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.

尽管免疫抑制的改善增加了短期 肾脏同种异体移植物的生存，前六个之后的损失率 在过去的三十年中，几个月的变化不大。 这 该建议的长期目标是开发营养 补充剂会减少并发症并允许长时间改善 具有最小的免疫抑制的人的持久同种异体移植生存。 这 这项研究的具体目的是执行前瞻性，随机的 接受肾脏同种异体移植的患者的临床试验以确定 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 菜籽油含有欧米茄3和欧米茄9脂肪酸，将 当有短暂的路线时，显着延长了同种异体移植生存 环孢菌素A.稳定移植后患者的一项正在进行的研究已 表明用精氨酸和低芥酸菜籽油补充饮食会 通过减少血清肌酐的降低来改善同种异体移植功能 以及肌酐清除率的改善。 这种补充也有 降低了混合淋巴细胞培养物的反应性，并引起了 细胞因子产生从Th1转移到Th2型反应。那里 给药没有明显的不利影响 精氨酸和低芥酸菜籽油的组合长达18天。 提议 研究将随机分配接受新肾脏同种异体移植的患者 研究和对照组将接受相同的化学物质 免疫抑制。 研究小组将开始饮食补充 在移植时精氨酸和低芥酸菜子油。 研究的主要终点 将包括拒绝的发生率，被拒绝的类型和严重性， 是时候第一次拒绝，肾功能，患者和移植物存活了， 心血管事件的发病率，初始发病率和长度 再住院，发病率和感染类型，发病率 慢性排斥和对血压的影响。 预计 这些主要终点中的每一个都将受到积极的影响，并且 营养免疫调节将成为 诱导固体器官长期耐受性的治疗策略 移植。