Impact of Acute Kidney Injury on Kidney Disease Progression

急性肾损伤对肾脏疾病进展的影响

• 批准号: 7547612
• 负责人: TALAT Alp IKIZLER
• 金额: $ 45万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-11 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7547612
• 关键词: Accounting; Acute; Acute Lung Injury; Acute Renal Failure with Renal Papillary Necrosis; Adult Respiratory Distress Syndrome; Affect; Amplifiers; Applications Grants; Biological Markers; Blood Pressure; Cardiovascular Diseases; Cardiovascular system; Caring; Cessation of life; Chronic; Chronic Kidney Failure; Cohort Studies; Communities; Complication; Creatinine; Critical Illness; Cystatins; Data; Data Collection; Databases; Development; Diabetes Mellitus; Diabetic Nephropathy; Diagnosis; Diagnostic; Dialysis procedure; Disease; Disease Progression; Early Diagnosis; Employee Strikes; End Point; End stage renal failure; Enrollment; F2-Isoprostanes; Functional disorder; Funding Opportunities; Future; Glomerular Filtration Rate; Hand; Hospitalization; Hospitals; Hypertension; Incidence; Inflammation; Inflammatory Response; Injury; Insulin Resistance; Intensive Care Units; Interleukin-18; Kidney; Kidney Diseases; Length of Stay; Longitudinal Studies; Medicare; Metabolic; Natural History; Nephrons; Numbers; Obesity; Outcome; Oxidative Stress; Patients; Phase; Physical Dialysis; Population; Prevalence; Prevention; Principal Investigator; Public Health; Race; Rate; Recording of previous events; Recovery; Recruitment Activity; Relative (related person); Reliance; Renal Replacement Therapy; Reporting; Research; Research Personnel; Resources; Risk; Risk Factors; Serum; Severities; Smoke; Stress; Time; Urine; Validation; base; cardiovascular risk factor; clinically relevant; cohort; experience; mortality; novel; outcome forecast; post gamma-globulins; programs; prospective; response

DESCRIPTION (provided by applicant): This particular grant application is submitted in response to the funding opportunity announcement that seeks to establish an Acute Kidney Injury (AKI) Natural History Consortium with the primary objective of following the natural history of patients with AKI after they finish the acute phase of their illness for comparison with concurrent relevant control patients. AKI is a common and serious complication in hospitalized patients. The incidence of AKI has increased dramatically over the past several decades based on information from large Medicare databases suggesting an increase in the number of cases by 11% per year. Whereas in-hospital complications of AKI have been extensively studied, the long-term sequelae of AKI, specifically its contribution to the development and progression of CKD leading to end-stage renal disease, have not been thoroughly evaluated. The specific aims of this proposal are as follows: SPECIFIC AIM #1: To examine the independent risk of prior history of AKI on chronic kidney disease (CKD) progression in a long-term prospective cohort study of critically ill patients. We hypothesize that the diagnosis of AKI is associated with a higher rate of progression of CKD (after the recovery of the acute illness) compared to no diagnosis of AKI in subjects admitted to intensive care unit (ICU). SPECIFIC AIM #2: To examine the independent risk of a prior history of AKI on the development of increased oxidative stress, chronic inflammation and progressive cardiovascular disease in a long-term prospective cohort study of critically ill patients. We hypothesize that AKI causes an increased oxidative stress burden and contributes to the chronic inflammatory response and worsened cardiovascular risk profiles of affected patients in the ICU compared to those without the diagnosis of AKI in the ICU. SPECIFIC AIM #3: a) To compare the relative and combined predictive capacities of a biomarker panel in the early diagnosis of AKI in high-risk critically ill patients; b) To determine if the same biomarker panel predicts the severity of AKI (need for renal replacement therapy, dialysis-free survival) and other clinically-relevant outcomes (mortality and ICU/hospital length of stay). We hypothesize that: 1) a biomarker panel that includes kidney specific markers of injury, such as urine IL-18, NGAL, F2- isoprostanes, and serum/urine cystatin C obtained at the time of enrollment will be superior to a single marker in diagnosing AKI based on AKIN criteria in a susceptible population of patients in the ICU; ii) Same biomarker panel will be superior to a single marker in predicting severity of AKI and other clinically-relevant outcomes. In order to achieve the proposed aims, we will recruit 500 subjects from a unique and novel resource, the Validation of biomarkers in Acute Lung Injury Diagnosis (VALID) study, a large (2550 subject) prospective observational cohort of a heterogeneous critically ill population followed throughout their ICU and remaining hospital stay.

描述（由申请人提供）： 这项特殊的赠款申请是为了响应旨在建立急性肾脏伤害（AKI）自然病史财团的资金机会公告，其主要目标是遵循AKI患者的自然历史，之后他们完成了疾病的急性阶段，以与同时的相关对照患者进行比较。 AKI是住院患者的常见且严重的并发症。在过去的几十年中，AKI的发生率大大增加，这是根据大型Medicare数据库的信息，表明每年的病例数量增加了11％。尽管已经对AKI的院内并发症进行了广泛的研究，但AKI的长期后遗症特别是其对CKD的发育和进展的贡献，导致终末期肾脏疾病，尚未得到彻底评估。该提案的具体目的如下：具体目的＃1：在长期对重症患者的前瞻性队列研究中，检查AKI先前的慢性肾脏疾病（CKD）进展的独立风险。我们假设AKI的诊断与CKD的进展率较高（急性疾病恢复后）相比，与接受重症监护病房（ICU）的受试者中未诊断为AKI相比。具体目的2：在一项长期对重症患者的前瞻性队列研究中，研究AKI的先前历史的独立风险，即氧化应激，慢性炎症和进行性心血管疾病的发展。我们假设AKI会导致增加的氧化应激负担，并导致慢性炎症反应，并与ICU中没有AKI诊断的患者相比，ICU中受影响患者的心血管风险特征恶化。特定目的＃3：a）比较生物标志物面板的相对和联合预测能力，以早期诊断为高危患者的AKI； b）确定相同的生物标志物面板是否可以预测AKI的严重性（需要肾脏替代疗法，无透析生存期）和其他与临床相关的结果（死亡率和ICU/医院住院时间）。我们假设：1）包括肾脏特定损伤标记的生物标志物小组，例如尿液IL-18，ngal，F2-异丙烷和血清/尿液/尿液囊蛋白C在招募时获得的疗程将优于基于AKI的单个标记，该标记是基于AKI的单个标记，该标记是基于AKI的诊断，该标记是根据iCU的患者诊断为ICU; ii）在预测AKI和其他与临床相关的结果的严重性方面，相同的生物标志物面板将优于单个标记。为了实现拟议的目的，我们将从独特而新颖的资源中招募500名受试者，急性肺损伤诊断中生物标志物的验证（有效）研究，这是一项大型（2550名受试者）的前瞻性观察群体，该群体是在整个ICU中随后遭受了异质性严重不良的人群，其ICU随后及其住院住院。