CALCINEURIN INHIBITOR SPARING PROTOCOL IN LIVING DONOR KIDNEY TRANSPLANTATION

活体肾移植中钙调磷酸酶抑制剂保留方案

• 批准号: 7603525
• 负责人: RUTH C MCDONALD
• 金额: $ 0.02万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2007-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7603525
• 关键词: Acute; Adverse effects; Biological Assay; Biopsy; Blood; Calcineurin; Calcineurin inhibitor; Child; Chronic; Complication; Computer Retrieval of Information on Scientific Projects Database; Cosmetics; Cyclosporine; Cyclosporins; Data; Diabetes Mellitus; Funding; Gene Expression; Genomics; Grant; Half-Life; Immunologic Monitoring; Immunologics; Immunosuppression; Institution; Kidney; Kidney Transplantation; Living Donors; Medical Surveillance; Methods; Pathogenesis; Protocols documentation; Research; Research Personnel; Resources; Risk; Safety; Sirolimus; Source; Therapeutic immunosuppression; Time; Transplant Recipients; Transplantation; United States National Institutes of Health; Urine; immune function; nephrotoxicity; neurotoxicity; programs

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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 该协议将提供有关儿童钙调神经蛋白保留方案的安全性和有效性的数据。钙调蛋白抑制剂已与PTLD的发病机理有关，回避可能会减少这种严重和经常致命的并发症的风险。重要的是，环孢菌素和他的他氨基酸都会引起急性和慢性肾毒性，这可能会大大缩短整个肾脏移植的半衰期。 此外，它们还具有其他严重的副作用，特别是增强移植后糖尿病，神经毒性，尤其是在环孢菌素的情况下，化妆品变化可能会鼓励不合规。 由于使用西罗莫司（Sirolimus）进行免疫抑制与这些并发症无关，因此我们预计用该方案治疗的儿童进行移植的并发症将更少，并且可能具有更长的肾脏半衰期。 该试验的主要目的之一是开发一系列测定法，可以更好地了解接受者的免疫状态。我们计划和其他人的先前结果已经确定了监视移植活检的安全性和价值。 我们建议通过评估对受体反反应性的更敏感测定法，以扩展这些初步结果。 这将是对未服用钙调神经蛋白抑制剂的移植受体中免疫功能的首次研究。 除了免疫监测外，还将通过基因组方法分析移植时获得的方案活检，血液和尿液，并在整个第一年获得几次其他时间，以确定移植后基因表达的差异。