Kidney Preservation for Transplantation

描述（申请人提供）：肾移植是终末期肾衰竭患者最有效和最具成本效益的治疗方法。然而，与肾脏回收、储存和移植相关的缺血再灌注损伤是影响早期移植物功能和移植物活力的主要免疫不依赖性因素。边缘供体肾脏更容易发生缺血再灌注损伤，移植常常失败。散点因子/肝细胞生长因子是一种具有显著肾保护活性的肾营养因子。然而，其临床应用受到与其管理相关的后勤困难的限制。我们已经确定了reanalin，一种有机小分子散射因子/肝细胞生长因子模拟物，具有显著的细胞保护活性。在肾缺血再灌注损伤的体内模型中，reanalin减轻了细胞死亡，改善了肾功能。在体内肾移植模型中，reanalin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期研究旨在探索reanalin在最佳、边缘和大型动物肾移植的临床相关模型中的治疗潜力。通过减轻同种异体移植物功能障碍和预防同种异体移植物衰竭，reanalin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，reanalin可以挽救被遗弃的器官，并增加供体池。

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.