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Severity of sepsis-induced acute kidney injury in a novel mouse model is age dependent.
MedLine Citation:
PMID:  22743777     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
Bert Maddens; Benjamin Vandendriessche; Dieter Demon; Raymond Vanholder; Koen Chiers; Anje Cauwels; Evelyne Meyer
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-6-28
Journal Detail:
Title:  Critical care medicine     Volume:  -     ISSN:  1530-0293     ISO Abbreviation:  -     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-6-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0355501     Medline TA:  Crit Care Med     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
From the Department of Pharmacology, Toxicology and Biochemistry (BM, DD, EM), Ghent University; Department for Molecular Biomedical Research (BV, AC), VIB; Department of Molecular Biology (BV, AC), Ghent University; Department of Internal Medicine (RV), Renal Division, Ghent University Hospital; Department of Bacteriology, Pathology and Poultry Disease (KC), Ghent University, Ghent, Belgium.
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