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: 8039734
• 负责人: Nader Shaikh
• 金额: $ 76.33万
• 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/8039734
• 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-12; Interleukin-6; Interleukin-8; Interleukins; 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; renal scarring; tool; 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-12; Interleukin-6; Interleukin-8; Interleukins; 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; 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. PUBLIC HEALTH RELEVANCE: In this study we will examine two ways of reducing permanent renal damage from urinary tract infection in childhood. First, we will determine whether corticosteroids given at the time of infection help prevent permanent damage to the kidneys. Second, we will determine whether blood or urine tests allow physicians to predict which children are at highest risk for renal damage; intensive treatment and follow-up of these high-risk children may help reduce the incidence of renal scarring.

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。在大约15％的病例中，UTI导致永久性肾脏疤痕。在这项研究中，我们将研究两种策略，以减少UTI儿童肾脏恐惧的发生率。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脏疤痕形成的最终也是最重要的一步，因此使用抗炎皮质类固醇治疗可能是减少肾脏疤痕的最佳策略。在动物研究中，皮质类固醇的使用大幅度降低了pyelonephritic疤痕的发生率。此外，在最近的人类研究中，尿路病童中皮质类固醇的使用显着降低了炎症，而不会干扰细菌消除。我们将在390名3个月至6岁的儿童中进行随机，双盲，安慰剂对照，多中心试验，以确定抗生素和地塞米松治疗的疗效，与单独的抗生素相比，在首次兴奋的UTI之后，肾脏疤痕的发生率仅为6个月。其次，我们将测试是否可以使用UTI诊断时收集的临床和实验室信息来识别有疤痕风险的儿童。目前，临床医生无法准确识别有疤痕风险的儿童。结果，当前的指南建议所有患有UTI的儿童都接受成像测试。我们假设临床数据和实验室测试的组合可用于将儿童准确分类为风险类别，并提供初步数据以支持这一假设。早期识别有疤痕风险的儿童将允许临床医生1）更积极地跟随和治疗这些儿童，2）将成像限制在此高风险亚组中。因此，提出的基于生物标志物的策略具有减少疤痕和不必要使用这种经常发生状态的儿童的成像测试的潜力。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）和炎症反应的信息（降钙蛋白，C反应蛋白，多形性细胞计数，红细胞沉降率，红细胞沉降率，白介素6，白介素6，Interleukin 8，Interleukin 8，Interleukigage迁移，跨性别因素，跨型抑制因子，互动抑制因素12，跨性别因素互动，使抑制因子互动12，跨性别因素互动，使抑制因子相互抑制，因此发展了。确定有疤痕风险的儿童。初步数据表明这些标记很重要。但是，尚未仔细评估它们在大量的UTI儿童代表性样本中预测肾脏疤痕的效用。 公共卫生相关性：在这项研究中，我们将研究减少儿童尿路感染永久肾脏损害的两种方法。首先，我们将确定在感染时给予的皮质类固醇是否有助于防止对肾脏的永久损害。其次，我们将确定血液或尿液检查是否允许医生预测哪些儿童面临肾脏损害最高的风险；这些高危儿童的密集治疗和随访可能有助于减少肾脏疤痕的发生率。