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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 本方案将提供钙调磷酸酶保留方案在儿童中的安全性和有效性数据。钙调磷酸酶抑制剂与PTLD的发病机制有关，避免使用可能会降低这种严重且经常致命的并发症的风险。重要的是，环孢霉素和他可引起急性和慢性肾毒性，这可能会大大缩短整个肾移植物的半衰期。 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，以及尤其是在环孢霉素的情况下，可能鼓励不依从的美容改变。 由于使用西罗莫司进行免疫抑制与任何这些并发症无关，我们预计采用该方案治疗的儿童移植并发症较少，肾脏半衰期可能较长。 本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体的免疫状态。我们项目和其他项目的先前结果已经确立了监测移植物活检的安全性和价值。 我们建议通过评估受体抗供体反应性的更灵敏的测定来扩展这些初步结果。 这将是第一项关于未服用钙调磷酸酶抑制剂的移植受者免疫功能的研究。 除了免疫学监测外，还将通过基因组方法分析移植时以及第一年中其他几次获得的方案活检、血液和尿液，以确定移植后基因表达的差异。