Magnetic resonance study of renal transplantation

In the last few years, we have focused our research effort on the magnetic resonance spectroscopic (NMR) studies of organ transplantation in the rat. P-31 NMR was employed to study changes in high-energy phosphates, intracellular pH in vivo of transplanted kidneys either during normal function, while undergoing the rejection process or subjected to other insults (e.g. ischemia, cyclosporine nephrotoxicity, urinary obstruction) which may also cause graft dysfunction. Nuclear magnetic resonance (NMR) parameters, specifically relative peak areas and intracellular pH, accurately distinguished among the different causes of graft dysfunction. Ureteral obstruction was clearly identified by elevations in the phosphodiester/urine phosphate peak. Ischemia and rejection were both associated with increases in inorganic phosphates and phosphomonesters and decreases in the beta-phosphate peak of adenosine triphosphate but were distinguishable from each other by differences in intracellular pH which was normal in rejected allografts (7.33 +/- 0.07, n = 3) and low in ischemic allografts (7.00 +/- 0.05, n = 3, p less than 0.05). Grafts insulted with cyclosporine toxicity were not distinguishable from normal allografts by any of the parameters studied. To determine the temporal relationship of NMR changes in allograft rejection, similar studies were performed serially in a group of rejecting (R) kidneys (n = 7) and compared with a control group of nonrejecting (NR) kidneys (n = 7). Major decrease in adenosine triphosphate (ATP) with increases in Pi and a marked increase in the Pi/ATP ratio were noted in the R allografts over time. The R allografts could be completely segregated from the NR allografts on the basis of the Pi/ATP ratio by day 7. These data suggest that 31P NMR spectroscopy may have potential clinical application in differentiating among the causes of graft failure of human renal allografts.