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Int. J. Mol. Sci. 2018, 19(1), 221; doi:10.3390/ijms19010221

Pentoxifylline and Methylprednisolone Additively Alleviate Kidney Failure and Prolong Survival of Rats after Renal Warm Ischemia-Reperfusion

1
Department of Internal Medicine, Diabetology and Nephrology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia in Katowice, 41-800 Zabrze, Poland
2
Department of General, Vascular and Transplant Surgery, School of Medicine in Katowice, Medical University of Silesia in Katowice, 40-027 Katowice, Poland
3
Department of Nephrology, Transplantation and Internal Medicine, School of Medicine in Katowice, Medical University of Silesia in Katowice, 40-027 Katowice, Poland
*
Author to whom correspondence should be addressed.
Received: 30 November 2017 / Revised: 27 December 2017 / Accepted: 7 January 2018 / Published: 11 January 2018
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Abstract

Renal ischemia-reperfusion injury (IRI) induces local inflammation leading to kidney damage. Since pentoxifylline (PTX) and steroids have distinct immunomodulatory properties, we aimed to evaluate for the first time their combined use in IRI-induced acute kidney injury (AKI) and chronic kidney disease (CKD) in rats. In two experiments, PTX (100 mg/kg body weight subcutaneously) was administered 90 min prior to renal IRI or/and methylprednisolone (MP; 100 mg/kg body weight intramuscularly) was infused 60 min after reperfusion of a solitary kidney (AKI model: 45 min ischemia, 48 male Sprague-Dawley rats) or one kidney with excision of contralateral kidney 2 weeks later (CKD model: 90 min ischemia, 38 rats). Saline was infused in place of PTX or/and MP depending on the group. Renal function (diuresis, serum creatinine, creatinine clearance, sodium and potassium excretion, and urine protein/creatinine) was assessed at 48 h and 120 h post-IRI (AKI model) or 4, 16 and 24 weeks after IRI, along with survival analysis (CKD model). More evidently at early stages of AKI or CKD, treated animals showed higher glomerular filtration and diminished tubular loss of electrolytes, more so with PTX + MP than PTX or MP (serum creatinine (μmol/L) at 48 h of AKI: 60.9 ± 19.1 vs. 131.1 ± 94.4 vs. 233.4 ± 137.0, respectively, vs. 451.5 ± 114.4 in controls, all p < 0.05; and at 4 weeks of CKD: 89.0 ± 31.9 vs. 118.1 ± 64.5 vs. 156.9 ± 72.6, respectively, vs. 222.9 ± 91.4 in controls, p < 0.05 for PTX or PTX + MP vs. controls and PTX + MP vs. MP). Survival was better by >2-fold with PTX + MP (89%) vs. controls (40%; p < 0.05). PTX + MP largely protect from IRI-induced AKI and CKD and subsequent mortality in rats. This calls for clinical investigations, especially in kidney transplantation. View Full-Text
Keywords: ischemia; reperfusion; ischemia-reperfusion injury; acute kidney injury; chronic kidney disease; pentoxifylline; steroid; survival; mortality; kidney transplantation ischemia; reperfusion; ischemia-reperfusion injury; acute kidney injury; chronic kidney disease; pentoxifylline; steroid; survival; mortality; kidney transplantation
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Wystrychowski, G.; Wystrychowski, W.; Grzeszczak, W.; Więcek, A.; Król, R.; Wystrychowski, A. Pentoxifylline and Methylprednisolone Additively Alleviate Kidney Failure and Prolong Survival of Rats after Renal Warm Ischemia-Reperfusion. Int. J. Mol. Sci. 2018, 19, 221.

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