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

平衡液体与生理盐水减少脓毒症儿童急性和慢性肾脏疾病的效果比较

• 批准号: 10912164
• 负责人: SUSAN L. FURTH
• 金额: $ 13.45万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10912164
• 关键词: Comparative; effectiveness; balanced; fluids; versus

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.

项目摘要 急性肾损伤（阿基）是危重儿童不良结局的风险因素，包括长期的 住院、残疾和死亡。阿基对于患有败血症的儿童尤其重要，败血症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，美国有72,000多名儿童， 每年全世界的孩子。脓毒症诱导的阿基和急性肾脏疾病（AKD，持续性）儿童 持续时间<90天的肾功能不全）也可能有慢性肾病（CKD）的风险。特定风险 脓毒症儿童中阿基和CKD的因素仍然定义不清，重要的是， 确定预防脓毒症诱导的阿基、AKD和CKD的最佳疗法。晶体液体， 对于感染性休克的复苏，对肾功能具有关键的生物学作用。新的成人数据表明， 用0.9%“正常”盐水（NS）复苏比用0.9%“正常”盐水（NS）复苏更可能诱导AKI和AKD。 平衡液体（BF）。关于液体复苏对儿童肾功能影响的数据很少。在这 研究中，我们将进行一项辅助研究，以PRagMatic儿科试验的平衡与非正常生理盐水， 脓毒症（PRoMPT BOLUS）随机临床试验。这项试验是随机选择急诊室的儿童 疑似感染性休克，接受NS或BF液体复苏。审判将决定比较 不同晶体对疑似脓毒症患儿30天肾功能和死亡的影响 冲击.但是，在试验的直接随访中不会收集阿基或CKD等结局数据 参与者因此，试验完成后剩余的知识缺口是， 儿科败血症可预防阿基，并转化为CKD的减少。为了评估这些重要的肾脏 结果，我们将使用肾脏病学卓越儿科中心（PCEN）学习健康系统核心 将临床试验数据与PEDSnet（pedsnet.org）中可用的电子健康记录数据相关联， 结果分析。本研究的主要目的是：1）评估是否用BF代替复苏 NS将减少阿基并转化为试验参与者中CKD的减少，以及2）测量真实世界 在较大的PEDSnet来源人群中，晶体液选择对脓毒症诱导的阿基和CKD的影响。到 为了实现这些目标，我们将利用PEDSnet中的电子健康记录数据来测量阿基和CKD， 在7家试验中心，2，450名儿童入组了PRoMPT BOLUS研究。证明试验的普遍性 使用真实世界比较的结果，我们将确定晶体液暴露对阿基和CKD的影响 在PEDSnet中超过16，600名前往艾德治疗败血性休克的儿童的更广泛队列中， 准实验性观察研究设计。我们还将确定其他风险因素， 脓毒症儿童中的阿基到AKD到CKD。该提案符合PCEN的目标，以促进广泛的 围绕儿童肾脏疾病的病因、诊断和治疗进行合作研究， 效率和NIDDK的使命，以评估治疗，以防止肾脏疾病的发展。