Biphasic behavior of the kinetics of 31P-containing metabolites in ischemic porcine kidneys

The assessment of kidney viability before transplantation (with a view of discarding nonviable organs) remains an obstacle to confidently extending organ harvesting to marginal donors. In the present study phosphorus magnetic resonance spectroscopy was used to monitor metabolic changes in 31P-containing metabolites in isolated porcine kidneys. After various warm ischemia times, the organs were stored at 0°C. Time-dependent changes in the phosphomonoester/inorganic-phosphate ratio were recorded at 0°C were shown to follow a biexponential decay. The first-order kinetic rate constant of the short-time decay was strongly dependent on the warm ischemia time, a result that was discreted in terms of the underlying biochemistry. The metabolic events responsible for the dramatic decrease in phosphomonoester/inorganic phosphate ratio that occur immediately after organ perfusion and storage, suggest that any procedure to minimize organ damage must occur immediately after harvesting. Many reports have dealt with the application of magnetic resonance spectroscopy (MRS) and imaging (MRI) to kidney studies in vitro or in vivo. Most of these studies have provided physiologic and biochemical information on kidney metabolism, but an increasing number of investigations have aimed to monitor renal function in disease.1 A particular field of application for MRS in renal studies concerns monitoring of organs for transplantation. [2], [3] and [4] In fact, quantitative organ viability parameters are difficult to obtain using conventional techniques, whereas 31P MRS provides an elegant, noninvasive image of the organ's energy status. [5] and [6] These investigations have assessed kidney viability before transplantation with a view to discarding nonviable organs, or monitored metabolic modifications during organ storage to understand the biochemical processes behind transplant failure and thereby optimize the storage conditions. Moreover, it has recently been suggested that 31P metabolites be measured in the early, period after renal transplantation to diagnose primary and early allograft dysfunction.4 Both animal and human studies have reported the use of 31P MRS to assess renal viability, specific metabolic parameters have been correlated with organ quality vis-a-vis transplantation. In particular, the recovery of renal function has been shown to be inversely related to the depletion of high-energy metabolites. [7] and [8] Because ATP or ADP peaks almost disappear during storage, the ratio between the phosphomonoesters and the inorganic phosphate ([PME]/[Pi]) has been proposed as a reliable viability parameter. [9] and [10] It has been monitored under various storage conditions in several animal models or in cadaveric human organs. However, these studies obtained semiempirical parameters as prognostic indices of renal recovery after transplantation, but provided little information on the biochemical events responsible for renal injury. Moeller et al [11] and [12] reported time-dependent changes in pH and metabolite concentrations during hypothermic storage of cadaveric kidneys. They described a model of ischemic phosphate turnover using human kidneys beginning almost 3 hours after organ excision; all information concerning shorter storage times was lost. However, the processes occurring just after excision must have a great influence on organ viability, because a rapid [PME]/[Pi] decay was observed after nephrectomy.6 As a consequence, understanding the metabolic events after excision should improve organ preservation and clinical outcomes of organ transplantation. Herein we present a study on the kinetics of metabolic changes induced by cold and warm ischemia in pig kidneys monitored from about 20 minutes after organ explanation. The remarkable early metabolic events and quantitative kinetic data are assessed.