AKI: Biomarker Guided Therapies

AKI：生物标志物引导治疗

• 批准号: 8731223
• 负责人: STUART L GOLDSTEIN
• 金额: $ 10.33万
• 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/8731223
• 关键词: Acute; Acute Renal Failure with Renal Papillary Necrosis; Adult; Adverse effects; Agreement; American; Animals; Area; Bedside Testings; Biological Markers; Caring; Cells; Child; Child Mortality; Childhood; Chronic; Clinical; Comorbidity; Creatinine; Creatinine clearance measurement; Critical Illness; Critically ill children; Data; Development; Diabetes Mellitus; Diagnosis; Dialysis procedure; Disease; Dose; Double-Blind Method; Early Diagnosis; Early Intervention; Enrollment; Excision; Exhibits; Fenoldopam; Fluid overload; Functional disorder; Gelatinase A; Gene Expression; Genomics; Heart Diseases; Hour; Human; Incidence; Industry; Injury; Kidney; Kidney Diseases; Licensing; Liquid substance; Lung diseases; Measurement; Mechanical ventilation; Nephrology; Operative Surgical Procedures; Organ failure; Outcome; Output; Patients; Pharmaceutical Preparations; Plasma; Proteins; Proteome; Proteomics; Public Health; Randomized; Recovery; Research Personnel; Risk; Serum; Severity of illness; Societies; Technology; Therapy Clinical Trials; Triage; United States National Institutes of Health; Urine; base; cohort; effective therapy; high risk; improved; multidisciplinary; novel; patient population; point of care; prevent; prospective; 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（阿基）是一种常见的临床问题，其定义为由损伤或损害引起的血清肌酐（SCr）的突然（< 48小时）增加，所述损伤或损害引起肾脏的功能或结构变化。尽管重症儿童的护理取得了重大进展，但发生阿基的儿童的死亡率并未改善。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脂质运载蛋白（NGAL）作为一种生物标志物，其在肾损伤后非常早期在肾脏中以高水平产生。我们为这些互补研究制定了三个目标：NGAL定向治疗以预防阿基，NGAL定向治疗以优化对发生阿基的患者的支持，以及生物标志物/蛋白质组学分析以早期预测或检测CKD的发展。因此，本提案的具体目标是：目标1。预防阿基-这一目标将根据血浆NGAL床旁检测确定对有阿基风险的儿童给予非诺多泮是否会预防CPB后阿基的发生。将根据改良的儿科步枪（pRIFLE）标准确定阿基。使用pRIFLE，阿基将定义为估计肌酐清除率较术前基线水平降低≥ 25%或手术48小时内持续6小时尿量< 0.5 ml/kg/hr。目标二。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患儿最终会出现显著（>10%）的ICU液体积聚阳性超过24小时，从而优化透析启动。目标三：预测阿基的长期后果-该目标将评估尿蛋白质组学谱，以发现新的生物标志物，从而预测阿基恢复和/或阿基向CKD的转变。多学科研究者团队，包括儿科肾病专家、重症监护专家、心脏病专家和生物统计学家，将广泛采用蛋白质组学核心（核心B）和生物标志物核心（核心C），以成功完成本项目。