Pediatric Transplant Infections and Outcomes

描述(由申请人提供)：尽管移植急性排斥率急剧下降，但在最近几年，短期或长期移植物存活率(GS)几乎没有增加(USRDS 2003报告)。在以前的研究中，申请者已经证明了在唯一易感的儿科人群中，移植后感染(PTI；细菌和病毒病因学)和移植后淋巴增生性疾病(PTLD)的频率上升。关于PTI的趋势及其对儿童GS的影响的数据严重缺乏。在这项提案中，申请者将从超大型移植数据库(包括USRDS和UNOS)获得关于多个移植变量、移植后疗程、住院数据、机构医疗保险支付账单索赔和患者死亡的数据文件。这些数据将被分析以检验以下假设：1)与成人相比，儿童肾移植受者在6-36个月内因PTI而死亡的风险更大；2)在最近的队列中，儿童肾移植受者因PTI而住院的频率正在增加，尤其是病毒感染；3)由于病毒感染而住院的增加增加了更糟糕的死亡审查GS的风险；4)先前接受过免疫抑制的儿童在肾移植后PTI的调整后相对风险更高，从而减少了死亡审查GS；5)涉及移植肾本身的PTI(如移植物肾盂肾炎)是减少死亡审查的GS的独立危险因素；6)接受达利珠单抗或巴利昔单抗诱导治疗的儿童肾移植受者发生PTLD的相对风险更高。这些研究将为a)减少PTI和改善GS的策略的随机前瞻性临床试验奠定基础；b)调查儿童肾移植受者的原发病毒感染如何影响移植物定向免疫的机械性研究；c)开发BK病毒感染的特定ICD-9代码，以便研究其长期影响。

DESCRIPTION (provided by applicant): Although transplant acute rejection rates have declined dramatically, in the most recent years, there have been almost no incremental gains in either short-term or longer-term graft survival (GS) rates (USRDS 2003 report). The applicants, in prior studies, have documented the rise in frequency in post-transplant infections (PTI; both bacterial and viral etiology) and post transplant lymphoproliferative disease (PTLD) in the uniquely susceptible pediatric population. There is a severe paucity of data regarding PTI trends and their impact on GS in children. In this proposal, the applicants will obtain data files from extremely large transplant databases (including USRDS and UNOS) on multiple transplantation variables, post transplant course, data on hospitalization, institutional billing claims for Medicare payment and patient death. These data will be analyzed to test the hypotheses that: 1) pediatric kidney transplant recipients are at greater risk for death due to PTI in months 6-36 as compared to adults; 2) hospitalization due to PTI, especially viral, is increasing in frequency in pediatric kidney transplant recipients in more recent cohorts; 3) this increase in hospitalization due to viral infections increases the risk of worse death-censored GS; 4) children who have received prior immunosuppression have a higher adjusted relative risk for post kidney transplant PTI and thus a reduced death-censored GS; 5) PTI involving the renal allograft itself (such as transplant pyelonephritis) represent an independent risk factor for reduced death-censored GS; 6) the relative risk of developing PTLD is higher in pediatric kidney transplant recipients who received induction therapy with daclizumab or basiliximab. These studies will set the stage for a) randomized prospective clinical trials on strategies to reduce PTI and result in improved GS; b) mechanistic studies that investigate how graft-directed immunity is affected by primary viral infections in pediatric kidney transplant recipients; c) development of a specific ICD-9 code for BK virus infection that will allow studies of its long-term effects.