Comparative effectiveness of balanced fluids versus normal saline to reduce acute and chronic kidney disease in children with sepsis

项目总结 急性肾损伤(AKI)是危重儿童不良结局的危险因素，包括延长 住院、残疾和死亡。Aki对于患有脓毒症的儿童尤其重要，这是一种医疗紧急情况 由于感染导致的危及生命的器官功能障碍，影响到美国超过7.2万名儿童和400万名儿童 世界各地的儿童每年都会受到影响。脓毒症所致AKI和急性肾脏疾病(AKD，持续性)的儿童 持续90天的肾功能障碍)也可能导致慢性肾脏疾病(CKD)。特定风险 脓毒症儿童中AKI和CKD的因素仍然不明确，重要的是，仍存在差距 确定预防脓毒症引起的AKI、AKD和CKD的最佳治疗方法。晶态流体，这是 对于感染性休克的复苏，对肾功能有重要的生物学作用。在成年人中出现的数据表明 与用0.9%生理盐水(NS)复苏相比，用0.9%生理盐水(NS)复苏更有可能诱发AKI和AKD 平衡液(BF)。有关液体复苏对儿童肾功能影响的数据很少。在这 研究，我们将进行一项辅助研究，以实用的儿科试验的平衡与生理盐水 脓毒症(速效推注)随机临床试验。这项试验是对急诊科的儿童进行随机抽样 疑似感染性休克，用生理盐水或BF进行液体复苏。审判将确定比较 不同晶体对疑似脓毒症患儿30天内肾功能和死亡的影响 令人震惊。然而，关于AKI或CKD等结果的数据将不会在试验的直接后续行动中收集 参与者。因此，试验完成后剩下的一个知识缺口将是高炉复苏是否在 儿童败血症可预防AKI，并转化为慢性肾脏病的减少。评估这些重要的肾脏 结果，我们将使用儿科肾病卓越中心(PCEN)学习健康系统核心 将临床试验数据链接到PEDSnet(ededsnet.org)上提供的电子健康记录数据，以增强试验 结果分析。这项研究的主要目标是：1)评估是否使用BF进行复苏 NS将降低AKI，并转化为试验参与者CKD的减少，以及2)测量真实世界 在更大的PEDSnet来源人群中，晶体流体选择对脓毒症诱导的AKI和CKD的影响。至 为了实现这些目标，我们将利用PEDSnet的电子健康记录数据来衡量AKI和CKD 2450名儿童在7个试验点参加了速效丸剂研究。论证试验的概括性 结果通过真实世界的比较，我们将确定晶体流体暴露对AKI和CKD的影响 在PEDS net的一个更广泛的队列中，超过16,600名儿童向急诊室提出使用 准实验观察性研究设计。我们还将确定进展的其他风险因素 脓毒症患儿由AKI到AKD再到CKD。这项提议与PCEN的目标一致，以促进广泛的 围绕增多症儿童肾脏疾病的病因、诊断和治疗的合作研究 效率和NIDDK的使命是评估预防肾脏疾病发展的治疗方法。

PROJECT SUMMARY Acute kidney injury (AKI) is a risk factor for adverse outcomes in critically ill children, including prolonged hospitalization, disability, and death. AKI is particularly significant for children with sepsis, a medical emergency due to life-threatening organ dysfunction from infection that affects over 72,000 children in the US and four million children worldwide each year. Children with sepsis-induced AKI and acute kidney disease (AKD, persistent kidney dysfunction of <90 days duration) may also be at risk for chronic kidney disease (CKD). Specific risk factors for AKI and CKD among children with sepsis remain poorly defined and, importantly, gaps remain in identifying the best therapies to prevent sepsis-induced AKI, AKD, and CKD. Crystalloid fluid, the cornerstone of resuscitation for septic shock, has key biological effects on kidney function. Emerging data in adults suggest that resuscitation with 0.9% “normal” saline (NS) is more likely to induceAKI and AKD compared to resuscitation with balanced fluids (BF). Few data on the impact of fluid resuscitation on kidney function in children exist. In this study, we will perform an ancillary study to the PRagMatic Pediatric Trial of Balanced vs. nOrmaL saline flUid in Sepsis (PRoMPT BOLUS) randomized clinical trial. That trial is randomizing children in emergency departments with suspected septic shock to fluid resuscitation with either NS or BF. The trial will determine the comparative effectiveness of different crystalloids on 30-day kidney function and death in children with suspected septic shock. However, data on outcomes such as AKI or CKD will not be collected in direct follow-up of trial participants. A remaining knowledge gap after trial completion will therefore be whether BF resuscitation in pediatric sepsis protects against AKI and translates to a decrease in CKD. To assess these important kidney outcomes, we will use the Pediatric Center of Excellence in Nephrology (PCEN) Learning Health System Core to link clinical trial data to electronic health record data available in PEDSnet (pedsnet.org) to augment trial outcome analyses. The primary objectives of this study are to: 1) assess whether resuscitation with BF instead of NS will decrease AKI and translate to a decrease in CKD in trial participants, and 2) measure the real-world impact of crystalloid fluid choice on sepsis-induced AKI and CKD in the larger PEDSnet source population. To achieve these objectives, we will utilize electronic health record data in PEDSnet to measure AKI and CKD in 2,450 children enrolled in the PRoMPT BOLUS study at 7 trial sites. To demonstrate generalizability of trial results using a real-world comparison, we will determine the impact of crystalloid fluid exposure on AKI and CKD in a broader cohort of over 16,600 children in PEDSnet presenting to an ED for treatment of septic shock using a quasi-experimental observational study design. We will also determine other risk factors for progression from AKI to AKD to CKD in children with sepsis. This proposal aligns with the PCEN goal to facilitate extensive collaborative research around the causes, diagnosis, and treatment of kidney diseases in children with increased efficiency and NIDDK’s mission to evaluate treatments to prevent the development of kidney disease.