Nephroprotective Effect of Pentoxifylline in Renal Ischemia–Reperfusion in Rat Depends on the Timing of Its Administration

Abstract Background Renal ischemia–reperfusion 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 controls: 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 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 potential benefits of PTX in peritransplant period foremost with donor pretreatment.