Background/aims: Acute kidney injury (AKI) during septic shock, which is one of the most common clinical syndromes in the intensive care unit (ICU), has a high mortality rate and poor prognosis, partly because of a poor understanding of the pathogenesis of renal dysfunction during septic shock. Although ischemic injury of the kidney has been reported to result from adenosine triphosphate (ATP) depletion, increasing evidence has demonstrated that AKI occurs in the absence of renal hypoperfusion and even occurs during normal or increased renal blood flow (RBF); nevertheless, whether energy metabolism disorder is involved in septic AKI and whether it changes according to renal hemodynamics have not been established. Moreover, tubular cell apoptosis, which is closely related to ATP depletion, rather than necrosis, has been shown to be the major form of cell injury during AKI.
Methods: We used canine endotoxin shock models to investigate the hemodynamics, renal energy metabolism, renal oxygen metabolism, and pathological changes during septic AKI and to explore the underlying mechanisms of septic AKI.
Results: The present results revealed that the nicotinamide adenine dinucleotide (NAD+) pool and the ATP/adenosine diphosphate (ADP) ratio were significantly decreased during the early phase of septic AKI, which is accompanied by a decreased renal oxygen extraction ratio (O2ER%) and decreased renal oxygen consumption (VO2). Furthermore, significant apoptosis was observed following renal dysfunction. RBF and renal oxygen delivery were not significantly altered.
Conclusion: These results suggest that imbalanced energy metabolism, rather than tubular cell apoptosis, may be the initiator of renal dysfunction during septic shock.