Clinical evidence of the association between serum perioperative changes in xanthine metabolizing enzymes activity and early post-transplant kidney allograft function.

Abstract

Xanthine oxidoreductase (XOR) and its active forms, dehydrogenase (XD) and oxidase (XO), act as double-edged swords during ischemia-reperfusion injury. On the one hand, their action generates antioxidants, such as uric acid (UA); however, they may strongly enhance production of free radicals. In this study, we examined the association between post-transplant graft function and perioperative xanthine metabolizing enzymes (XME) activity in kidney transplant recipients divided into early (EGF), slow (SGF), and delayed graft function (DGF) groups. XME activity and UA levels were measured in blood samples collected directly before and during the first and fifth minutes of reperfusion. Results demonstrated an increase in XO and XOR activity in all groups; however, these parameters were lower in the EGF than in the DGF group (p < 0.005; p < 0.05). XD activity increased in SGF and DGF patients (p = 0.01); nevertheless, the XD/total XOR coefficient decreased only in DGF individuals (p = 0.0007). XME sensitivity, specificity, and positive and negative predictive values in discriminating SGF/DGF from EGF were 73.3% to 78%, 54% to 62.5%, 76% to 78.6%, and 56.5%, respectively. Moreover, mixed model analysis revealed that recipients classified according to results of XOR(5) and XO(5) significantly differ in 1-year post-transplant allograft function (p = 0.04 and p = 0.02, respectively), but not in the frequency of acute rejection episodes (p = 0.66 and p = 0.90, respectively). During renal transplantation, significant changes in XME occur that are associated with early post-transplant graft function and have potential value to discern between EGF and SGF/DGF.