Experimental findings in vitro and in vivo illustrate enhanced hypoxia and the formation of reactive oxygen species (ROS) within the kidney following the administration of iodinated contrast media, which may play a role in the development of contrast media-induced nephropathy. Clinical studies indeed support this possibility, suggesting a protective effect of ROS scavenging or reduced ROS formation with the administration of N-acetyl cysteine and bicarbonate infusion, respectively. Furthermore, most risk factors, predisposing to contrast-induced nephropathy are prone to enhanced renal parenchymal hypoxia and ROS formation. In this review, the association of renal hypoxia and ROS-mediated injury is outlined. Generated during contrast-induced renal parenchymal hypoxia, ROS may exert direct tubular and vascular endothelial injury and might further intensify renal parenchymal hypoxia by virtue of endothelial dysfunction and dysregulation of tubular transport. Preventive strategies conceivably should include inhibition of ROS generation or ROS scavenging.

Background and objectives: Renal parenchymal Po₂ declines after the administration of iodinated radiocontrast agents, reaching critically low levels of approximately 10 mmHg in medullary structures.

Renal parenchymal hypoxia, documented under a variety of clinical conditions, conceivably contributes to the progression chronic kidney disease. In this review, normal physiologic medullary hypoxia and abnormal profiles of renal pO(2) in chronic kidney diseases are presented, and the mechanisms leading to anomalous renal tissue oxygenation are discussed. Direct measurements of pO(2) with oxygen electrodes, immunostaining with pimonidazole (which binds to regions with very low pO(2)), or the detection of hypoxia-inducible factor (HIF)-alpha (which accumulates in hypoxic regions, initiating hypoxia-adaptive responses), all serve to detect the distribution and extent of renal parenchymal hypoxia under experimental settings. The use of BOLD MRI as a noninvasive tool, detecting deoxygenated hemoglobin in hypoxic renal tissues, has evolved from experimental settings to human studies. All these modalities indicate that abnormal renal oxygenation develops under conditions such as chronic glomerular, tubulointerstitial or renovascular disease, in diabetes, hypertension, aging, renal hypertrophy, anemia or obstructive uropathy. Abnormal renal tissue hypoxia modifies the pattern of regional gene expression, evoking a host of adaptive and renoprotective pathways (such as HIF-mediated erythropoietin or heme-oxygenase-1), in parallel with the induction of potentially harmful mediators that participate in the progression of chronic kidney injury. Slowing the progression of chronic kidney disease may be achieved by a better understanding of these parallel processes and the accomplishment of a selective control of such protective and maladaptive responses.

The evaluation and management of acute renal failure in the ICU patient remains a formidable task because of the complexity of this condition. Clinical and physiologic assessment and complementing laboratory and imaging tests are currently insufficient to differ between true renal parenchymal damage (acute tubular necrosis; it is important to realize that this term does not necessarily imply widespread injury, because whole organ dysfunction in humans has often been associated with very limited parenchymal cellular necrosis) and prerenal azotemia (decreased renal blood flow with altered glomerular hemodynamics and subsequently diminished glomerular filtration, without significant epithelial cell injury). Moreover, tubular damage and altered glomerular hemodynamics may coexist or lead to each other, and their relative contribution to the evolving renal dysfunction has not been unequivocally established. The limited data regarding the renal pathology of such patients and the scant information about human morphologic and functional correlates further undermine our knowledge about diagnostic and therapeutic approaches to these patients. Advanced techniques are critically needed to establish noninvasively the dynamic status of renal parenchymal microcirculation and the distribution of intrarenal oxygenation and to identify evolving cellular energy depletion and tubular cell damage. A few technologies are potentially promising, such as blood oxygen level dependent magnetic resonance imaging, positron emission tomography, and kidney injury molecule-1 detection in patients' urine. Because of the difficulties in analyzing the pathophysiology in humans, clinicians continue to rely largely on animal models to guide understanding and rationale for the identification of therapeutic targets. Data from such animal studies are complemented by studies in isolated perfused kidneys, isolated tubules, and tubular epithelial cell cultures. In this report, we summarize some concepts of acute tubular necrosis that have evolved as a result of these studies, evaluate available animal models, and underscore controversies regarding experimental acute tubular necrosis.