Abstract 14498: Agonists of Peroxisome Proliferator Activated Receptor Gamma Reduce Renal Ischemia Reperfusion Injury During Aortic Surgery
Introduction: Perioperative acute kidney injury (AKI) during aortic surgery is significantly associated with mortality and morbidity. Intermittent renal perfusion with cold crystalloid during aortic repair has ameliorated renal protection, however, the risk of postoperative hemodialysis remains unsolved.
Hypothesis: We tested our hypothesis that peroxisome proliferator activated receptor gamma (PPAR-γ) plays a role for perioperative AKI, and that PPAR-γ agonists can exert a protective effect against renal ischemia-reperfusion ( I/R) injury as a new strategy for renal protection.
Methods: We investigated the effect of pioglitazone (PGZ), clinically available PPAR-γagonist, in a porcine I/R model. A 60 minute period of warm renal ischemia was induced by bilateral renal artery clamping at 37°C with pigs being sampled before and after the onset of ischemia and 1, 2, 3, 4 hr after reperfusion. The pigs were allocated into 3 groups; control, low dose(5mg/kg) PGZ-treated(LPGZ) group, and high dose(10mg/kg)
PGZ-treated(HPGZ) group (n=6 in each group). The degree of AKI was evaluated by serum neutrophil gelatinase-associated lipocalin (NGAL), AKI biomarker, and pathological findings. The expression and activity of PPAR-γ was evaluated by immunohistochemical staining of PPAR-γ and liver X receptor(LXR)-α, one of its target genes.
Results: The serum NGAL levels were significantly reduced at 3 hr after reperfusion in HPGZ group compared with control(229.5±19.6 vs 397.7±37.4 ng/ml, p<0.05). In pathological findings, departure from normal morphology involving brush border abnormality was reduced in the HPGZ group compared with the other groups. Both PPAR-γ and LXR-α were expressed mainly in the endothelial cells of proximal tubules and expressed stronger in HPGZ group than the other groups.
Conclusions: Pretreatment of pigs with PPAR-γagonist PGZ reduced renal ischemia reperfusion injury with promotion of its expression and activation in kidney.
- © 2013 by American Heart Association, Inc.