CALCINEURIN INHIBITOR SPARING PROTOCOL IN PEDIATRIC KIDNEY TRANSPLANTATION (CN-

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。移植后护理和免疫抑制的改善已经导致肾移植儿科受者的短期结果越来越成功。不幸的是，与免疫抑制剂相关的发病率很高，其中一些药物可能会加速慢性移植物肾病。研究者提出，TOR抑制剂西罗莫司的使用将减少活体供者移植后免疫抑制对钙调磷酸酶抑制剂的需求。如果这项初步研究成功，研究人员将扩大方案，包括尸体供体受体和方案，包括西罗莫司覆盖下的移植前供体特异性输血（DST）。这种移植前故意暴露于供体抗原可能导致供体免疫抑制甚至进一步。这项长期建议是基于临床前观察，即DST加T细胞共刺激阻断（雷帕霉素）可能导致同种异体反应性T细胞的活化诱导细胞死亡（AICD），这对移植物有害。这些方案将包括密集的免疫监测，旨在尽早发现抗供体反应。患者将接受人源化抗CD 25单克隆抗体DACLUZIMAB，在2个月内分5次给药。首次给药将在术中给药，后续给药将每两周给药一次，直至移植后8周。还将从第-1天开始给予维持免疫抑制。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Improvements in post transplant care and immunosuppression have led to increasingly successful short-term outcome in pediatric recipients of kidney transplants. Unfortunately, morbidity associated with immunosuppressive agents is substantial and some of these drugs may accelerate chronic allograft nephropathy. The investigators propose that the use of the TOR-inhibitor, sirolimus, will obviate the need for calcineurin inhibitors in post-transplant immunosuppression in recipients of living donor grafts. If this pilot study is successful, the investigators will extend the protocol to include cadaver donor recipients and to a protocol including pre-transplant donor specific transfusions (DST) under sirolimus coverage. This deliberate pre-transplant exposure to donor antigen may lead to donor-immunosuppression even further. This long-term proposal is based on preclinical observations that DST plus T-cell costimulatory blockage (rapamycin) may result in activation induced cell death (AICD) of alloreactive T cells that are harmful to the graft. These protocols will include intense immunologic monitoring which is designed to uncover anti-donor responsiveness as early as possible. Patients will receive humanized anti-CD25 monoclonal antibody DACLUZIMAB, administered in 5 doses over a 2 month period. The first dose will be administered intra-operatively and the subsequent doses will be administered every two weeks up to 8 weeks post transplantation. Maintenance immunosuppression will also be administered beginning on Day -1.