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

Bert Maddens UGent, Benjamin Vandendriessche, 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
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.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
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
journal title
CRITICAL CARE MEDICINE
Crit. Care Med.
volume
40
issue
9
pages
2638 - 2646
Web of Science type
Article
Web of Science id
000307797700014
JCR category
CRITICAL CARE MEDICINE
JCR impact factor
6.124 (2012)
JCR rank
2/26 (2012)
JCR quartile
1 (2012)
ISSN
0090-3493
DOI
10.1097/CCM.0b013e3182591ebe
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
3096685
handle
http://hdl.handle.net/1854/LU-3096685
date created
2013-01-17 15:25:16
date last changed
2016-12-19 15:46:48
@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},
}

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, B., 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.