Defining the Impact of Obesity on Pediatric Urinary Tract Infections

项目总结 尿路感染(UTI)是儿童最常见的细菌感染之一，其结果显著 发病率和死亡率。已确定的危险因素并不能解释所有的儿科尿路感染。最近的证据表明 肥胖可能在尿路感染易感性中起重要作用，但肥胖与儿童尿路感染的关系 未定义。在儿童中，几项发表的将肥胖与尿路感染风险增加联系起来的研究是基于 研究规模，仅限于幼儿、住院儿童，或在肥胖程度较低的国家进行 比大多数西方国家都要高。因此，全面评估儿童肥胖对尿路感染的影响 在门诊和医院环境中的敏感性、频率和严重性是有保证的。此外，机械论 需要研究来定义肥胖如何改变尿路感染风险。我们团队的初步数据表明，肥胖 通过抑制宿主UTI防御--包括细胞因子、抗菌剂的产生--增加UTI风险 多肽(AMP)和破坏膀胱的尿路上皮屏障。因此，此应用程序旨在解决 关于肥胖对尿路感染风险、复发和 通过削弱固有的宿主UTI防御系统而造成的严重后果。为了解决这个假设，我设计了这个应用程序来满足 以下目标：(目标1)确定肥胖对儿童尿路感染的频率和严重程度的影响。这就做 访问大型儿科责任护理组织数据库，以确定尿路感染的发生率、复发和短期- 以及所有患者护理环境中的长期发病率。(目标2)询问肥胖对尿路的影响 TRAIL的天然宿主UTI防御系统。我将使用已建立的生物资料库来量化尿AMP，促炎症 细胞因子和一种尿路蛋白屏障蛋白。这些研究的完成将把肥胖定义为泌尿系感染的风险 肥胖是儿童的致病因素，并建立肥胖增加尿路感染易感性的机制。这部作品 对儿童尿路感染的管理、预防和治疗策略的重要洞察具有重要的前景。 它还为我提供了一个特殊的培训机会，以发展所需的分析和实验室技能 为了进行有影响力的、以结果为基础的转化性研究，重点是儿科尿路感染。 。

PROJECT SUMMARY Urinary tract infection (UTI) is one of the most common bacterial infections in children and results in significant morbidity and mortality. Established risk factors do not account for all pediatric UTI. Recent evidence suggests obesity may play an important role in UTI susceptibility, but the relationship between obesity and pediatric UTI is not defined. In children, several published studies linking obesity to increased UTI risk are based on small study sizes, limited to young children, hospitalized children, or were performed in countries with lower obesity rates than most Western countries. Thus, a comprehensive evaluation of the effects of childhood obesity on UTI susceptibility, frequency, and severity in ambulatory and hospital settings is warranted. In addition, mechanistic studies are needed to define how obesity alters UTI risk. Preliminary data from our team suggest that obesity increases UTI risk by suppressing host UTI defenses – including the production of cytokines, antimicrobial peptides (AMP), and disrupting the bladder’s urothelial barrier. As a result, this application is designed to address the central hypothesis that obesity has an underappreciated and significant impact on UTI risk, recurrence, and severity by weakening innate host UTI defenses. To address this hypothesis, I designed this application to meet the following objectives: (Aim 1) Define the effect of obesity on the frequency and severity of pediatric UTI. I will access a large pediatric accountable care organization database to define UTI incidence, recurrence, and short- and long- term morbidity across all patient care settings. (Aim 2) Interrogate the impact of obesity on the urinary tract’s innate host UTI defenses. I will use an established biorepository to quantify urinary AMPs, proinflammatory cytokines, and a uroplakin barrier protein. Completion of these studies will define the role of obesity as a UTI risk factor in children, as well as establish mechanisms through which obesity increases UTI susceptibility. This work holds significant promise for crucial insight into pediatric UTI management, prevention, and treatment strategies. It also provides me with an exceptional training opportunity to develop the analytic and laboratory skills required to perform impactful outcomes-based translational research focused on pediatric UTI. .