死亡的风险增加有关。虽然 这种增加死亡率的原因尚未完全理解，这些研究和许多其他研究使 令人信服的论点是，发展为AKI的患者的死亡风险增加了 由于Aki本身。 关于人类AKI的基本机制，相对鲜为人知，已经写了很多关于 实验模型的局限性； AKI的科学基础很弱，AKI早期的组织是 几乎不存在。我们目前的理解是，长期结果与 慢性肾脏病（CKD）。这存在着与与纵向流行病学研究有关的迫切需求 生物样品（组织，血液和尿液），可以检验多种假设 这种疾病及其病理生理学。由于我们的基本 缺乏理解；对AKI的病理生理学的更多了解将允许发展新的 干预措施。 此应用，精确的AKI（败血症的表型肾脏病例和早期急性肾脏手术 伤害），将利用我们的招聘站点的六项优势：1。 宾夕法尼亚州西部14家医院的电子病历（EMR）； 2。生物标志物 早期识别AKI； 3。在医学，外科和 急诊医学服务，专门针对AKI； 4。现有的针对患者准确性和长期跟进的研究 - 在Aki中; 5。在生物群中的丰富经验，包括血液和尿液样本； 6。一个程序 方案为大型肾脏移植程序的肾脏活检。我们注意到，其中一些优势是 独特的 - 特别是，使用新型生物标志物富集和手术患者的入学率 术中活检。使用这些优势，我们旨在从一系列AKI的患者那里获得活检 综合征以安全且道德的方式，检验以下假设：AKI的特定临床表型具有 区分活检结果，然后将AKI的调整后病因与活检结果进行比较和临床 结果；并确定活检结果是否可以预测早期分辨率和随后的CKD风险。