Risk factors for renal scarring in children after urinary tract infection

描述(由申请人提供)： 项目摘要/摘要尿路感染(UTI)是儿童中最常见的严重细菌感染，到6岁时约有3%的儿童受到影响。目前对患有尿路感染的幼儿的护理标准是进行排尿膀胱尿路造影(VCUG)以评估是否存在膀胱输尿管反流(VUR)，这种情况在大约30%-40%的尿路感染儿童中发现，被认为会增加肾脏瘢痕形成和肾功能不全的风险。在尿路感染后被发现患有VUR的儿童每天接受预防性抗生素治疗，直到VUR消失，或者接受手术矫正VUR。近年来，我们对尿路感染、输尿管返流和肾脏瘢痕形成的关系的理解，以及目前治疗尿路感染儿童的策略都受到了挑战。现在明确的是，肾疤痕可以发生在没有VUR的儿童身上，而大多数即使是高级别VUR的儿童也不会发展成肾脏疤痕，这表明除了VUR之外的其他因素决定了肾脏疤痕的发展。2005年秋天，NIDDK开始资助RIVUR(膀胱输尿管返流的随机干预；U01-DK074064)，这是一项为期5年的多中心随机对照试验，旨在评估预防性抗菌药在预防初发尿路感染和VCUG上存在VUR的儿童中预防复发尿路感染和肾脏疤痕的有效性和危害。参与RIVUR的三个临床试验中心将在UTI诊断时招募患者，并将对他们进行VUR筛查。与其完全排除那些没有VUR的人，我们建议将他们纳入一项辅助观察性研究，以更全面地了解导致儿童发展为肾脏疤痕的风险的因素，无论他/她是否有VUR。我们的具体目标是(1)比较辅助研究中没有VUR并正在接受安慰剂治疗的辅助研究中没有VUR的儿童和RIVUR研究中确实有VUR并正在接受安慰剂治疗的儿童中，从UTI指数开始两年内发生肾疤痕的儿童的比例，以及(2)开发一种预测规则，该规则可以准确地识别一组发生肾疤痕的高危儿童以及一组几乎没有发生UTI后发生肾疤痕的风险的儿童。PROJECT叙述性了解哪些儿童在UTI后肾疤痕形成的风险最大，将使临床医生能够提供更有针对性的治疗和干预措施，以防止这种不利结果。

DESCRIPTION (provided by applicant): PROJECT SUMMARY/ABSTRACT Urinary tract infection (UTI) is the most common serious bacterial infection in childhood, affecting approximately 3% of all children by six years of age. The current standard of care for young children who present with UTI is to perform a voiding cystourethrogram (VCUG) to evaluate for the presence of vesicoureteral reflux (VUR), a condition found in approximately 30-40% of children with UTI that is thought to increase the risk of renal scarring and renal insufficiency. Children found to have VUR after a UTI are treated with daily prophylactic antibiotics until the VUR resolves, or have surgical correction of the VUR. In recent years, our understanding of the relationship of UTI, VUR, and renal scarring, and current strategies for managing children with UTI have been challenged. It is now clear that renal scarring can occur in children who do not have VUR, and that most children with even high grade VUR do not develop renal scarring, suggesting that factors other than VUR determine the development of renal scarring. In the fall of 2005, the NIDDK began funding RIVUR (Randomized Intervention for Vesicoureteral Reflux; U01-DK074064), a 5-year multicenter randomized controlled trial designed to evaluate the effectiveness and harms of prophylactic antimicrobials for the prevention of recurrent UTIs and renal scarring in children with an initial UTI and presence of VUR on a VCUG. Three of the clinical trial centers participating in RIVUR will be recruiting patients at the time of UTI diagnosis and will be screening them for presence of VUR. Rather than completely dismissing those who do not have VUR, we propose to enroll them in an ancillary observational study to understand more fully the factors that place a child at risk of developing renal scarring, regardless of whether he/she has VUR. Our specific aims are (1) to compare the proportion of children who develop renal scarring 2 years from the index UTI among children in the ancillary study who do not have VUR and those in the RIVUR study who do have VUR and are receiving placebo, and (2) to develop a prediction rule that accurately identifies a group of children at high risk of developing renal scarring as well as a group of children with virtually no risk of developing renal scarring after the index UTI.PROJECT NARRATIVE Understanding which children are at the greatest risk of renal scarring after a UTI will allow clinicians to provide more targeted therapies and interventions to prevent this adverse outcome.