INFLUENCE OF IMMUNONUTRITION AND TRANSPLANT SUCCESS

免疫营养和移植成功的影响

• 批准号: 2887686
• 负责人: J. WESLEY ALEXANDER
• 金额: $ 19.73万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2887686
• 关键词: alternative medicine; arginine; blood pressure; chemoprevention; clinical research; clinical trials; cyclosporines; diet therapy; dietary supplements; hospital utilization; human subject; kidney function; kidney transplantation; nutrition; nutrition related tag; postoperative complications; transplant rejection; transplantation immunology; vegetable oils

While improvements in immunosuppression have increased the short term survival of renal allografts, the rate of loss after the first six months has changed insignificantly during the past three decades. The long-term objective of this proposal is to develop nutritional supplements that will decrease complications and allow improved long lasting allograft survival in man with minimal immunosuppression. The specific aim of this study is to perform a prospective, randomized clinical trial in patients receiving renal allografts to determine the tolerance, safety, and efficacy of a special transplant dietary supplement. Recent animal studies have shown that both arginine and canola oil, which contains both omega 3 and omega 9 fatty acids, will remarkedly prolong allograft survival when given with a short course of cyclosporine A. An ongoing study in stable posttransplant patients has shown that dietary supplementation with arginine and canola oil will improve allograft function as measured by a decrease in serum creatinine and an improvement in creatinine clearance. This supplement has also reduced responsiveness in mixed lymphocyte cultures and has caused a shift in the cytokine production from a Th1 to Th2 type response. There have been no significant adverse effects from administration of a combination of arginine and canola oil for up to 18 days. The proposed study will randomly assign patients receiving a new renal allograft into study and control groups which will receive the same chemical immunosuppression. The study group will begin dietary supplements of arginine and canola oil at transplant. Major endpoints of the study will include incidence of rejections, type and severity of rejection, time to first rejection, renal function, patient and graft survival, incidence of cardiovascular events, incidence and length of initial and rehospitalization, incidence and types of infections, incidence of chronic rejection, and effect on blood pressure. It is anticipated that each of these major endpoints will be influenced positively and that nutritional immune modulation will become an important component of therapeutic strategies to induce long-term tolerance in solid organ transplantation.

虽然免疫抑制的改善在短期内增加了 同种异体肾移植物的存活率，前六次后的丢失率 在过去的三十年里，几个月的变化微乎其微。 这 该提案的长期目标是开发营养 补充剂可减少并发症并允许长期改善 具有最小免疫抑制的人类同种异体移植物的持久存活。 这 本研究的具体目的是进行一项前瞻性、随机 在接受同种异体肾移植的患者中进行的临床试验，以确定 特殊移植饮食的耐受性、安全性和功效 补充。 最近的动物研究表明，精氨酸和 菜籽油含有欧米伽 3 和欧米伽 9 脂肪酸， 短期疗程可显着延长同种异体移植物的存活率 环孢菌素 A。一项针对稳定移植后患者正在进行的研究 研究表明，饮食中补充精氨酸和菜籽油可以 改善同种异体移植功能（通过血清肌酐降低来衡量） 以及肌酐清除率的改善。 这个补充还有 混合淋巴细胞培养物中的反应性降低，并导致 细胞因子产生从 Th1 型反应转变为 Th2 型反应。那里 没有出现明显的不良反应 精氨酸和菜籽油的组合，效果长达 18 天。 拟议的 研究将随机分配接受新同种异体肾移植的患者 研究组和对照组将接受相同的化学物质 免疫抑制。 研究小组将开始膳食补充剂 移植时使用精氨酸和菜籽油。 研究的主要终点 将包括拒绝的发生率、拒绝的类型和严重程度， 首次排斥反应时间、肾功能、患者和移植物存活率、 心血管事件的发生率、初始和持续时间的发生率和持续时间 再住院、感染的发生率和类型、发生率 慢性排斥反应以及对血压的影响。 预计 这些主要终点中的每一个都将受到积极影响，并且 营养免疫调节将成为重要组成部分 诱导实体器官长期耐受的治疗策略 移植。