Evaluating acetate as a renoprotective agent following kidney ischemia in a porcine model.

Abstract

OBJECTIVE Renoprotection from reperfusion injury appears to be conferred by HIF-2A activation, which can be stimulated by exogenous acetate administration. The study objective was to assess whether administration of acetate in a porcine model can mitigate kidney injury related to ischemia-reperfusion following renal hilar occlusion. METHODS A porcine single-kidney model was created by performing a laparoscopic nephrectomy followed by animal recovery. After seven days, the animals underwent laparoscopic hilar dissection. Block randomization was used to assign pigs into one of four experimental groups. One treatment block of pigs received 150 mEq of sodium acetate intravenously during 90 minutes of en bloc occlusion of the renal hilum (herein noted as 'cross clamping'). Another block received 0.75 g/kg of oral sodium acetate for three days prior to cross clamping. A third block received no acetate and underwent hilar dissection without cross clamping (negative control). The final block received no acetate and underwent cross clamping (positive control). Serum creatinine was used to estimate renal function post-nephrectomy. RESULTS A total of 16 animals (4 pigs in each group), completed the study protocol. Median pig weight was 34.6 kg. One pig receiving IV acetate was excluded from the final analysis due to unrecoverable renal failure following cross-clamping. There was a significantly lower mean serum creatinine for the IV acetate group compared to the positive control group 72 hours after cross clamp (p=0.012). The same effect was not observed for the pigs receiving oral acetate. By day 7, renal function recovered without significant difference in all groups. CONCLUSIONS We observed that the administration of intravenous acetate conferred a significant renoprotective benefit in our single kidney ischemia-reperfusion porcine model 72 hours following hilar occlusion. This work is hypothesis-generating and further work in human subjects undergoing renal hilar occlusion during partial nephrectomy is warrante.