Biomarkers in Acute Kidney Injury

描述(由申请人提供)： 急性肾功能衰竭(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。传统的通过测定血清肌酐来评估肾功能的方法是不敏感的，特别是在急性肾损伤(AKI)或ARF的情况下。这些研究的总体目标是开发和验证AKI的尿液和血清生物标志物，以比目前可能的更早阶段识别肾脏损伤的开始和严重程度。这些生物标记物的出现将改善AKI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，并发展定量分析尿液中下列潜在AKI生物标志物的能力：肾损伤分子-1(KIM-1)、中性粒细胞明胶酶相关脂蛋白(NGAL)、基质金属蛋白酶-9(MMP9)、谷胱甘肽-S转移酶(α和pi-GST)、肌动蛋白、白介素18(IL-18)、富含半胱氨酸蛋白61(CyR-61)和胱抑素C。我们将在一项横断面研究中测试这些生物标志物识别AKI的能力。我们将使用多变量受试者工作特征曲线分析等统计技术来确定一组对AKI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AKI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记物。在成功实现我们在R21阶段的目标的基础上，我们在R33阶段提出了一项前瞻性研究，涉及400名接受冠状动脉旁路移植手术的患者和350名住进内科重症监护病房的患者。在这些患者中，我们将测试一组在R21期确定的生物标记物，以确定它们在血清肌酐之前24小时识别前瞻性AKI的能力。AKI早期生物标志物的识别将在AKI高危患者的临床护理方面向前迈进一大步，并将极大地帮助研究其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.