AKI: Biomarker Guided Therapies

急性肾损伤（阿基）是一种常见的临床问题，其定义为血清肌酐（BUN）突然（约48小时）升高， 肌酸酐（SCr）是由损伤或损害引起的，导致肾脏功能或结构变化。 尽管在重症儿童的护理方面取得了重大进展， 阿基没有改善。利用基因组学和蛋白质组学技术，我们鉴定了中性粒细胞明胶酶相关的 脂质运载蛋白（NGAL）作为一种生物标志物，在肾脏中产生高水平， 肾损伤我们为这些补充研究制定了三个目标：NGAL定向治疗， 预防阿基，NGAL定向治疗，以优化对发生阿基和生物标志物的患者的支持/ 蛋白质组学分析以早期预测或检测CKD发展。因此，本建议的具体目标 目标：1。预防阿基-这一目标将决定是否给予有AKI风险的儿童非诺多泮， 基于血浆NGAL床旁检测的阿基将预防CPB后阿基的发生。阿基 将根据改良的儿科步枪（pRIFLE）标准确定。使用PRIFLE，阿基将 定义为估计的肌酐清除率较术前基线水平或尿肌酐水平降低<25% 手术后48小时内6小时输出量< 0.5 ml/kg/hr。目标2.预防阿基的急性并发症-这一目标 将确定持续升高的NGAL是否可以预测哪些重症儿童最终会发展为 显著（>10%）阳性ICU液体累积超过24小时，从而优化透析 入会仪式目的3：预测阿基的长期后果-该目的将评估尿蛋白质组学特征， 发现新的生物标志物以预测阿基恢复和/或阿基向CKD的转变。的 多学科研究团队，包括儿科肾病学家、重症监护医生、心脏病学家和 生物统计学家将广泛使用蛋白质组学核心（核心B）和生物标志物核心（核心C）， 这个项目的顺利完成。

Acute Kidney Injury (AKI) is a common clinical problem defined by an abrupt (¿ 48 hour) increase in serum creatinine (SCr) resulting from an injury or insult causing a functional or structural change in the kidney. Despite significant advancements in the care of the critically ill child, mortality rates in children who develop AKI have not improved. Using genomic and proteomic technologies, we identified neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker that is produced in high levels in the kidney very early after kidney injury. We have developed three aims for these complementary studies: NGAL directed therapy to prevent AKI, NGAL directed therapy to optimize support for patients who develop AKI and biomarker/ proteomic profiling to predict or detect CKD development early. Accordingly the specific aims of this proposal are: Aim 1. Prevent AKI - this aim will determine if the administration of fenoldopam to children at risk for AKI, based upon plasma NGAL point of care testing, will prevent the occurrence of AKI following CPB. AKI will be determined based on the modified pediatric RIFLE (pRIFLE) criteria. Using pRIFLE, AKI will be defined as an estimated creatinine clearance decrease by <:: 25% from preoperative baseline level or urine output < 0.5 ml/kg/hr for 6 hours within 48h of surgery. Aim 2. Prevent acute complications of AKI - this aim will determine if persistently elevated NGAL can predict which critically ill children will ultimately develop significant (>10%) positive ICU fluid accumulation for more than 24 hours and thereby optimize dialysis initiation. Aim 3: Predict long term consequences of AKI - this aim will assess urinary proteomic profiles for discovery of novel biomarkers to predict the AKI recovery and/or transition of AKI to CKD. The multidisciplinary team of investigators, including pediatric nephrologists, intensivists, cardiologists, and biostatisticians will extensively employ the Proteomics Core (Core B) and the Biomarker Core (Core C) for the successful completion of this project.