Acute Renal Injury Sequelae in NICU Graduates (ARISING)

NICU 毕业生的急性肾损伤后遗症 (ARISING)

• 批准号: 9899244
• 负责人: Namasivayam Ambalavanan
• 金额: $ 35.71万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9899244
• 关键词: Acute; Acute Renal Failure with Renal Papillary Necrosis; Adult; Age; Biological; Biological Markers; Birth; Blood Pressure; Caring; Cessation of life; Chronic Kidney Failure; Clinical Research; Cohort Studies; Creatinine; Data; Development; Diagnosis; Diastolic blood pressure; Disease Marker; Disease Progression; Economic Burden; Epidemiology; Event; Fetal Growth Retardation; Fibrinogen; Frequencies; Funding; Gestational Age; Glomerular Filtration Rate; Grant; Health; Hospitalization; Hospitals; Human; Incidence; Infant; Injury to Kidney; Intervention Studies; Kidney; Kidney Diseases; Knowledge; Life; Measurement; Measures; Methods; Mind; Multi-site clinical study; National Institute of Diabetes and Digestive and Kidney Diseases; Neonatal; Neonatal Intensive Care Units; Outcome; Physiology; Pre-Eclampsia; Premature Infant; Preparation; Prospective Studies; Prospective cohort; Prospective cohort study; Proteins; Proteinuria; Radiology Specialty; Research Design; Research Personnel; Retrospective cohort; Risk; Risk Factors; Sensitivity and Specificity; Serum; Site; Specificity; Time; Urine; Variant; Vulnerable Populations; age group; base; clinical risk; evidence base; high risk; high risk infant; improved outcome; in utero; mortality; neonate; novel; outcome prediction; post gamma-globulins; postnatal; pre-clinical; prenatal; prenatal risk factor; primary outcome; prospective; therapy design

The scientific premise for this proposal is that prenatal factors and neonatal acute kidney injury (nAKI) significantly contribute to chronic kidney disease (CKD) in neonatal intensive care unit (NICU) graduates. Our preliminary data suggests that up to 25% of neonates develop nAKI, which is associated with mortality and CKD. This NIDDK Multi-Center Clinical Study Implementation Planning Grant (U34) will enable us to achieve specific milestones in preparation for a U01-funded, multi-center, prospective cohort study. The Acute Renal Injury Sequela In NICU Graduates (ARISING) study will prospectively capture serum creatinine (SCr) systematically during the first postnatal week and during high-risk clinical scenarios in 1000 (125 across 8 GA strata) neonates admitted to the NICU. The project's central purpose is to bridge fundamental knowledge gaps in the field by providing reliable and precise methods to diagnose nAKI and predict CKD early in the life of NICU graduates. We propose the following 3 inter-related but independent specific aims. Aim 1: Validate a novel 2-stage neonatal AKI definition. The contemporary nAKI definition was not developed with neonatal kidney physiology in mind. Instead, it was adapted from the adult KDIGO AKI definition. Using a retrospective cohort, we developed a novel nAKI definition using the optimal SCr thresholds which predict mortality for different gestational age (GA) groups (≤29 and >29 week GA), and postnatal age (< 7 vs  7 days) Hypothesis 1a: The NKC mild nAKI definition will have greater sensitivity to predict mortality than the stage 1 KDIGO definition Hypothesis 1b: The NKC severe nAKI definition will have better specificity to predict mortality than the stage 2/3 KDIGO definition Aim 2: Determine if AKI is independently associated with CKD at 2 years corrected GA (cGA). Maternal and neonatal risk factors may predispose infants to both nAKI and CKD. We will determine the attributable risk of nAKI on CKD (estimated GFR<90 ml/min/1.73m2, urine protein/creatinine >0.2, blood pressure >95th%tile, and/or total kidney volume (TKV) <95th%tile at 2 years corrected gestational age (cGA). Our hypothesis is that nAKI is associated with a composite CKD after controlling for prenatal factors. Aim 3: Determine which variable(s) available prior to hospital discharge predict CKD at 2 years cGA. We will evaluate metrics of kidney health (TKV, BP, proteinuria, cystatin C, SCr and urine kidney biomarkers) at 38  1 week cGA for preterm and 44  1 weeks cGA for term infants. Our hypothesis is that we can predict with 90% certainty which infants will have composite CKD at 2 years cGA using biological/radiologic markers of kidney disease obtained at term cGA. Answers to these questions are greatly needed to help clinicians provide appropriate and timely care, and help researchers develop interventions designed to improve outcomes in this vulnerable population.

该提案的科学前提是产前因素和新生儿急性肾损伤（nAKI） 新生儿重症监护病房（NICU）毕业生中慢性肾脏病（CKD）的发病率显着升高。 初步数据表明，高达 25% 的新生儿患有 nAKI，这与死亡率和 CKD 相关。 NIDDK 多中心临床研究实施规划拨款 (U34) 将使我们能够实现特定目标 U01 资助的多中心前瞻性队列研究的里程碑。 新生儿重症监护病房毕业生 (ARISING) 的 Sequela 研究将前瞻性地系统地捕获血清肌酐 (SCr) 产后第一周和 1000 次高风险临床场景（8 个 GA 层中的 125 次） 该项目的中心目的是弥合基础知识差距。 通过提供可靠且精确的方法来诊断 nAKI 并在早期预测 CKD 我们提出以下 3 个相互关联但独立的具体目标。 目标 1：验证新的 2 阶段新生儿 AKI 定义 当代 nAKI 定义尚未制定。 相反，它是根据成人 KDIGO AKI 定义改编的。 回顾性队列研究中，我们使用最佳 SCr 阈值开发了一种新的 nAKI 定义，该阈值预测 不同胎龄 (GA) 组（≤29 周和 >29 周 GA）和产后年龄（< 7 与 ≥ 7 天）的死亡率 假设 1a：NKC 轻度 nAKI 定义对预测死亡率的敏感性高于 第一阶段 KDIGO 定义 假设 1b：NKC 严重 nAKI 定义比 NKC 严重 nAKI 定义在预测死亡率方面具有更好的特异性。 阶段 2/3 KDIGO 定义 目标 2：确定 2 年校正 GA (cGA) 时 AKI 是否与 CKD 独立相关。 孕产妇和新生儿危险因素可能使婴儿易患 nAKI 和 CKD。 CKD 发生 nAKI 的归因风险（估计 GFR<90 ml/min/1.73m2、尿蛋白/肌酐 >0.2、血液 2 岁校正胎龄 (cGA) 时压力 >95%tile，和/或肾总体积 (TKV) <95th%tile。 我们的假设是，在控制产前因素后，nAKI 与复合 CKD 相关。 目标 3：确定出院前可用的哪些变量可以预测 2 年 cGA 时的 CKD。 我们将评估肾脏健康指标（TKV、血压、蛋白尿、胱抑素 C、SCr 和尿肾生物标志物） 早产儿的 cGA 为 38 ± 1 周，足月儿的 cGA 为 44 ± 1 周。我们的假设是，我们可以预测。 使用生物/放射学标记，90% 确定哪些婴儿在 2 年 cGA 时将患有复合 CKD cGA 足月时患有肾脏疾病。 非常需要这些问题的答案，以帮助提供适当和及时的护理，并帮助 研究人员制定了旨在改善这一弱势群体的结果的干预措施。