Kidney Preservation for Transplantation

描述（由申请人提供）：肾移植是确诊肾病患者最有效和最具成本效益的治疗方法。然而，缺血再灌注损伤与检索，存储和移植的肾脏从尸体是一个主要的免疫无关的因素，不利地影响早期移植功能和限制长期移植物存活。我们已经确定了Refanalin，一种有机小分子，具有显着的细胞保护活性。在缺血性、梗阻性和化学毒性肾损伤的动物模型中，Refanalin治疗可预防肾功能障碍，减少细胞凋亡和坏死细胞死亡。本提案探讨了这种小分子在肾移植背景下的治疗潜力。通过防止缺血再灌注相关的肾细胞死亡，Refanalin可以保护移植物的活力和功能，防止移植物排斥反应，降低受体死亡率。当前提案中的研究旨在为深入的临床前II期研究提供足够的支持数据，这些研究在大型肾移植动物模型中检查了Refanalin的疗效。

DESCRIPTION (provided by applicant): Renal transplantation is the most effective and cost efficient treatment for patients with established renal disease. However ischemia-reperfusion injury associated with the retrieval, storage and transplantation of kidneys from cadavers is a major immune-independent factor adversely affecting early graft function and limiting long-term graft survival. We have identified Refanalin, an organic small molecule, with significant cytoprotective activity. In animal models of ischemic, obstructive and chemotoxic renal injury, Refanalin treatment prevented kidney dysfunction and reduced apoptotic and necrotic cell death. The present proposal explores the therapeutic potential of this small molecule in the setting of renal transplantation. By preventing ischemia-reperfusion related renal cell death, Refanalin can preserve both graft viability and function, prevent graft rejection and reduce recipient mortality. The studies in the current proposal are intended to provide sufficient supporting data for in-depth, pre-clinical Phase II studies examining Refanalin efficacy in large animal models of renal transplant.