Acute kidney injury: lessons from experimental models.
For decades severe tubular necrosis has been the hallmark of experimental models of acute renal failure (ARF), such as prolonged ischemia and reflow. This fits well with the still widely used traditional clinical term 'acute tubular necrosis'. Nevertheless, the rareness of tubular necrosis in human kidney biopsies in the background of hypoxic, toxic and septic AKI led to the adoption of a new term, 'acute kidney injury' (AKI), which refers to such clinical scenarios irrespective of the renal morphology. Indeed, experimental AKI models, which have more limited acute renal parenchymal compromise, underscore the focal and regional tissue injury patterns that range from adaptive stress response, through cellular dysfunction, apoptotic cell death and frank acute tubular necrosis. Such stress and injury patterns, short of necrosis, may go unnoticed morphologically and even functionally, and may even confer resistance to subsequent insults. Herein we describe the spectrum of what we call 'sublethal injury', referring to a condition, which by itself is insufficient to produce cellular death, but may or may not produce organ failure. Such sublethal injury can be detected by overt morphological changes, by the upregulation of cell survival factors, and by recently developed biomarkers and imaging techniques of organ physiology and dysfunction. The use of combined sublethal insults in animal models is an attempt to replicate the clinical situation of comorbidities, a circumstance which underlies most situations of AKI. This review will discuss the definition of such sublethal injury and the modes of its detection.
Samuel N
SN
Heyman
Christian
C
Rosenberger
Seymour
S
Rosen
D058186:Acute Kidney Injury / Q000175:diagnosis / Q000473:pathology* / Q000503:physiopathology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D004195:Disease Models, Animal; D006801:Humans; D007683:Kidney Tubular Necrosis, Acute / Q000473:pathology / Q000503:physiopathology