Nephroprotective effect of pentoxifylline in renal ischemia-reperfusion in rat depends on the timing of its administration.
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 (ClCr; mL/min/kg body weight), fractional excretions of sodium (FENa [%]) and potassium (FEK [%]), and urine protein/ClCr ratio (Uprot/ClCr [mg/1 mL ClCr]) 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: ClCr 2.10 ± 0.44 versus 1.03 ± 0.18; FENa 0.16 ± 0.12 versus 0.84 ± 0.55; FEK 40.3 ± 13.0 versus 75.5 ± 17.9, respectively (all P < .001). There was no difference in proteinuria: Uprot/ClCr 0.004 ± 0.002 versus 0.004 ± 0.002. Conversely, the analyzed parameters did not differ between animals administered PTX during IRI and controls: ClCr 0.42 ± 0.34 versus 0.73 ± 0.43; FENa 2.98 ± 2.71 versus 3.16 ± 3.05; FEK 280.1 ± 155.7 versus 206.2 ± 154.1; and Uprot/ClCr 0.031 ± 0.029 versus 0.029 ± 0.031, respectively, nor between rats given PTX after IRI and controls: ClCr 0.29 ± 0.38 versus 0.40 ± 0.47; FENa 4.25 ± 3.55 versus 3.80 ± 3.94; FEK 284.9 ± 117.5 versus 243.0 ± 150.6; and Uprot/ClCr 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.
Department of General, Vascular and Transplant Surgery, Medical University of Silesia, Katowice, Poland.
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Wystrychowski
Department of Internal Medicine, Diabetology, and Nephrology, Medical University of Silesia, Katowice, Poland. Electronic address: wystrych@gmail.com.
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Wystrychowski
Department of Internal Medicine, Diabetology, and Nephrology, Medical University of Silesia, Katowice, Poland.
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Zukowska-Szczechowska
Department of Pharmacology, Medical University of Silesia, Katowice, Poland.
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Obuchowicz
Department of Internal Medicine, Diabetology, and Nephrology, Medical University of Silesia, Katowice, Poland.
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Grzeszczak
Department of Nephrology, Endocrinology and Metabolic Diseases, Medical University of Silesia, Katowice, Poland.
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Więcek
Department of Nephrology, Endocrinology and Metabolic Diseases, Medical University of Silesia, Katowice, Poland.
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Wystrychowski
D058186:Acute Kidney Injury / Q000517:prevention & control*; D000818:Animals; D003250:Constriction; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007249:Inflammation; D007668:Kidney / Q000187:drug effects*; D016030:Kidney Transplantation; D008297:Male; D009392:Nephrectomy; D010431:Pentoxifylline / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*
D016166:Free Radical Scavengers; D010431:Pentoxifylline