Kidney Preservation for Transplantation

移植时的肾脏保存

• 批准号: 7053153
• 负责人: PRAKASH NARAYAN
• 金额: $ 91.36万
• 依托单位: ANGION BIOMEDICA CORPORATION
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7053153
• 关键词: age difference; analog; animal tissue; apoptosis; dogs; dosage; dosage forms; drug screening /evaluation; hepatocyte growth factor; high throughput technology; histocompatibility; homologous transplantation; kidney transplantation; laboratory rat; necrosis; pharmacokinetics; postoperative complications; renal ischemia /hypoxia; reperfusion; small molecule; transplant rejection; transplantation immunology

DESCRIPTION (provided by applicant): Renal transplantation is the most effective and cost-efficient treatment for patients in end-stage kidney failure. However ischemia-reperfusion injury, associated with the retrieval, storage and transplantation of kidneys is a major immune-independent factor adversely affecting early graft function and graft viability. Marginal donors kidneys, are even more susceptible to ischemia-reperfusion injury, and often fail transplantation. Scatter factor/hepatocyte growth factor is a renal trophic factor with significant renooprotective activity. However its clinical use is limited by the logistical difficulties associated with its administration. We have identified Refanalin, an organic small molecule scatter factor/hepatocyte growth factor mimetic, with significant cytoprotective activity. In in vivo models of renal ischemia-reperfusion injury, Refanalin attenuated cell death and improved renal function. In an in vivo model of renal transplantation, Refanalin treatment attenuated mortality, improved graft function and preserved graft viability. The present Phase II proposal explores the therapeutic potential of Refanalin in clinically relevant models of optimal, marginal and large animal renal transplantation. By attenuating allograft dysfunction and preventing allograft failure, Refanalin can reduce recipient morbidity and mortality. By attenuating ischemia-reperfusion injury in the marginal kidney, Refanalin can salvage an otherwise discarded organ, and increase the donor pool.

描述（申请人提供）：肾移植是终末期肾衰竭患者最有效且最具成本效益的治疗方法。然而，与肾脏的取出、保存和移植相关的缺血再灌注损伤是一个主要的免疫独立因素，对早期移植物功能和移植物活力产生不利影响。边缘供体的肾脏更容易受到缺血再灌注损伤，并且常常会失败。分散因子/肝细胞生长因子是一种具有显着肾脏保护活性的肾脏营养因子。然而，其临床应用受到与其给药相关的后勤困难的限制。我们已经鉴定出Refanalin，一种有机小分子分散因子/肝细胞生长因子模拟物，具有显着的细胞保护活性。在肾缺血再灌注损伤的体内模型中，Refanalin 减少了细胞死亡并改善了肾功能。在肾移植体内模型中，Refanalin 治疗降低了死亡率，改善了移植物功能并保留了移植物活力。目前的 II 期提案探讨了 Refanalin 在最佳、边缘和大型动物肾移植临床相关模型中的治疗潜力。通过减轻同种异体移植功能障碍并预防同种异体移植失败，Refanalin 可以降低受体的发病率和死亡率。通过减轻边缘肾的缺血再灌注损伤，Refanalin 可以挽救原本被丢弃的器官，并增加供体库。