422.3: Using a New Preservation Solution Called Perla for Kidney Transplantation

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Background: The composition of organ preservation solutions is crucial for maintaining graft integrity and is directly related to morbidity and survival after transplantation. The aim of this study is to compare the function of rat kidney grafts after organ storage in the new organ preservation solution PERLA® (patented by Barcelona University; PCT/ES2009/000267) and the gold standard solution of University of Wisconsin (UW). On the one hand, UW contains HES (inducing erythrocyte aggregation), high-K+ concentration (causing hyperkalemic cardiac arrest) and some drugs like allopurinol, GSH or adenosine which does not confer any protection. Oh the other hand, PERLA® solution is a high Na+/low K+ liquid including PEG-35 (1 g/L), trimetazidine (1 µM), carvedilol (10 μM) and tacrolimus (5 μM). These last three compounds have been reported as strong modulators of ischemia-reperfusion (I/R) injury. Methods: To assess oxidative stress after cold storage, kidney grafts have been preserved for 18 h at 4° C in either UW or PERLA® solutions and then oxidative stress markers were determined in renal tissues. To evaluate kidney injuries and oxidative stress after graft reperfusion, rat kidneys were harvested, stored in cold UW or in PERLA® solutions for 18 h and then transplanted heterotopically for 6 h. In order to determine the potential benefits of PERLA® solution, antioxidant enzymes (superoxide dismutase–SOD; glutathione peroxidase-GPX; reduced glutathione-GSH; catalase-CAT) activities and oxidative stress parameters (malondialdehyde-MDA; conjugated dienes-CD- formation and protein sulfhydryl-PSH were determined in renal tissue. In addition, cytolysis (measuring lactate dehydrogenase-LDH levels in plasma) and kidney function (quantifying plasma concentrations of uric acid and creatinine) were determined. Results: Kidney transplantation using UW solution led to a significant increase in the oxidative stress and renal lesions parameters and, in parallel, to a decrease in the activities of all the antioxidant enzymes. Our results showed that preservation of kidneys in PERLA® solution significantly attenuates oxidative stress parameters after cold storage and reperfusion. Indeed, we found a significant decrease in oxidative damage indicator (MDA, CD and CP) and a significant increase in antioxidant indicators (GPx, GSH, CAT, SOD and PSH). Moreover, PERLA® solution decreases kidney injury after reperfusion (Creatinine, LDH and uric acid). Conclusion: Our study shows that PERLA solution was more effective in preserving rat’s kidney grafts than the gold standard UW solution. PERLA preservation solution was able to reduce oxidative stress and to improve the functional recovery of kidney grafts during cold ischemia and after trasnplantation.

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