Protective effect of everolimus on renal ischemia reperfusion injury in rats

Abstract

The aim of this study was to determine the effect of everolimus and tacrolimus pretreatments on renal morphology and function in a rat ischemia reperfusion (I/R) model. Twenty-eight male Sprague-Dawley rats were randomly assigned to saline + sham operation, saline + I/R (IR), tacrolimus + I/R (TRL + I/R) and everolimus + I/R (ERL + I/R) groups. Saline and active treatments were administered intraperitoneally for seven consecutive days before the surgery. The suprarenal aorta was clamped to achieve warm ischemia, except in the sham group. Right nephrectomy was performed in all animals and histology was examined. Renal function was assessed on post-operative Day 7 by Tc-99m dimercaptosuccinic acid (DMSA) scintigraphy, glomerular filtration rate (GFR) and serum biochemistry. Both everolimus and tacrolimus preserved serum creatinine and blood urea nitrogen levels, but only everolimus preserved GFR (0.74 ± 0.36, 1.20 ± 0.37 and 2.24 ± 0.32 mL/min for I/R, TRL + I/R and ERL + I/R, respectively, P < 0.001). %ID values for sham, I/R, TRL + I/R and ERL + I/R were 55 ± 3, 47 ± 4, 45 ± 6 and 62 ± 7 (P < 0.001). On histologic evaluation, ERL + I/R showed less tubular damage and necrosis than I/R, as well as TRL + I/R. Within the confines of this rat warm ischemia model, everolimus pre-treatment was useful in preserving renal function following I/R injury. The possibility of using everolimus as a pre-conditioning agent for I/R injury in kidney transplantation should be further explored.