Risk factors for renal scarring in children after urinary tract infection

描述（由申请人提供）： 尿路感染（UTI）是儿童期最常见的严重细菌感染，约占6岁儿童的3%。目前对患有UTI的幼儿的护理标准是进行排尿性膀胱尿道造影（VCUG），以评估膀胱输尿管反流（VUR）的存在，这是一种在约30-40%的UTI儿童中发现的疾病，被认为会增加肾瘢痕形成和肾功能不全的风险。UTI后发现有VUR的儿童每天接受预防性抗生素治疗，直到VUR消退或手术矫正VUR。近年来，我们对UTI、VUR和肾瘢痕形成的关系的理解，以及目前管理儿童UTI的策略受到了挑战。现在清楚的是，肾瘢痕形成可发生在没有VUR的儿童中，并且即使是高度VUR的大多数儿童也不会发生肾瘢痕形成，这表明VUR以外的因素决定了肾瘢痕形成的发展。2005年秋季，NIDDK开始资助RIVUR（膀胱输尿管反流随机干预; U 01-DK 074064），这是一项为期5年的多中心随机对照试验，旨在评价预防性抗菌剂预防初次UTI和VCUG上存在VUR的儿童复发性UTI和肾瘢痕形成的有效性和危害。参与RIVUR的三家临床试验中心将在UTI诊断时招募患者，并对他们进行VUR筛查。而不是完全排除那些没有VUR的人，我们建议将他们纳入一项辅助观察性研究，以更全面地了解使儿童处于肾瘢痕形成风险的因素，无论他/她是否有VUR。我们的具体目的是（1）比较辅助研究中未发生VUR的儿童和RIVUR研究中发生VUR并接受安慰剂的儿童中自索引UTI 2年后发生肾瘢痕的儿童比例，以及（2）开发一种预测规则，准确地识别一组儿童在发展肾瘢痕的高风险，以及一组儿童几乎了解哪些儿童在泌尿道感染后肾瘢痕形成的风险最大，将允许临床医生提供更多的针对性治疗和干预措施，以防止这种不良后果。

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.