Abstract 13830: Hypercholesterolaemia Prevents Post Cardiopulmonary Bypass Acute Kidney Injury in Swine via Activation of the Akt/ mTor Pathway
Background Hypercholesterolaemia (HC), an established aetiological factor in the development of chronic kidney disease (CKD) has also been associated with increased risk for acute kidney injury in clinical studies. We sought to establish how HC induced by a 12-week diet of 2% cholesterol, 15% lard and cholic acid would influence the development of post cardiopulmonary bypass (CPB) acute kidney injury in a swine model.
Methods and Results Twenty eight adult pigs undergoing general anaesthesia were allocated to Sham procedure, CPB, HC + Sham, or HC + CPB, with recovery and reassessment at 24 hours. Pre-intervention mean (standard deviation) total cholesterol levels in HC and non HC pigs were 11.4 (0.6) mmol/L and 1.5 (0.7) mmol/L respectively. CPB caused acute kidney injury as defined by reductions in creatinine clearance from baseline, loss of nitric oxide (NO) bioavailability, elevated cortical adenosine levels, endothelial dysfunction, depletion of adenosine triphosphate (ATP), sequestration of inflammatory cells and proximal tubule epithelial cell stress manifest as increased inducible NO synthase (iNOS) expression (Table 1). HC + Sham pigs had similar creatinine clearance, renal haemodynamics, NO and adenosine levels to non-HC Sham pigs but demonstrated increased expression of the serine/threonine kinase Akt, activation of downstream effectors of the mTOR pathway and increased iNOS expression. HC+CPB pigs also demonstrated activation of Akt/mTOR with HC preventing the renal dysfunction attributable to CPB in association with significantly increased renal blood flow and ATP levels similar to those in Sham and Sham+ HC groups .
Conclusion Hypercholesterolaemia prevents post CPB acute kidney injury in swine. The Akt/ mTOR pathway may represent a therapeutic target for renoprotective strategies in cardiac surgery.
- © 2011 by American Heart Association, Inc.