Defining the Impact of Obesity on Pediatric Urinary Tract Infections

项目摘要 泌尿道感染（UTI）是儿童最常见的细菌感染之一， 发病率和死亡率。确定的风险因素并不能解释所有儿童UTI。最近的证据表明 肥胖可能在UTI易感性中起重要作用，但肥胖与儿童UTI之间的关系 未定义。在儿童中，几项已发表的将肥胖与UTI风险增加联系起来的研究是基于小的 研究规模仅限于幼儿、住院儿童或在肥胖率较低的国家进行 比大多数西方国家。因此，全面评价儿童肥胖对UTI的影响， 在门诊和医院环境中的易感性、频率和严重性是有保证的。此外，机械 需要研究来确定肥胖如何改变UTI风险。我们团队的初步数据表明， 通过抑制宿主UTI防御增加UTI风险-包括产生细胞因子，抗菌素 肽（AMP），并破坏膀胱的尿路上皮屏障。因此，该应用程序旨在解决 肥胖对UTI风险、复发和复发的重要影响被低估， 严重性通过削弱先天宿主UTI防御。为了解决这个假设，我设计了这个应用程序， 以下目的：（目的1）确定肥胖对儿童UTI频率和严重程度的影响。我会 访问大型儿科责任护理组织数据库，以确定UTI的发病率，复发率和短期- 和长期发病率。(Aim 2）询问肥胖对泌尿系统的影响 道的先天宿主UTI防御。我会用一个已建立的生物储存库来定量尿液中的AMP， 细胞因子和尿斑蛋白屏障蛋白。这些研究的完成将确定肥胖作为UTI风险的作用 儿童因素，以及建立肥胖增加UTI易感性的机制。这项工作 对儿童UTI管理、预防和治疗策略的重要见解具有重要的前景。 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 开展以儿科UTI为重点的有影响力的成果转化研究。 .

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. .