Renal oxygenation in acute renal ischemia-reperfusion injury

Abstract

Tissue hypoxia has been demonstrated, in both the renal cortex and medulla, during the acute phase of reperfusion after ischemia induced by occlusion of the aorta upstream from the kidney. However, there are also recent clinical observations indicating relatively well preserved oxygenation in the nonfunctional transplanted kidney. To test whether severe acute kidney injury can occur in the absence of widespread renal tissue hypoxia, we measured cortical and inner medullary tissue Po2 as well as total renal O2 delivery (Do2) and O2 consumption (Vo2) during the first 2 h of reperfusion after 60 min of occlusion of the renal artery in anesthetized rats. To perform this experiment, we used a new method for measuring kidney Do2 and Vo2 that relies on implantation of fluorescence optodes in the femoral artery and renal vein. We were unable to detect reductions in renal cortical or inner medullary tissue Po2 during reperfusion after ischemia localized to the kidney. This is likely explained by the observation that Vo2 (-57%) was reduced by at least as much as Do2 (-45%), due to a large reduction in glomerular filtration (-94%). However, localized tissue hypoxia, as evidence by pimonidazole adduct immunohistochemistry, was detected in kidneys subjected to ischemia and reperfusion, particularly in, but not exclusive to, the outer medulla. Thus, cellular hypoxia, particularly in the outer medulla, may still be present during reperfusion even when reductions in tissue Po2 are not detected in the cortex or inner medulla.

Inflammation: A Key Contributor to the Genesis and Progression of Chronic Kidney Disease

“…The areas of hypoxia are subject to reperfusion injury. A sustained state of inflammation has been observed at the hypoxia-normoxia borders [7,8] . These inflammation-mediated changes, when severe, can induce irreversible tubular injury and nephron dropout.…”

Hypoxia: The Force that Drives Chronic Kidney Disease

“…[240][241][242] Induction of AKI in animals by ischemia, radiocontrast agents, cisplatin, or rhabdomyolysis all induce oxygen tensions below 10 mm Hg deep within kidney tissue. 95,[243][244][245][246][247] In addition, impaired renal oxygenation has also been observed in human AKI. 248 Importantly, renal hypoxia is found not only during the acute phase of AKI but also up to 5 weeks later, after the recovery phase.…”

Renal Hemodynamics in AKI

“…However, mean microcirculatory pO2 showed no changes; a demonstration of the overall heterogeneity of ischemia is in Johannes et al 43 Similar results were obtained in an ischemia-reperfusion model of AKI, where mean tissue pO2 measured using oxygen electrodes showed no change, whereas the hypoxiasensitive pimonidazole adduct immunohistochemistry was able to identify microheterogenous hypoxic areas. 44 In addition to these effects, the patchy distribution of microvascular changes might affect both the glomerular and peritubular circulations. As a result, zones of nephrons with glomerular hypofiltration and peritubular capillary occlusion might coexist with clusters of normal or even hyperfiltrating atrisk nephrons.…”