Protection of donor kidney and transplanted graft function by modulating Na/K ATPase activity

Kidney transplantation is a life-saving procedure for patients with end-stage kidney disease, however, organ shortage is a global crisis. We have developed a novel technique, named improved Synchronization Modulation Electric Field (i-SMEF). The i-SMEF not only controls the Na/K pump activity, but also generates ATP molecules. In a recent publication, we demonstrated that application of the i-SMEF on donor kidneys effectively protected transplanted graft functions in a mouse kidney transplantation model. However, it is unknown if the i-SMEF could repair the injured cells during ischemia, thereby exhibiting more protective effects on marginal organs. In the present proposal, we will examine the role of the i-SMEF in a protection against ischemic injury in cultured cells, isolated kidneys, and kidney transplantation models in rats and pigs. We propose to test our hypothesis that the i-SMEF rescues and repairs the injured cells in marginal organs during storage and exhibits more protective effects than in standard criteria donor kidneys via delaying ATP depletion, preserving mitochondrial function, preventing Na/K pump translocation, and reducing the inflammatory response. We believe that the novel concept that the i-SMEF controls renal Na/K pump activities and repairs injured kidney cells during storage would update and advance our understanding of the regulation and significance of the renal Na/K pump activity in ischemia. Its applications in kidney transplantation are expected to have imminent translational significance in expanding the donor pool and improving the long-term survival of transplanted grafts. Moreover, the i-SMEF is expected to exhibit important protective effects against acute kidney injury in vascular and kidney surgeries that may compromise renal blood supply.