Pediatric Transplant Infections and Outcomes

描述（由申请人提供）：尽管移植急性排异率急剧下降，但近年来，短期或长期移植存活率（GS）几乎没有增加（USRDS 2003报告）。在先前的研究中，申请人已经记录了移植后感染（PTI；细菌和病毒病因）和移植后淋巴细胞增生性疾病（PTLD）在独特易感儿科人群中的频率上升。关于PTI趋势及其对儿童GS的影响的数据严重缺乏。在本提案中，申请人将从超大型移植数据库（包括USRDS和UNOS）中获取有关多个移植变量、移植后过程、住院数据、医疗保险支付机构账单索赔和患者死亡的数据文件。将对这些数据进行分析，以验证以下假设：1)与成人相比，儿童肾移植受者在6-36个月内因PTI死亡的风险更高；2)在最近的队列中，儿童肾移植受者因PTI（尤其是病毒性PTI）住院的频率正在增加；3)由于病毒感染而住院的增加增加了更严重的死亡审查GS的风险；4)既往接受过免疫抑制的儿童在肾移植后发生PTI的调整相对风险较高，因此死亡审查GS降低；5)涉及同种异体肾移植本身的PTI（如移植肾盂肾炎）是减少死亡审查GS的独立危险因素；6)接受daclizumab或basiliximab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并改善GS的随机前瞻性临床试验奠定基础；B)研究移植物定向免疫如何受到儿童肾移植受者原发性病毒感染影响的机制研究；c)制定BK病毒感染的特定ICD-9代码，以便对其长期影响进行研究。

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.