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Possible prevention and therapy of postischemic (ischemic) acute tubular necrosis

Mark D Okusa, MD
Section Editor
Paul M Palevsky, MD
Deputy Editor
Alice M Sheridan, MD


The renal failure phase in patients with postischemic (also called ischemic) acute tubular necrosis (ATN) typically lasts 7 to 21 days [1], with most patients returning to or near their previous baseline level of renal function as the necrotic tubular cells regenerate. Regenerating tubular cells appear to be mostly derived from dedifferentiated cells (kidney-derived stem cells) that have survived the ischemic insult [2-4]. Migrating bone marrow stem cells may contribute to this process, but to a lesser extent.

The following provides an overview of the different phases of ATN due to ischemia (figure 1):

Initiation phase – Postischemic ATN begins with an early phase of vasomotor nephropathy in which there are associated alterations in vascular reactivity and renal perfusion. These changes lead to cellular adenosine triphosphate (ATP) depletion and oxidative injury.

Extension phase – The changes in the initiation phase lead to activation of resident cells, such as dendritic cells, macrophages, endothelial cells, and renal epithelial cells, leading to a proinflammatory state. Inflammatory cells adhere to activated endothelium in the peritubular capillaries of the outer medulla; this results in medullary congestion and further hypoxic injury to the S3 segment of the proximal tubule. Elaboration of inflammatory mediators leads to additional cellular injury.

Maintenance phase – Restoration of tubule cells is accomplished via several potential mechanisms:


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