CLINICAL Purine and Cytokine Concentrations in the Renal Vein of the Allograft During Reperfusion L. Domanski, A. Pawlik, K. Safranow, K. Jakubowska, V. Dziedziejko, D. Chlubek, J. Rozanski, M. Myslak, M. Romanowski, T. Sulikowski, J. Sienko, M. Ostrowski, and K. Ciechanowski ABSTRACT The impairment of organ function derived from ischemia-reperfusion injury is still an important problem in solid organ transplantation. Cell alterations induced by ischemia prime the tissue for subsequent damage during the reperfusion phase. The aim of present study was to examine the association between changes in cytokine and purine metabolite concentrations in graft renal vein during reperfusion. The study included 17 recipients of cadaveric renal grafts: 10 men and seven women of overall mean age of 49  7 years and cold ischemia time 25  3 hour. The levels of interleukin (IL)-1, IL-2, IL-4, IL-6, IL-10, interferon (INF)-, tumor necrosis factor (TNF)-, and TNF- in renal graft vein plasma during 5 first minutes of reperfusion were quantified by flow cytometry. Increased concentrations of IL-6, TNF-, and IL-1 were observed during reperfusion. The IFN- concentrations correlated negatively with xanthine (Xan) concentrations in renal vein blood during reperfusion, whereas there was a positive correlation between IL-2 and Xan concentrations. Moreover, the concentrations of IL-6 and IL-10 correlated negatively with hypoxanthine concentrations, and the concentrations of IL-4 also correlated negatively with Xan concentrations. The results of this study indicated the enhanced release of some cytokines during kidney graft reperfusion. It occurred in association with release of purine metabolites—the markers of energy status of renal tissue. Therefore, the enhanced cytokine production during reperfusion might influence ischemia-reperfusion injury and the early graft function. I SCHEMIA-REPERFUSION INJURY is a major cause of acute renal failure with significant impact on short- and long-term graft survivals. 1 Perfusion is a process that creates the possibility of graft injury. High perfusion pres- sure or improper fluid composition may cause diffuse endothelial damage, creation of thrombi in small vessels, as well as neutrophil infiltration. Hypothermia down-regulates the metabolic processes and prevents protease-dependent cell degranulation. Negative consequences of hypothermia and ischemia include cessation of adenosine triphosphate (ATP) synthesis and Na-K-ATPase inhibition. ATP is ca- tabolized intracellularly to adenosine and then to hypoxan- thine. 2–4 Both products migrate from the cell by sophisticated membrane transport system. Xanthine (Xan) oxidoreductase in such conditions oxidates hypoxanthine to Xan and uric acid. Superoxide radicals are another product of the reaction. They are toxic for cell membranes, may cause structural From the Departments of Nephrology, Transplantology, and Internal Medicine (L.D., A.P., J.R., M.M., K.C.), Biochemistry and Medical Chemistry (K.S., K.J., V.D., D.C.), and General and Transplantation Surgery (M.R., T.S., J.S., M.O.), Pomeranian Medical University, Szczecin, Poland. This study was financed by the State Committee for Scientific Research of Poland (grant 3P05C07324p05). Address reprint requests to Dr Leszek Andrzej Domanski, Department of Nephrology, Transplantology, and Internal Med- icine, Pomeranian Medical University, Powst. Wlkp. 72, 70-111 Szczecin, Poland. E-mail: domanle@sci.pam.szczecin.pl © 2007 by Elsevier Inc. All rights reserved. 0041-1345/07/$–see front matter 360 Park Avenue South, New York, NY 10010-1710 doi:10.1016/j.transproceed.2006.11.022 Transplantation Proceedings, 39, 1319 –1322 (2007) 1319