Nephroprotective Effect of Pentoxifylline in Renal IschemiaeReperfusion in Rat Depends on the Timing of Its Administration W. Wystrychowski a , G. Wystrychowski b, *, E. _ Zukowska-Szczechowska b , E. Obuchowicz c , W. Grzeszczak b , A. Więcek d , and A. Wystrychowski d a Department of General, Vascular and Transplant Surgery, b Department of Internal Medicine, Diabetology, and Nephrology, c Department of Pharmacology, and d Department of Nephrology, Endocrinology and Metabolic Diseases; Medical University of Silesia, Katowice, Poland ABSTRACT Background. Renal ischemiaereperfusion injury (IRI) induces inflammatory reaction damaging kidney. Pentoxifylline (PTX) given before IRI attenuates inflammation and prevents ischemic acute kidney injury (iAKI). Given that in clinical settings IRI is not always predictable, we aimed to assess whether PTX administration during or shortly after IRI affects the course of iAKI in the rat. Methods. In 58 male 10-week-old Sprague-Dawley rats, 14 days after right nephrectomy, a 45-minute clamping of solitary renal pedicle was conducted. PTX 100 mg/kg body weight or 0.9% NaCl 1 mL were given subcutaneously either 60 minutes before renal ischemia, 1 minute into ischemia, or 60 minutes after clamp release. Creatinine clearance (Cl Cr ; mL/ min/kg body weight), fractional excretions of sodium (FE Na [%]) and potassium (FE K [%]), and urine protein/Cl Cr ratio (U prot /Cl Cr [mg/1 mL Cl Cr ]) at 48 hours after IRI were compared between PTX-treated animals and respective controls (Mann-Whitney U test). Results. Kidney function was improved in rats given PTX before IRI compared with con- trols: Cl Cr 2.10  0.44 versus 1.03  0.18; FE Na 0.16  0.12 versus 0.84  0.55; FE K 40.3  13.0 versus 75.5  17.9, respectively (all P < .001). There was no difference in proteinuria: U prot / Cl Cr 0.004  0.002 versus 0.004  0.002. Conversely, the analyzed parameters did not differ between animals administered PTX during IRI and controls: Cl Cr 0.42  0.34 versus 0.73  0.43; FE Na 2.98  2.71 versus 3.16  3.05; FE K 280.1  155.7 versus 206.2  154.1; and U prot / Cl Cr 0.031  0.029 versus 0.029  0.031, respectively, nor between rats given PTX after IRI and controls: Cl Cr 0.29  0.38 versus 0.40  0.47; FE Na 4.25  3.55 versus 3.80  3.94; FE K 284.9  117.5 versus 243.0  150.6; and U prot /Cl Cr 0.044  0.018 versus 0.055  0.061, respectively. Conclusions. PTX given only before, and not at the time of renal ischemia or after reperfusion, alleviates subsequent iAKI in the rat. This implicates usefulness of PTX in the clinical settings of expected renal ischemia, like kidney transplantation, and suggests po- tential benefits of PTX in peritransplant period foremost with donor pretreatment. R ENAL ISCHEMIAeREPERFUSION INJURY (IRI) causes glomerular capillary endothelial dysfunction and tubular epithelial necrosis leading to ischemic acute kidney injury (iAKI) with activation of inflammatory reaction medi- ated by increased cytokine and adhesion molecule expression, macrophage recruitment as well as reactive oxygen species synthesis and neutrophil activation [1]. As a consequence, progressive glomerular sclerosis, tubular atrophy, and chronic kidney failure may develop [2]. Recent observations indicate *Address correspondence to Grzegorz Wystrychowski, MD, PhD, Department of Internal Medicine, Diabetology and Nephrology, Medical University of Silesia, ul. 3 Maja 13-15, 41-800 Zabrze, Poland. E-mail: wystrych@gmail.com ª 2014 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710 0041-1345/14 http://dx.doi.org/10.1016/j.transproceed.2014.09.052 Transplantation Proceedings, 46, 2555e2557 (2014) 2555