Experimental ischemia–reperfusion: biases and myths—the proximal vs. distal hypoxic tubular injury debate revisited

Although the understanding of processes associated with hypoxic tubular cell injury has remarkably improved, controversies remain regarding the appropriateness of various animal models to the human syndrome of acute kidney injury (AKI). We herein compare available experimental models of hypoxic acute kidney damage, which differ both conceptually and morphologically in the distribution of tubular cell injury. Tubular segment types differ in their capacity to mount hypoxia-adaptive responses, mediated by hypoxia-inducible factors (HIFs), and in cell type–specific molecules shed into the urine, which may serve as early biomarkers for renal damage. These differences may be of value in the perception of the human AKI, its detection, and prevention.