Cellular and molecular derangements in acute tubular necrosis.
OBJECTIVE
Acute tubular necrosis secondary to ischemic acute renal failure remains a common clinical problem with serious consequences and unsatisfactory therapeutic options. The purpose of this review is to summarize recent advances that have provided an improved understanding of the underlying cellular and molecular derangements, and have resulted in the design of novel therapeutic approaches.


RESULTS
Sophisticated morphologic studies have identified apoptosis and vascular changes as significant novel findings in human acute tubular necrosis. Promising roles for inhibitors of apoptosis have been proposed. Activation of tubuloglomerular feedback, previously thought to contribute to acute tubular necrosis, has now emerged as a potentially beneficial phenomenon. The role of reactive oxygen molecules has been further elucidated, and novel antioxidants and iron chelators have been identified. Genome-wide screening techniques have identified the molecular mechanisms underlying the regeneration and repair processes, and have provided clues towards accelerating recovery from acute renal failure. An improved understanding of the role of inflammation has suggested strategies to target this previously underappreciated aspect of acute tubular necrosis.


CONCLUSIONS
The cellular and molecular tools of modern science have provided critical new insights into the roles of apoptosis, oxidant and iron-mediated injury, endothelial changes, regeneration, and the inflammatory response in the pathogenesis of acute tubular necrosis. Novel strategies that modulate these pathways hold tremendous promise for the proactive treatment of human acute renal failure.
Devarajan
Prasad
P
Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, University of Cincinnati School of Medicine, Cincinnati, Ohio 45229, USA. prasad.devarajan@cchmc.org
D058186:Acute Kidney Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D017209:Apoptosis; D016923:Cell Death; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D017136:Ion Transport; D007683:Kidney Tubular Necrosis, Acute / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D015427:Reperfusion Injury / Q000503:physiopathology