NONINVASIVE MONITORING OF KIDNEYS AWAITING TRANSPLANT

THE LONG-TERM GOSL OF THIS RESEARCH IS TO CONSTRUCT AND EVALUATE A NONINVASIVE DEVICE THAT WILL ASSESS THE FUNCTIONAL INTEGRITY OF HYPOTHERMIC PERFUSED KIDNEYS PRIOR TO TRANSPLANT. THE DEVICE IS BASED ON MEASUREMENTS OF CHANGES IN MITOCHONDRIAL ELECTRON-TRANSPORT PROTEIN-OXIDATION STATES IN THE KIDNEY CORTEX. THESE CHANGES CAN BE MEASURED SPECTROPHOTOMETRICALLY AND WILL BE IMAGED AT THE SURFACE OF THE HYPOTHERMIC PERFUSED KIDNEY WITH THE DEVICE TO BE DEVELOPED IN THIS PROPOSAL. IN PHASE I, RAT KIDNEYS WILL BE PERFUSED UNDER HYPOTERMIC CONDITIONS AND REFLECTANCE SPECTRA OF THE KIDNEY CORTEX RECORDED AT INCREMENTAL PERFUSION PRESSURES. SIMILAR SPECTRA WILL ALSO BE RECORDED FOR CHEMICALLY UNCOUPLED KIDNEYS AND FOR KIDNEYS THAT HAVE BEEN SUBJECTED TO WARM ISCHEMIA. REDUCTION IN CYTOCHROMES C AND AA3 WILL BE CORRELATED WITH RENAL PERFUSION FLOW, OXYGEN CONSUMPTION, AND PHYSIOLOGIC MEASURES OF RENAL FUNCTION. AN IMAGING REFLECTANCE SPECTROMETER WILL BE CONSTRUCTED. USING WAVELENGTHS AND CONDITIONS ESTABLISHED IN THE SCANNING STUDIES, MONOCHROMATIC IMAGES OF THE KIDNEY CORTEX WILL BE COLLECTED AND PROCESSED TO PRODUCE A FALSE COLOR IMAGE OF THE KIDNEY THAT DEPICTS AREAS OF MITOCHONDRIAL UNCOUPLING AND ISCHEMIA. PHASE II STUDIES WILL ESTABLISH CORRELATIONS BETWEEN THE CORTICAL MITOCHONDRIA FUNCTIONAL STATE UNDER HYPOTHERMIC PERFUSION AND TIME FOR RECOVERY OF RENAL FUNCTION FOLLOWING TRANSPLANT AND VIABILITY OF THE TRANSPLANTED KIDNEY.