Comparison of ischaemia-reperfusion-induced acute kidney injury by clamping renal arteries, veins or pedicles in anaesthetized rats.

Abstract

What is central question of this study What are the differences between a traditional renal pedicle-clamping model of acute kidney injury and models with occluded renal artery or vein alone in rats? What is main finding and its importance? During renal venous occlusion, transmission of high arterial pressure into renal capillaries is likely to have caused the rupture of their walls and the occurrence of haemorrhagic congestion that led to higher kidney tissue damage and dysfunction than with pedicle and artery clamping. Animal models of ischaemic acute kidney injury (AKI) are valuable tools, but their therapeutic outcomes are not usually translated to humans. Ischaemic AKI in murines is mostly induced via renal pedicle clamping, which is different from patients with AKI that is due to renal artery hypoperfusion or vein thrombosis. This study was designed to compare the traditional pedicle-clamping with artery or vein occlusion alone in rat models of bilateral renal ischaemia-reperfusion (BIR). Twenty-eight anaesthetized male Sprague-Dawley rats were divided into four groups, a sham-operation group and groups that underwent 2h reperfusion following 30min clamping of renal arteries (BIR-A group), veins (BIR-V group) or pedicles (BIR-P group). The levels of epithelial injury in proximal tubules and thick ascending limb, intratubular casts and vascular congestion as well as renal malondialdehyde were moderately lower in the BIR-A than BIR-P group, while the BIR-V group showed much higher degrees of these damages than both these groups along with massive haemorrhagic congestion. Accordingly, renal blood flow, glomerular filtration, Na+ reabsorption, K+ and urea excretion, free water reabsorption and urine osmolality were lower in the BIR-V group than in the BIR-A and BIR-P groups, while the BIR-P group had slightly worse renal functional disorders than the BIR-A group. It seems that transmission of high arterial pressure into renal microvessels during venous occlusion causes rupture of capillary walls and haemorrhagic congestion, which leads to intensive kidney injury. In conclusion, the differences in renal disturbances induced by artery, vein and pedicle clamping strongly suggest use of a proper experimental model for each type of human ischaemic AKI.