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GASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Theophylline Improves Early Allograft Function in Rat Kidney Transplantation

Departments of Pharmacology and Toxicology (A.G., D.B., C.K., C.H.G., H.O.), Oral and Maxillofacial Surgery (F.P.), Pathology (M.W.), and General Surgery (M.Sc., M.Se.), University Hospital Tuebingen, Tuebingen, Germany; and Department of General and Thoracic Surgery, University Hospital Kiel, Kiel, Germany (F.F.)

Several previous studies have demonstrated a beneficial effect of the adenosine receptor (AdoR) antagonist theophylline in different forms of acute renal failure in laboratory animals and in humans. Therefore, we wanted to test whether theophylline can also improve impaired allograft function following ischemia reperfusion injury in experimental kidney transplantation (KT). Orthotopic transplantation of the left kidney was performed from Fisher 344 into Lewis rats. All transplanted rats received daily cyclosporine (5 mg/kg). The effect of theophylline treatment (10 mg/kg) on graft function was compared with appropriate controls on day 5 after KT by assessment of glomerular filtration rate (GFR) (inulin clearance). On day 5, GFR of allografts in control rats was 0.23 ± 0.05 ml/min/g kidney weight (n = 10) compared with 0.50 ± 0.09 ml/min/g in rats receiving theophylline (n = 9, p < 0.01), representing a 2-fold increase in GFR. Renal AdoR A₁ mRNA content was significantly increased in both KT groups compared with their respective control groups, whereas mRNA of AdoR A_2a, A_2b, and A₃ were found to be unchanged. Theophylline did not affect significantly interstitial infiltration of the graft by monocytes/macrophages and T-cells. Likewise, serum cytokines [interleukin (IL)-2, IL-6, IL-10, tumor necrosis factor-] and erythropoietin plasma levels were not different among the allograft groups. The present study demonstrates that theophylline remarkably improved early renal allograft function in rats undergoing KT without influencing cytokine serum patterns or tissue inflammation. Since theophylline is a commonly used medication in humans, clinical studies in patients undergoing KT are warranted.

Address correspondence to: Dr. Hartmut Osswald, Institute of Pharmacology and Toxicology, Wilhelmstrasse 56, D-72074 Tuebingen, Germany. E-mail: hartmut.osswald{at}uni-tuebingen.de

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				A. Grenz, H. Zhang, J. Weingart, S. von Wietersheim, T. Eckle, J. Schnermann, C. Kohle, D. Kloor, C. H. Gleiter, V. Vallon, et al. Lack of effect of extracellular adenosine generation and signaling on renal erythropoietin secretion during hypoxia Am J Physiol Renal Physiol, November 1, 2007; 293(5): F1501 - F1511. [Abstract] [Full Text] [PDF]