Project Grant R41DK130764

PROTECTION OF DONOR KIDNEYS WITH SYNCHRONIZATION MODULATION ELECTRIC FIELD (SMEF) - THE OBJECTIVE OF THIS PROPOSAL IS TO EXAMINE A NOVEL TECHNIQUE CALLED IMPROVED SYNCHRONIZATION MODULATION ELECTRIC FIELD (I-SMEF) IN PROTECTION OF DONOR KIDNEYS AND IMPROVEMENT OF TRANSPLANTED GRAFT FUNCTIONS. WE WILL APPLY THE I-SMEF ON DONOR KIDNEYS DURING COLD STORAGE AND EVALUATE THE TRANSPLANTED GRAFT FUNCTION FOLLOWING KIDNEY TRANSPLANTATION IN MICE. WE HAVE DEVELOPED A NOVEL TECHNIQUE, NAMED I-SMEF, WHICH COULD NOT ONLY MAINTAIN THE PUMP FUNCTIONS, BUT ALSO GENERATE ATP MOLECULES. BRIEFLY, ON THE ONE HAND, I-SMEF MAINTAINS NA/K PUMP ACTIVITY TO ACTIVELY TRANSPORT THREE NA+ OUT AND TWO K+ IONS IN BY CONSUMING ONE ATP MOLECULE, ON THE OTHER HAND, THE ELECTRIC FIELD PROVIDES ENERGY TO THE PUMP MOLECULES SO THAT THEY CAN SYNTHESIZE ONE ATP IN EACH PUMPING CYCLE. CONSEQUENTLY, THE ATP NET-CONSUMPTION FOR THE I-SMEF-CONTROLLED NA/K PUMPS IS THEORETICALLY ZERO AT ANY PUMPING RATE, IN OTHER WORDS, THE PUMP MOLECULES CAN EFFECTIVELY BUILD UP PHYSIOLOGICAL IONIC CONCENTRATION GRADIENTS IN THE SITUATIONS WITH A LIMITED OR LACK OF ATP SUPPLY, SUCH AS IN HYPOXIA. BASED ON THE STRONG PRELIMINARY FINDINGS, WE PROPOSE TO TEST THIS TECHNIQUE IN A MOUSE KIDNEY TRANSPLANTATION MODEL. WE WILL TEST OUR HYPOTHESIS THAT APPLICATION OF THE I-SMEF ON DONOR KIDNEYS DURING COLD STORAGE PROTECTS AGAINST ISCHEMIC INJURY AND IMPROVES THE TRANSPLANTED GRAFT FUNCTIONS.