First Report of the Protective Effects of Remote Per- and Postconditioning on Ischemia/Reperfusion-Induced Renal Injury

Abstract

Renal ischemia/reperfusion (IR) is a widespread phenomenon that occurs in many clinical scenarios when blood supply to the kidneys is interrupted and then restored. However, it is the reperfusion, rather than ischemia, that causes the major damage to the organs (1). Remote ischemic conditioning is a powerful method of protection in which brief nonlethal cycles of IR of the arm or leg are applied before (preconditioning), during (perconditioning) (2), or after (postconditioning) (3) prolonged ischemia of a vital distant organ (4, 5). We have recently evaluated the effects of remote ischemic (application of brief episodes of IR in limb) perconditioning and postconditioning (rPeC and rPoC, respectively) during a sustained episode of renal ischemia and reperfusion. Experiments were performed on male Sprague–Dawley rats weighing 250 to 300 g which were randomly assigned into four groups (n 6). All animals underwent right nephrectomy. In IR group, with the use of a nontraumatic vascular clip, 45 min of left renal artery occlusion was induced followed by 24 hr of reperfusion. In sham group, all of the above surgical procedures were applied except that IR was not induced. In rPeC group, four episodes of 5-min ischemia and 5-min reperfusion of left femoral artery (occlusion and release of an arterial clamp) were applied during renal ischemia and before reperfusion. In rPoC group, the same cycles of intermittent IR of left femoral artery were applied after ischemia and right at the time of restoring the blood to the kidney. At the end of the reperfusion, plasma samples were collected for renal functional monitoring by measuring blood concentrations of creatinine and blood urea nitrogen (BUN) by colorimetric methods using commercially available kits. After 24 hr of reperfusion, both rPeC and rPoC significantly improved renal function and prevented the IRinduced increase in BUN and plasma creatinine. As shown in Figure 1, there were significant differences in BUN levels between sham (18 1.29 mg/dL) and IR group (118.4 5.73 mg/dL), between rPeC (49.66 7.24 mg/dL) and IR group, and between rPoC (65.66 6.90 mg/dL) and IR group. Plasma creatinine was also significantly different between sham (0.73 0.16 mg/ dL) and IR group (3.76 0.57 mg/dL), between rPeC (1.43 0.29 mg/dL) and IR group, and between rPoC (2.16 0.71 mg/ dL) and IR group. These data suggest that rPeC and rPoC have protective effects on renal function. Remote ischemic conditionings as noninvasive and applicable methods may be promising strategies against IR injury in clinical practice, especially during renal transplantation.