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）： 这项特别的拨款申请是为了响应资助机会公告而提交的，该公告旨在建立急性肾损伤 (AKI) 自然史联盟，其主要目标是跟踪 AKI 患者在疾病急性期结束后的自然史与同时发生的相关对照患者进行比较。 AKI 是住院患者常见且严重的并发症。根据大型医疗保险数据库的信息，AKI 的发病率在过去几十年中急剧增加，表明病例数量每年增加 11%。尽管 AKI 的院内并发症已得到广泛研究，但 AKI 的长期后遗症，特别是其对导致终末期肾病的 CKD 发生和进展的贡献，尚未得到彻底评估。该提案的具体目标如下： 具体目标#1：在危重患者的长期前瞻性队列研究中，检查既往 AKI 病史对慢性肾脏病 (CKD) 进展的独立风险。我们假设，与入住重症监护室 (ICU) 的未诊断出 AKI 的受试者相比，诊断出 AKI 与 CKD 进展率较高（急性疾病恢复后）相关。具体目标#2：在危重患者的长期前瞻性队列研究中，检查既往 AKI 病史对氧化应激增加、慢性炎症和进行性心血管疾病发展的独立风险。我们假设，与 ICU 中未诊断 AKI 的患者相比，AKI 会导致氧化应激负担增加，并导致 ICU 受影响患者的慢性炎症反应和心血管风险状况恶化。具体目标#3：a) 比较生物标志物组在高危重症患者 AKI 早期诊断中的相对和综合预测能力； b) 确定相同的生物标志物组是否可以预测 AKI 的严重程度（需要肾脏替代治疗、无透析生存）和其他临床相关结果（死亡率和 ICU/医院住院时间）。我们假设：1) 包含肾脏特异性损伤标志物（例如尿液 IL-18、NGAL、F2-异前列烷和入组时获得的血清/尿液胱抑素 C）的生物标志物组将优于单一标志物。根据 AKIN 标准对 ICU 易感患者群体诊断 AKI； ii) 在预测 AKI 严重程度和其他临床相关结果方面，相同的生物标志物组将优于单一标志物。为了实现拟议的目标，我们将从独特且新颖的资源中招募 500 名受试者，即急性肺损伤诊断中生物标志物的验证 (VALID) 研究，随后是一个异质危重病人群的大型（2550 名受试者）前瞻性观察队列在 ICU 期间和剩余住院期间。