Acute Renal Injury Sequelae in NICU Graduates (ARISING)

这项建议的科学前提是，产前因素和新生儿急性肾损伤（nAKI） 在新生儿重症监护病房（NICU）毕业生中，我们 初步数据表明，高达25%的新生儿发生nAKI，其与死亡率和CKD相关。 该NIDDK多中心临床研究实施计划补助金（U34）将使我们能够实现特定的 为U 01资助的多中心前瞻性队列研究做准备的里程碑。急性肾损伤 新生儿重症监护室毕业生后遗症（ARISING）研究将前瞻性系统采集血清肌酐（SCr） 在1000例（8个GA分层中的125例）中，出生后第一周和高风险临床情景期间 入住NICU的新生儿。该项目的中心目的是弥合基本知识差距 通过提供可靠和精确的方法来诊断nAKI和早期预测CKD， NICU毕业生的生活我们提出了以下三个相互关联但独立的具体目标。 目的1：建立一种新的2期新生儿阿基定义。当代的nAKI定义尚未发展 考虑到新生儿肾脏生理学。相反，它改编自成人KDIGO阿基定义。使用 回顾性队列，我们使用最佳SCr阈值开发了一种新的nAKI定义， 不同胎龄（GA）组（≤29和>29周GA）和出生后年龄（< 7 vs> 7 d）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 阶段1 KDIGO定义 假设1b：NKC重度nAKI定义预测死亡率的特异性优于 阶段2/3 KDIGO定义 目的2：确定阿基是否与2年校正GA（cGA）时的CKD独立相关。 母亲和新生儿风险因素可能使婴儿易患nAKI和CKD。康贝特人将以 nAKI对CKD的可归因风险（估计GFR<90 ml/min/1.73m2，尿蛋白/肌酐>0.2，血液 在2年校正胎龄（cGA）时，压力>95th%tile，和/或总肾体积（TKV）<95th%tile。 我们的假设是nAKI与产前因素控制后的复合CKD相关。 目的3：确定出院前可用哪些变量预测2年cGA时的CKD。 我们将评估肾脏健康指标（TKV、BP、蛋白尿、胱抑素C、SCr和尿液肾脏生物标志物） 早产儿为38 - 1周cGA，足月儿为44 - 1周cGA。我们的假设是我们可以预测 使用以下生物学/放射学标志物，90%确定婴儿在2年cGA时将患有复合CKD： 在cGA时获得肾脏疾病。 非常需要这些问题的答案，以帮助临床医生提供适当和及时的护理， 研究人员制定了旨在改善这一弱势群体的干预措施。

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.