Renal Hypoxia and Dysoxia After Reperfusion of the Ischemic Kidney

Abstract

Ischemia is the most common cause of acute renal failure. Ischemic-induced renal tissue hypoxia is thought to be a major component in the development of acute renal failure in promoting the initial tubular damage. Renal oxygenation originates from a balance between oxygen supply and consumption. Recent investigations have provided new insights into alterations in oxygenation pathways in the ischemic kidney. These findings have identified a central role of microvascular dysfunction related to an imbalance between vasoconstrictors and vasodilators, endothelial damage and endothelium-leukocyte interactions, leading to decreased renal oxygen supply. Reduced microcirculatory oxygen supply may be associated with altered cellular oxygen consumption (dysoxia), because of mitochondrial dysfunction and activity of alternative oxygen-consuming pathways. Alterations in oxygen utilization and/or supply might therefore contribute to the occurrence of organ dysfunction. This view places oxygen pathways' alterations as a potential central player in the pathogenesis of acute kidney injury. Both in regulation of oxygen supply and consumption, nitric oxide seems to play a pivotal role. Furthermore, recent studies suggest that, following acute ischemic renal injury, persistent tissue hypoxia contributes to the development of chronic renal dysfunction. Adaptative mechanisms to renal hypoxia may be ineffective in more severe cases and lead to the development of chronic renal failure following ischemia-reperfusion. This paper is aimed at reviewing the current insights into oxygen transport pathways, from oxygen supply to oxygen consumption in the kidney and from the adaptation mechanisms to renal hypoxia. Their role in the development of ischemia-induced renal damage and ischemic acute renal failure are discussed.

Acute kidney injury as a causal factor in mortality associated with hepatorenal syndrome

“…Renal hypoxic injury activates the NO system within the mitochondria leading to increased production of free radicals [27]. Tubular-interstitial cell ischemia and hypoxia initiate transcription of proinflammatory cytokines (e.g., such as interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-a) that mediate a cascade of inflammatory reactions causing further injury during renal reperfusion [28][29][30][31][32][33] (Fig.…”

Induction of proinflammatory cytokines and nitric oxide by Trypanosoma cruzi in renal cells

“…After AKI, microvascular dysfunction occurs, mainly through an imbalance between mediators of vasoconstriction and vasodilatation, and NO production is considered to be the main mediator of this process. These deleterious effects are thought to be associated with NO generated by the induction of iNOS and its contribution to oxidative stress (Legrand et al 2008). On the other hand, NO exerts protective effects against ischemic/reperfusion-induced renal dysfunction and degeneration.…”

The Central Role of Renal Microcirculatory Dysfunction in the Pathogenesis of Acute Kidney Injury

“…7% of the total body oxygen consumption), most of which is used by the tubular cells for solute reabsorption [8]. However, under pathological conditions, such as during ischemia-reperfusion, shock, or sepsis, the delicate balance of oxygen supply versus demand is disturbed due to renal microvasculature dysfunction [9]. Microcirculatory dysfunction impedes renal microcirculatory flow at the regional level and this leads to the occurrence of hypoxemic pockets especially in the renal cortex, which is highly heterogeneous even following resuscitation procedures [10].…”