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.
