AKI: Biomarker Guided Therapies

AKI：生物标志物引导治疗

• 批准号: 8548119
• 负责人: STUART L GOLDSTEIN
• 金额: $ 10.11万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8548119
• 关键词: Acute; Acute Renal Failure with Renal Papillary Necrosis; Animals; Bedside Testings; Biological Markers; Caring; Child; Child Mortality; Childhood; Clinical; Creatinine; Creatinine clearance measurement; Critically ill children; Development; Diagnosis; Dialysis procedure; Fenoldopam; Gelatinase A; Genomics; Hour; Injury; Kidney; Kidney Diseases; Liquid substance; Nephrology; Operative Surgical Procedures; Outcome; Output; Patients; Plasma; Proteomics; Public Health; Recovery; Research Personnel; Risk; Serum; Technology; Urine; base; improved; multidisciplinary; novel; prevent; translational study; urinary

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.

急性肾损伤(AKI)是一种常见的临床问题，以血清突然(48小时)升高为特征 由于损伤或侮辱导致肾脏功能或结构改变而产生的肌酐(Scr)。 尽管在危重儿童的护理方面取得了重大进展，但儿童的死亡率 Aki并没有得到改善。利用基因组和蛋白质组技术，我们鉴定了与中性粒细胞明胶酶相关的 Lipocalin(NGAL)作为一种生物标志物，在发病后非常早期在肾脏中高水平产生 肾损伤。我们为这些互补性研究制定了三个目标：NGAL定向治疗 预防AKI，NGAL定向治疗，以优化对发展为AKI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慢性肾脏病的发展。因此，这项提案的具体目标 目标1.预防急性心肌梗死--这一目标将决定是否将非诺多巴应用于有患急性心肌梗死风险的儿童 AKI基于血浆NGAL护理点检测，将预防CPB后AKI的发生。阿基 将根据修改后的儿科步枪(PRIFLE)标准确定。使用pRIFLE，AKI将 定义为肌酐清除量较术前基线水平或尿量减少：：25% 术后48小时内输出量0.5ml/kg/小时，连续6小时。目标2.预防AKI的急性并发症--该目标 将确定持续升高的NGAL是否可以预测哪些危重儿童最终会发展成 显著(&gt；10%)ICU液体积聚超过24小时，从而优化透析 入会仪式。目标3：预测AKI的长期后果-该目标将评估尿蛋白组学特征 发现新的生物标志物来预测AKI的恢复和/或AKI向CKD的转变。这个 多学科调查团队，包括儿科肾科医生、重症医生、心脏病专家和 生物统计学家将广泛使用蛋白质组学核心(核心B)和生物标记物核心(核心C)来 这一项目的圆满完成。