CALCINEURIN INHIBITOR SPARING PROTOCOL IN LIVING DONOR KIDNEY TRANSPLANTATION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 该方案将提供有关儿童钙调神经磷酸酶备用方案的安全性和有效性的数据。钙调神经磷酸酶抑制剂与PTLD的发病机制有关，避免使用钙调神经磷酸酶抑制剂可能会降低这一严重且经常致命的并发症的风险。重要的是，环孢素和他克利都会引起急性和慢性肾毒性，这可能会大大缩短整个移植肾的半衰期。此外，它们还有其他严重的副作用，特别是增加移植后糖尿病、神经毒性，特别是在环孢素的情况下，美容改变可能会鼓励不遵守规定。由于西罗莫司用于免疫抑制与这些并发症中的任何一个都没有关联，我们预计使用该方案治疗的儿童移植的并发症将较少，并可能有更长的肾脏半衰期。 这项试验的主要目的之一是开发一系列检测方法，可用于更好地了解受试者的免疫状态。我们和其他项目以前的结果已经确定了监测移植物活组织检查的安全性和价值。我们建议通过评估更敏感的受体抗供体反应性试验来扩展这些初步结果。这将是第一次对不服用钙调神经磷酸酶抑制剂的移植受者的免疫功能进行研究。除了免疫学监测，还将通过基因组方法分析移植时和第一年内多次获得的方案活检、血液和尿液，以确定移植后基因表达的差异。

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. 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.