Cell injury after ischemia and reperfusion in the porcine kidney evaluated by radiolabelled microspheres, sestamibi, and lactadherin

Abstract

Abstract Background The purpose of the present study was to quantify renal cell injury after ischemia and reperfusion in a pig model using 99mTc-lactadherin as a marker of apoptosis and 99mTc-sestamibi as a marker of mitochondrial dysfunction. Methods Thirty-four pigs were randomized into unilateral renal warm ischemia of 120 (WI120) or 240 min (WI240). The glomerular filtration rate (GFR) was calculated by renal clearance of 51Cr-ethylenediaminetetraacetic acid, and apoptosis was quantified by immunohistochemical detection of caspase-3. After 240 min of reperfusion, intravenous 99mTc-lactadherin or 99mTc-sestamibi was injected simultaneously with 153Gd microspheres into the aorta. Ex-vivo static planar images of the kidneys were acquired for determination of the differential renal function of tracer distribution using a gamma camera. Results In WI120, there was no significant difference in the uptake of microspheres in the ischemic and contralateral normal kidney indicating adequate perfusion (uptake in ischemic kidney relative to the sum of uptake in both kidneys; 46% ± 12% and 51% ± 5%). In WI240, the uptake of microspheres was severely reduced in both groups (17% ± 11% and 27% ± 17%). GFR was severely reduced in the post ischemic kidney in both groups. In both groups, the uptake of lactadherin was reduced (41% ± 8%, 17% ± 13%) but not different from the uptake of 153Gd microspheres. Caspase-3-positive cell profiles were increased in the post-ischemic kidneys (p < 0.001) and increased as the length of ischemia increased (p = 0.003). In both WI120 and WI240, the amount of 99mTc-sestamibi in the ischemic kidney was significantly lower than the amount of 153Gd microspheres (40 ± 5 versus 51 ± 5 and 20 ± 11 versus 27 ± 17; p < 0.05). Conclusions In an established pig model with unilateral renal warm ischemia, we found significantly reduced 99mTc-sestamibi uptake relative to perfusion in the kidneys exposed to ischemia indicating a potential ability to detect renal ischemic and reperfusion injuries. However, apoptosis was not detected using 99mTc-lactadherin in the post-ischemic kidneys despite increased number of caspase-3-positive cell profiles. Trial registration This study is approved by the Danish Inspectorate of Animal Experiments (2010/561-1837).