Energy and Oxygen Metabolism Disorder During Septic Acute Kidney Injury

Abstract

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.

Inhibition of Poly-(ADP-Ribose) Polymerase Protects the Kidney in a Canine Model of Endotoxic Shock

“…All surgeries were performed according to previous study [16]. Anesthesia was induced by intraperitoneal injection of pentobarbital (30 mg/kg), and continuous administration was maintained by using a mini pump (pentobarbital, 4 mg/kg/h).…”

“…In the LPS + 3AB group, injection of 3-AB (Sigma-Aldrich, Mo., USA, 15 mg/kg [18], determined by preliminary test) was performed when the vital signs of canines were stable after operation (about 30 min), while canines in the control group accepted saline injection in the same way. In the LPS groups, input of LPS (Escherichia coli O55:B5, Sigma-Aldrich, Mo., USA) (2 mg/kg [16,19], at 1 mg/kg·min) was conducted through the pulmonary artery catheter 10 min after the administration of 3-AB or saline. Kidney samples were harvested 0, 2, 4 and 6 h after LPS injection in the LPS groups and 6 h after in control and LPS + 3AB group.…”

“…Renal cortex, corticomedulllary border, medulla layer and inner medulla were observed by Olympus IX51optical microscopy (OLYMPUS IX51, JAPAN). Semi-quantitative scores [16] was used to evaluate the percentage of tubular cell injury including the loss of brush border, vacuolization, cast formation and tubule dilation; and score was calculated as follows: 0 (none, 1-10%), 2 (11-25%), 3 (26-45%), 4 (46-75%) and 5 (>76%). For each canine, at least 10 high-power fields were examined.…”

“…Energy substances measurement was conducted according to previous studies [16] using high-performance liquid chromatography (HPLC; Waters Alliance, USA) [20,21]. Briefly, renal tissues from all groups were preserved in liquid nitrogen within seconds after sampling.…”

Detrimental Cross-Talk Between Sepsis and Acute Kidney Injury: New Pathogenic Mechanisms, Early Biomarkers and Targeted Therapies

“…In response to these deleterious stimuli, tubular cells dedifferentiate and release a plethora of paracrine factors as an ultimate effort to induce tissue regeneration. On the other hand, tubular cells directly contribute to systemic inflammation by carrying out immune functions, such as cytokine release and leukocyte recruitment and activation been found that during sepsis, renal oxygen consumption is significantly reduced [17]. The auto-digestion of energy-consuming organelles (autophagy), including the mitochondria (mitophagy), is one of the key passages of this biological phenomenon.…”