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Severity of sepsis-induced acute kidney injury in a novel mouse model is age dependent

Bert Maddens (UGent) , Benjamin Vandendriessche (UGent) , Dieter Demon (UGent) , Raymond Vanholder (UGent) , Koen Chiers (UGent) , Anje Cauwels (UGent) and Evelyne Meyer (UGent)
(2012) CRITICAL CARE MEDICINE. 40(9). p.2638-2646
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Abstract
OBJECTIVE: Despite extensive research, the mortality rate of patients with sepsis-induced acute kidney injury (AKI) is unacceptably high, especially in the elderly. Current sepsis models have difficulties in reproducing AKI. This study aimed to develop a novel, clinically relevant mouse model for sepsis-induced AKI by uterine ligation and inoculation of bacteria. In addition, the age dependency of the severity of sepsis and sepsis-induced AKI was studied by validating this model in three different age categories. DESIGN: Experimental animal investigation. SETTING: University research laboratory. SUBJECTS: Young (12-14 wks), aged (46-48 wks), and old (70-72 wks) C57BL/6 female mice were used as models for adolescent, adult premenopausal, and elderly postmenopausal women, respectively. INTERVENTIONS: Uterine ligation and inoculation with 10 colony forming unit Escherichia coli or saline (sham) was performed; in vivo imaging with a luminescent Escherichia coli strain documented the course of infection. MEASUREMENTS AND MAIN RESULTS: All mice had established Escherichia coli sepsis at 48 hrs postinfection, with higher mortality rate in old (43%) compared to aged (23%) or young (9%) mice. Infected mice had elevated serum or plasma cytokine, chemokine (tumor necrosis factor, interleukin-6, keratinocyte-derived chemokine, monocyte chemoattractant protein 1, and interleukin-10), and NOx concentrations compared to sham mice. AKI was confirmed by renal histology. Serum creatinine concentrations at 48 hrs increased with age (mean ± SEM; controls 0.18 ± 0.03 mg/dL, young 0.28 ± 0.03 mg/dL, aged 0.38 ± 0.05 mg/dL, and old 0.44 ± 0.06 mg/dL). CONCLUSION: The uterine ligation and inoculation model for sepsis-induced AKI starts from a real infectious focus and shows an age-dependent severity of septic AKI that resembles AKI in humans.
Keywords
ACUTE-RENAL-FAILURE, uterus, sepsis, mouse, in vivo imaging, ageing, MORTALITY, ENDOTOXEMIA, DEFINITION, MICE, ILL PATIENTS, CECAL LIGATION, ANIMAL-MODELS, INFLAMMATORY RESPONSE SYNDROME, acute kidney injury, PUNCTURE

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Chicago
Maddens, Bert, Benjamin Vandendriessche, Dieter Demon, Raymond Vanholder, Koen Chiers, Anje Cauwels, and Evelyne Meyer. 2012. “Severity of Sepsis-induced Acute Kidney Injury in a Novel Mouse Model Is Age Dependent.” Critical Care Medicine 40 (9): 2638–2646.
APA
Maddens, Bert, Vandendriessche, B., Demon, D., Vanholder, R., Chiers, K., Cauwels, A., & Meyer, E. (2012). Severity of sepsis-induced acute kidney injury in a novel mouse model is age dependent. CRITICAL CARE MEDICINE, 40(9), 2638–2646.
Vancouver
1.
Maddens B, Vandendriessche B, Demon D, Vanholder R, Chiers K, Cauwels A, et al. Severity of sepsis-induced acute kidney injury in a novel mouse model is age dependent. CRITICAL CARE MEDICINE. 2012;40(9):2638–46.
MLA
Maddens, Bert, Benjamin Vandendriessche, Dieter Demon, et al. “Severity of Sepsis-induced Acute Kidney Injury in a Novel Mouse Model Is Age Dependent.” CRITICAL CARE MEDICINE 40.9 (2012): 2638–2646. Print.
@article{3096685,
  abstract     = {OBJECTIVE: Despite extensive research, the mortality rate of patients with sepsis-induced acute kidney injury (AKI) is unacceptably high, especially in the elderly. Current sepsis models have difficulties in reproducing AKI. This study aimed to develop a novel, clinically relevant mouse model for sepsis-induced AKI by uterine ligation and inoculation of bacteria. In addition, the age dependency of the severity of sepsis and sepsis-induced AKI was studied by validating this model in three different age categories.
DESIGN: Experimental animal investigation.
SETTING: University research laboratory.
SUBJECTS: Young (12-14 wks), aged (46-48 wks), and old (70-72 wks) C57BL/6 female mice were used as models for adolescent, adult premenopausal, and elderly postmenopausal women, respectively.
INTERVENTIONS: Uterine ligation and inoculation with 10 colony forming unit Escherichia coli or saline (sham) was performed; in vivo imaging with a luminescent Escherichia coli strain documented the course of infection.
MEASUREMENTS AND MAIN RESULTS: All mice had established Escherichia coli sepsis at 48 hrs postinfection, with higher mortality rate in old (43\%) compared to aged (23\%) or young (9\%) mice. Infected mice had elevated serum or plasma cytokine, chemokine (tumor necrosis factor, interleukin-6, keratinocyte-derived chemokine, monocyte chemoattractant protein 1, and interleukin-10), and NOx concentrations compared to sham mice. AKI was confirmed by renal histology. Serum creatinine concentrations at 48 hrs increased with age (mean {\textpm} SEM; controls 0.18 {\textpm} 0.03 mg/dL, young 0.28 {\textpm} 0.03 mg/dL, aged 0.38 {\textpm} 0.05 mg/dL, and old 0.44 {\textpm} 0.06 mg/dL).
CONCLUSION: The uterine ligation and inoculation model for sepsis-induced AKI starts from a real infectious focus and shows an age-dependent severity of septic AKI that resembles AKI in humans.},
  author       = {Maddens, Bert and Vandendriessche, Benjamin and Demon, Dieter and Vanholder, Raymond and Chiers, Koen and Cauwels, Anje and Meyer, Evelyne},
  issn         = {0090-3493},
  journal      = {CRITICAL CARE MEDICINE},
  keyword      = {ACUTE-RENAL-FAILURE,uterus,sepsis,mouse,in vivo imaging,ageing,MORTALITY,ENDOTOXEMIA,DEFINITION,MICE,ILL PATIENTS,CECAL LIGATION,ANIMAL-MODELS,INFLAMMATORY RESPONSE SYNDROME,acute kidney injury,PUNCTURE},
  language     = {eng},
  number       = {9},
  pages        = {2638--2646},
  title        = {Severity of sepsis-induced acute kidney injury in a novel mouse model is age dependent},
  url          = {http://dx.doi.org/10.1097/CCM.0b013e3182591ebe},
  volume       = {40},
  year         = {2012},
}

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