Corticosteroids for Children with Febrile Urinary Tract Infections

皮质类固醇治疗儿童发热性尿路感染

基本信息

批准号：
8824520
负责人：
Nader Shaikh
金额：
$ 58.94万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-04-01 至 2018-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8824520
关键词：
6 year old 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 Emergency department visit End stage renal failure Enrollment Erythrocyte Sedimentation Rate Escherichia coli Fever Fingers Guidelines Health Human Hypertension Image Incidence Infection Inflammation Inflammatory Response Interleukin-12 Interleukin-6 Interleukin-8 Interleukins Kidney Laboratories Migration Inhibitory Factor Multicenter Trials 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 acute pyelonephritis antimicrobial base double-blind placebo controlled trial follow-up high risk human study neutrophil phenylpyruvate tautomerase prevent procalcitonin renal scarring tool

项目摘要

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）是幼儿中最常见的严重细菌感染。大约 15% 的病例中，尿路感染会导致永久性肾脏疤痕。在这项研究中，我们将研究两种减少尿路感染儿童肾脏损伤发生率的策略。首先，我们将检查皮质类固醇在预防肾脏疤痕方面的功效。由于宿主炎症反应是肾疤痕形成的最后也是最重要的步骤，因此使用抗炎皮质类固醇治疗可能是减少肾疤痕形成的最佳策略。在动物研究中，使用皮质类固醇可显着降低肾盂肾炎后疤痕的发生率。此外，在最近的一项人体研究中，患有尿路感染的儿童使用皮质类固醇可以显着减少炎症，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，以确定与单独使用抗生素相比，抗生素加地塞米松治疗对肾脏疤痕发生率的疗效第一次发热性尿路感染后 6 个月。其次，我们将测试是否可以使用尿路感染诊断时收集的临床和实验室信息来识别有疤痕风险的尿路感染儿童。临床医生目前无法准确识别有疤痕风险的儿童。因此，当前的指南建议所有患有尿路感染的儿童接受影像学检查。我们假设临床数据和实验室测试的结合可以用于准确地将儿童分为风险类别，并提供初步数据来支持这一假设。及早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) 将影像学的使用限制在这一高风险亚组。因此，所提出的基于生物标志物的策略有可能减少疤痕，并减少对患有这种常见病症的儿童不必要的影像学检查。我们将收集有关宿主（年龄、种族、发烧）、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），以制定预测规则，准确识别有疤痕风险的儿童。初步数据表明这些标记很重要；然而，它们在预测大量具有代表性的尿路感染儿童样本中肾脏瘢痕形成方面的效用尚未经过仔细评估。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Support for the Use of a New Cutoff to Define a Positive Urine Culture in Young Children.

支持使用新的临界值来定义幼儿尿培养阳性。

DOI：
发表时间：
2023-10-01
期刊：
影响因子：
8
作者：
Shaikh, Nader;Lee, Sojin;Krumbeck, Janina A;Kurs
通讯作者：
Kurs

Corticosteroids to prevent kidney scarring in children with a febrile urinary tract infection: a randomized trial.

皮质类固醇可预防发热性尿路感染儿童的肾脏疤痕：一项随机试验。

DOI：
发表时间：
2020
期刊：
影响因子：
0
作者：
Shaikh, Nader;Shope, Timothy R;Hoberman, Alejandro;Muniz, Gysella B;Bhatnagar, Sonika;Nowalk, Andrew;Hickey, Robert W;Michaels, Marian G;Kearney, Diana;Rockette, Howard E;Charron, Martin;Lim, Ruth;Majd, Massoud;Shalaby;Kurs
通讯作者：
Kurs

Biomarkers for febrile urinary tract infection in children.

儿童发热性尿路感染的生物标志物。