Corticosteroids for Children with Febrile Urinary Tract Infections

描述(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，尿路感染会导致永久性的肾脏疤痕。在这项研究中，我们将研究两种策略来减少尿路感染儿童肾脏瘢痕的发生率。首先，我们将检查皮质类固醇在预防肾脏瘢痕形成方面的效果。由于宿主炎症反应是肾脏瘢痕形成的最后也是最重要的一步，使用抗炎皮质类固醇治疗可能是减少肾脏瘢痕形成的最佳策略。在动物研究中，皮质类固醇的使用显著降低了肾盂肾炎后疤痕的发生率。此外，在最近的一项人类研究中，在不干扰细菌根除的情况下，在尿路感染儿童中使用皮质类固醇显著减少了炎症。我们将在390名3个月至6岁的儿童中进行一项随机、双盲、安慰剂对照的多中心试验，以确定抗生素加地塞米松治疗与单用抗生素治疗对首次发热尿路感染后6个月肾疤痕发生率的疗效。其次，我们将测试是否可以使用在尿路感染诊断时收集的临床和实验室信息来识别有瘢痕形成风险的尿路感染儿童。临床医生目前没有办法准确识别有疤痕风险的儿童。因此，目前的指南建议所有尿路感染儿童接受影像检查。我们假设结合临床数据和实验室测试可以准确地将儿童分为危险类别，并提供初步数据来支持这一假设。及早识别有瘢痕形成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)限制对这一高危亚群的成像使用。因此，建议的基于生物标记物的策略有可能减少这种多发性疾病儿童的瘢痕形成和不必要的成像测试。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、血沉、白介素6、白介素8、巨噬细胞移动抑制因子、白介素12、转化生长因子21)的信息，以制定准确识别儿童瘢痕形成风险的预测规则。初步数据表明，这些标记物是重要的；然而，在具有代表性的尿路感染儿童大样本中，它们在预测肾脏瘢痕形成方面的有效性尚未得到仔细评估。

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.