Project Grant R42DK130764

PROTECTION OF DONOR KIDNEYS WITH SYNCHRONIZATION MODULATION ELECTRIC FIELD (SMEF) - THE GOALS OF THIS PHASE II APPLICATION: 1) DETERMINE THE TRANSLATIONAL SIGNIFICANCE OF THE I-SMEF (IMPROVED SYNCHRONIZATION MODULATION ELECTRIC FIELD) IN A PRECLINICAL ANIMAL MODEL USING ADULT YORKSHIRE PIGS WITH KIDNEY AUTOTRANSPLANTATION; AND 2) DETERMINE THE OPTIMAL PARAMETERS OF THE I-SMEF IN PROTECTION AGAINST ISCHEMIC INJURY OF THE DONOR KIDNEYS DURING COLD STORAGE AND IMPROVEMENT OF THE TRANSPLANTED GRAFT FUNCTION. IN THE PHASE I PROPOSAL, WE HAVE DEVELOPED A NOVEL TECHNIQUE, NAMED I-SMEF (PATENT PENDING). THE I-SMEF NOT ONLY CONTROLS THE NA/K PUMP ACTIVITY, BUT ALSO GENERATES ATP MOLECULES. BRIEFLY, BY UTILIZING THE INTRINSIC DUAL ENERGY TRANSFORM FUNCTIONS OF THE NA/K PUMPS, WE SPECIALLY DESIGNED THE I-SMEF TO CONTROL NA/K PUMP ACTIVITY. MEANWHILE, THE ELECTRIC FIELD PROVIDES ADEQUATE ENERGY TO THE PUMP MOLECULES SO THAT THEY CAN SYNTHESIZE ONE ATP MOLECULE FOR EACH PUMPING CYCLE. CONSEQUENTLY, THE I-SMEF CAN MAINTAIN THE NA/K PUMPING ACTIVITY IN SITUATIONS WITH AN INSUFFICIENT OR LACK OF ATP SUPPLY, SUCH AS IN HYPOXIA. THEN, WE DEMONSTRATED THAT THE APPLICATION OF THE I-SMEF ON THE DONOR KIDNEYS EFFECTIVELY PROTECTED TRANSPLANTED GRAFT FUNCTIONS IN A MOUSE KIDNEY TRANSPLANTATION MODEL. THESE DATA HAVE JUST BEEN PUBLISHED IN SCIENCE TRANSLATIONAL MEDICINE. IN THIS PHASE II PROPOSAL, WE WILL EXAMINE THE TRANSLATIONAL SIGNIFICANCE OF THE I-SMEF BY USING A PRECLINICAL PORCINE MODEL IN ADULT YORKSHIRE PIGS. TO MINIMIZE THE IMMUNORESPONSE AND FOCUS ON THE ISCHEMIA REPERFUSION INJURY, WE WILL USE KIDNEY AUTOTRANSPLANTATION MODEL. THEN, WE WILL DETERMINE THE OPTIMAL PARAMETERS, INCLUDING THE NUMBERS OF ELECTRODE PAIRS, FREQUENCY, AND VOLTAGE. CONSIDERING THE HIGH SIMILARITIES IN SIZE, ANATOMY AND PHYSIOLOGY BETWEEN HUMAN AND ADULT PIG KIDNEYS, WE BELIEVE THAT THE OPTIMAL PARAMETERS OBTAINED FROM PIGS ARE READILY APPLICABLE TO HUMANS IN THE PHASE III PROPOSAL.