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. ? ?
| Tian, Tao; Lindell, Susanne L; Henderson, Scott C et al. (2009) Protective effects of ezrin on cold storage preservation injury in the pig kidney proximal tubular epithelial cell line (LLC-PK1). Transplantation 87:1488-96 |
