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: 10223906
• 负责人: John A Kellum
• 金额: $ 30万
• 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 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10223906
• 关键词: Abscess; Acute; Acute Renal Failure with Renal Papillary Necrosis; Acute myocardial infarction; Affect; Age; Biological; 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; Injury to Kidney; Intervention; Intestines; Kidney; Kidney Transplantation; Laparotomy; Link; Longterm Follow-up; Medical; Medical center; Medicare; Methods; Modeling; Myocardial Infarction; Nature; Operative Surgical Procedures; Outcome; Patients; Pennsylvania; Perforation; Performance; Phenotype; Population; Procedures; Protocols documentation; Recovery; Relapse; Research; Resolution; Risk; Sampling; Sapphire; Sepsis; Services; Site; Standardization; Surgeon; Syndrome; System; Testing; Time; Tissues; Topaz; Trauma; Ultrasonography; Universities; Urine; Work; adjudicate; adjudication; base; biobank; clinical phenotype; cohort; cost; early detection biomarkers; epidemiology study; experience; high risk; improved; innovation; kidney biopsy; mortality; mortality risk; novel marker; participant enrollment; patient population; precision medicine; programs; recruit; 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 急性肾损伤 (AKI) 的总体发病率估计约为 2-3/1000 美国人口，类似于 然而，由于该综合征的隐匿性，这很可能是一种急性心肌梗塞。 66-69 岁的老年人受到的影响不成比例。 例如，2011年AKI发生率为每1000名患者14.9例，增加至18.8例、26.4例、35.9例和49.6例 分别针对 70-74 岁、75-79 岁、80-84 岁和 85 岁及以上年龄段。 AKI 的多种原因，例如败血症和心脏手术，这是 AKI 的两个主要原因。 表明较轻微的 AKI 也与医院死亡风险增加有关。 死亡率增加的原因尚不完全清楚，这些研究和许多其他研究提出了 令人信服的论点是，在某些情况下，发生 AKI 的患者死亡风险会更高 原因是 AKI 本身。 人们对人类 AKI 的潜在机制知之甚少，但已有大量文献报道 实验模型的局限性；AKI 的科学基础薄弱，早期 AKI 的组织缺乏 我们目前的理解是，长期结果与发展有关，这一点实际上不存在。 因此，迫切需要进行与慢性肾脏病（CKD）相关的纵向流行病学研究。 生物样本（组织、血液和尿液），可用于测试有关性​​质的多种假设 由于我们的基础原因，之前治疗 AKI 的干预措施都失败了。 缺乏了解；对 AKI 的病理生理学有更深入的了解将有助于开发新的方法 干预措施。 此应用程序，PReCISE AKI（脓毒症肾病例表型分析和早期急性肾脏手术 伤害），将利用我们招聘网站的六大优势： 1. 内部建立的 AKI 警报系统 宾夕法尼亚州西部 14 家医院的电子病历 (EMR) 标准化；2. 生物标志物； AKI 的早期识别；3. 建立跨医学、外科和临床的研究和临床合作。 紧急医疗服务，特别是针对 AKI 的服务； 4. 现有的患者累积和长期随访研究； 具有 AKI 资格；5. 丰富的生物样本库经验，包括血液和尿液样本； 我们注意到，其中一些优势是用于大型肾移植计划的规范化肾活检。 独特的——特别是使用新型生物标志物富集和手术患者的入组 利用这些优势，我们的目标是从患有一系列 AKI 的患者中获取活检。 以安全和合乎道德的方式治疗综合征，检验 ​​AKI 的特定临床表型具有以下假设： 不同的活检结果，然后将 AKI 的病因学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 的早期缓解和后续风险。

项目成果

Acute kidney injury.

急性肾损伤。

• 发表时间: 2021-07-15
• 作者: Kellum, John A;Romagnani, Paola;Ashuntantang, Gloria;Ronco, Claudio;Zarbock, Alexander;Anders, Hans
• 通讯作者: Anders, Hans