Corticosteroids for Children with Febrile Urinary Tract Infections

皮质类固醇治疗儿童发热性尿路感染

• 批准号: 8636457
• 负责人: Nader Shaikh
• 金额: $ 58.58万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8636457
• 关键词: 6 year old; Accident and Emergency department; Accounting; Acute; Adjuvant; Adjuvant Therapy; Admission activity; Adrenal Cortex Hormones; Age; Alleles; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Antibiotic Therapy; Antibiotics; Bacteria; Bacterial Infections; Biological Markers; Bladder; Blood; C-reactive protein; Categories; Cell Count; Child; Childhood; Cicatrix; Clinical; Clinical Data; DMSA; Data; Demographic Factors; Dexamethasone; Diagnosis; Double-Blind Method; Early identification; Early treatment; End stage renal failure; Enrollment; Erythrocyte Sedimentation Rate; Escherichia coli; Fever; Fingers; Guidelines; Human; Hypertension; Image; Incidence; Infection; Inflammation; Inflammatory Response; Interleukin-1; Interleukin-12; Interleukin-6; Interleukin-8; Kidney; Laboratories; Migration Inhibitory Factor; Office Visits; Physicians; Placebo Control; Placebos; Pre-Eclampsia; Race; Randomized; Research Personnel; Risk; Sampling; Scanning; Secondary to; Specimen; Staging; Subgroup; Testing; Time; Transforming Growth Factors; Urinary tract infection; Urine; Vesico-Ureteral Reflux; Visit; acute pyelonephritis; antimicrobial; base; double-blind placebo controlled trial; follow-up; high risk; human study; neutrophil; phenylpyruvate tautomerase; prevent; procalcitonin; public health relevance; renal scarring; tool

DESCRIPTION (provided by applicant): Urinary tract infection (UTI) is the most common serious bacterial infection in young children. In approximately 15% of cases, UTI leads to permanent renal scarring. In this study, we will examine two strategies to reduce the incidence of renal scaring in children with UTI. First, we will examine the efficacy of corticosteroids in preventing renal scarring. Because host inflammatory response is the final and most important step in the formation of renal scars, the use of anti-inflammatory corticosteroid therapy may be the best strategy to reduce renal scarring. In animal studies, the use of corticosteroids dramatically reduces the incidence of post-pyelonephritic scarring. In addition, in a recent human study, the use of corticosteroids in children with UTI significantly reduced inflammation without interfering with bacterial eradication. We will conduct a randomized, double-blind, placebo-controlled, multi- center trial in 390 children 3 months to 6 years of age, to determine the efficacy of antibiotics plus dexamethasone therapy, compared with antibiotics alone, on the incidence of renal scarring 6 months after a first febrile UTI. Second, we will test whether children with UTI who are at risk for scarring can be identified using clinical and laboratory information collected at the time of UTI diagnosis. Clinicians currently have no means of accurately identifying children at risk for scarring. As a result, current guidelines recommend that all children with UTI undergo imaging tests. We hypothesize that a combination of clinical data and laboratory tests can be used to accurately stratify children into risk categories, and present preliminary data to support this hypothesis. Early identification of children at risk for scarring will allow clinicians to 1) follow and treat these children more aggressively, and 2) limit use of imaging to this high-risk subgroup. Thus, the proposed biomarker-based strategy has the potential to reduce both scarring and the unnecessary use of imaging tests for children with this frequently occurring condition. We will collect information about the host (age, race, fever), the bacteria (E. coli papGIA2 allele) and the inflammatory response (procalcitonin, C-reactive protein, polymorphonuclear cell count, erythrocyte sedimentation rate, interleukin 6, interleukin 8, macrophage migration inhibitory factor, interleukin 12, transforming growth factor 21) to develop a prediction rule that accurately identifies children at risk for scarring. Preliminary data suggest that these markers are important; however, their utility in predicting renal scarring in a large representative sample of children with UTI has not been carefully evaluated.

描述（由申请人提供）：尿路感染（UTI）是幼儿最常见的严重细菌感染。在大约15%的病例中，尿路感染导致永久性肾瘢痕。在这项研究中，我们将探讨两种策略来减少尿路感染儿童肾脏惊吓的发生率。首先，我们将检查皮质类固醇在预防肾瘢痕形成方面的功效。由于宿主炎症反应是肾瘢痕形成的最后和最重要的步骤，使用抗炎皮质类固醇治疗可能是减少肾瘢痕形成的最佳策略。在动物实验中，皮质类固醇的使用显著降低了肾盂肾炎后瘢痕的发生率。此外，在最近的一项人体研究中，在患有UTI的儿童中使用皮质类固醇可以显著减少炎症，而不会干扰细菌的根除。我们将对390名3个月至6岁的儿童进行一项随机、双盲、安慰剂对照、多中心试验，以确定抗生素加地塞米松治疗与单独使用抗生素相比，对首次发热性尿路感染后6个月肾瘢痕发生率的影响。其次，我们将测试是否可以使用在UTI诊断时收集的临床和实验室信息来识别有疤痕风险的UTI儿童。临床医生目前还没有办法准确地识别有疤痕风险的儿童。因此，目前的指南建议所有患有尿路感染的儿童接受影像学检查。我们假设结合临床数据和实验室测试可以准确地将儿童划分为风险类别，并提供初步数据来支持这一假设。早期识别有疤痕风险的儿童将使临床医生能够1)更积极地跟踪和治疗这些儿童，2)限制对这一高风险亚组的影像学使用。因此，提出的基于生物标志物的策略有可能减少这种经常发生的疾病的儿童的疤痕和不必要的影像学检查。我们将收集有关宿主（年龄、种族、发热）、细菌（大肠杆菌papGIA2等位基因）和炎症反应（降钙素原、c反应蛋白、多形核细胞计数、红细胞沉降率、白细胞介素6、白细胞介素8、巨噬细胞迁移抑制因子、白细胞介素12、转化生长因子21）的信息，以制定准确识别儿童疤痕风险的预测规则。初步数据表明这些标记很重要；然而，它们在预测尿路感染儿童的大量代表性样本中的肾瘢痕形成方面的效用尚未得到仔细评估。