This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.This protocol will provide data on the safety and efficacy of the calcineurin sparing protocol in children. The calcineurin inhibitors have been implicated in the pathogenesis of PTLD and the avoidance may lessen the risk of this serious and frequently fatal complication. Importantly, both cyclosporine and tacroliums cause acute and chronic nephrotoxicity which may shorten overall kidney graft half-lives substantially. Furthermore they also have other serious side effects, specifically the enhancement of post transplant diabetes, neurotoxicity and, especially in the case of cyclosporine, cosmetic changes which may encourage non-compliance. Since the use of Sirolimus for immunosuppression has not associated with any of these complications, we expect that transplantation in children treated with this protocol will have fewer complications and may have longer kidney half-lives.One of the major aims of this trial is to develop a battery of assays that can be utilized to provide a better understanding of the immunologic status of the recipient. Previous results for our program and others have established the safety and value of surveillance graft biopsies. We propose to extend these preliminary results by evaluating even more sensitive assays of recipient anti-donor reactivity. This will be the first study of immune function in transplant recipients not taking calcineurin inhibitors. In addition to immunologic monitoring, the protocol biopsies, blood and urine obtained at the time of transplant and several additional times throughout the first year will be analyzed by genomic methods to determine differences in gene expression post transplantation.
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