Biomarkers in Acute Kidney Injury

描述（由申请人提供）： 急性肾衰竭（ARF）是住院患者中越来越常见的并发症，并与极高的死亡率相关。通过测量血清肌酐来评估肾功能的经典方法是不敏感的，特别是在急性肾损伤（阿基）或ARF的情况下。这些研究的总体目标是开发和验证阿基的尿液和血清生物标志物，这些生物标志物将在比目前可能的更早阶段识别肾损伤的发作和严重程度。这些生物标志物的可用性将改善AKI患者和有AKI风险患者的护理，并有助于开发新的治疗和预防策略。在R21阶段，我们将建立收集和处理尿液的最佳方法，并开发定量分析尿液中以下潜在阿基生物标志物的分析能力：肾损伤分子-1（KIM-1）、中性粒细胞明胶酶相关脂质运载蛋白（NGAL）、基质金属蛋白酶-9（MMP-9）、谷胱甘肽-S-转移酶（α和pi-GST）、肌动蛋白、白细胞介素-18（IL-18）、富含半胱氨酸的蛋白61（Cyr-61）和胱抑素C。我们将在一项涉及200例AKI和非阿基患者的横断面研究中测试这些生物标志物识别阿基的能力。我们将使用统计技术，如多变量受试者工作特征曲线分析，以确定一组对阿基诊断敏感和特异的生物标志物，受试者工作特征曲线下的面积至少为0.85。我们还将从参与阿基前瞻性研究的六个合作中心发送给我们的样本中测量尿液生物标志物。在R21阶段成功实现目标的基础上，我们建议在R33阶段进行一项前瞻性研究，包括400例接受冠状动脉旁路移植术的患者和350例入住重症监护室的患者。在这些患者中，我们将检测R21阶段确定的一组生物标志物在血清肌酐检测前24小时前瞻性识别阿基的能力。阿基早期生物标志物的鉴定将是阿基风险患者临床护理的重要一步，并将极大地帮助研究预防和治疗的新策略。

DESCRIPTION (provided by applicant): Acute renal failure (ARF) is an increasingly common complication in hospitalized patients and is associated with extremely high mortality rates. The classical method of assessing renal function by measurement of serum creatinine is insensitive, especially in the setting of acute kidney injury (AKI) or ARF. The overall goal of these studies is to develop and validate urinary and serum biomarkers of AKI that will identify the onset and severity of kidney injury at an earlier stage than is currently possible. The availability of such biomarkers will improve the care of patients with and at risk for AKI as well as aid the development of novel therapeutic and prevention strategies. During the R21 phase, we will establish the optimal methods of collecting and processing urine and develop the analytical capability to quantitatively analyze urine for the following potential biomarkers of AKI: kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase-9 (MMP-9), glutathione-S-transferases (alpha and pi-GST), actin, interleukin-18 (IL-18), cysteine rich protein 61 (Cyr-61), and cystatin C. We will test the ability of these biomarkers to identify AKI in a cross-sectional study involving 200 patients with and without AKI. We will use statistical techniques such as multivariate receiver operating characteristic curve analysis to identify a panel of biomarkers that is sensitive and specific for the diagnosis of AKI, with an area under the receiver operating characteristics curve of at least 0.85. We will also measure urinary biomarkers from samples sent to us from six collaborating centers involved in prospective studies of AKI. On the basis of successful achievement of our aims in the R21 phase, we propose in the R33 phase a prospective study involving 400 patients undergoing coronary artery bypass graft surgery and 350 patients admitted to the medical intensive care unit. In these patients, we will test a panel of biomarkers identified during the R21 phase for their ability to identify prospectively AKI 24 hours before serum creatinine. The identification of early biomarkers of AKI will be a major step forward in the clinical care of patients at risk for AKI and will tremendously aid research on novel strategies for its prevention and treatment.