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Chitinase-like proteins are candidate biomarkers for sepsis-induced acute kidney injury

Bert Maddens UGent, Bart Ghesquière UGent, Raymond Vanholder UGent, Dieter Demon UGent, J Vanmassenhove, Kris Gevaert UGent and Evelyne Meyer UGent (2012) MOLECULAR & CELLULAR PROTEOMICS. 11(6).
abstract
Sepsis-induced acute kidney injury (AKI) is a frequent complication of critically ill patients and leads to high mortality rates. The specificity of currently available urinary biomarkers for AKI in the context of sepsis is questioned. This study aimed to discover urinary biomarkers for septic AKI by contemporary shotgun proteomics in a mouse model for sepsis and to validate these in individual urine samples of mice and human septic patients with and without AKI. At 48 h after uterine ligation and inoculation of Escherichia coli, aged mice (48 weeks) became septic. A subgroup developed AKI, defined by serum creatinine, blood urea nitrogen, and renal histology. Separate pools of urine from septic mice with and without AKI mice were collected during 12 h before and between 36-48 h after infection, and their proteome compositions were quantitatively compared. Candidate biomarkers were validated by Western blot analysis of urine, plasma, and renal tissue homogenates from individual mice, and a limited number of urine samples from human septic patients with and without AKI. Urinary neutrophil gelatinase-associated lipocalin, thioredoxin, gelsolin, chitinase 3-like protein 1 and -3 (CHI3L3) and acidic mammalian chitinase were the most distinctive candidate biomarkers selected for septic AKI. Both neutrophil gelatinase-associated lipocalin and thioredoxin were detected in urine of septic mice and increased with severity of AKI. Acidic mammalian chitinase was only present in urine of septic mice with AKI. Both urinary chitinase 3-like protein 1 and -3 were only detected in septic mice with severe AKI. The human homologue chitinase 3-like protein 1 was found to be more excreted in urine from septic patients with AKI than without. In summary, urinary chitinase 3-like protein 1 and -3 and acidic mammalian chitinase discriminated sepsis from sepsis-induced AKI in mice. Further studies of human chitinase proteins are likely to lead to additional insights in septic AKI. Molecular & Cellular Proteomics 11: 10.1074/mcp.M111.013094, 1-13, 2012.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
MICE, MARKER, DIAGNOSIS, GLOMERULOSCLEROSIS, KeyWords Plus: GELATINASE-ASSOCIATED LIPOCALIN, URINARY BIOMARKERS, ACUTE-RENAL-FAILURE, GLOMERULOSCLEROSIS, DISEASE, YKL-40, PROTEOMICS
journal title
MOLECULAR & CELLULAR PROTEOMICS
Mol. Cell. Proteomics
volume
11
issue
6
pages
13 pages
Web of Science type
Article
Web of Science id
000306408500012
JCR category
BIOCHEMICAL RESEARCH METHODS
JCR impact factor
7.251 (2012)
JCR rank
5/74 (2012)
JCR quartile
1 (2012)
ISSN
1535-9476
DOI
10.1074/mcp.M111.013094
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
2972481
handle
http://hdl.handle.net/1854/LU-2972481
date created
2012-08-16 15:29:25
date last changed
2012-09-04 10:35:07
@article{2972481,
  abstract     = {Sepsis-induced acute kidney injury (AKI) is a frequent complication of critically ill patients and leads to high mortality rates. The specificity of currently available urinary biomarkers for AKI in the context of sepsis is questioned. This study aimed to discover urinary biomarkers for septic AKI by contemporary shotgun proteomics in a mouse model for sepsis and to validate these in individual urine samples of mice and human septic patients with and without AKI. At 48 h after uterine ligation and inoculation of Escherichia coli, aged mice (48 weeks) became septic. A subgroup developed AKI, defined by serum creatinine, blood urea nitrogen, and renal histology. Separate pools of urine from septic mice with and without AKI mice were collected during 12 h before and between 36-48 h after infection, and their proteome compositions were quantitatively compared. Candidate biomarkers were validated by Western blot analysis of urine, plasma, and renal tissue homogenates from individual mice, and a limited number of urine samples from human septic patients with and without AKI. Urinary neutrophil gelatinase-associated lipocalin, thioredoxin, gelsolin, chitinase 3-like protein 1 and -3 (CHI3L3) and acidic mammalian chitinase were the most distinctive candidate biomarkers selected for septic AKI. Both neutrophil gelatinase-associated lipocalin and thioredoxin were detected in urine of septic mice and increased with severity of AKI. Acidic mammalian chitinase was only present in urine of septic mice with AKI. Both urinary chitinase 3-like protein 1 and -3 were only detected in septic mice with severe AKI. The human homologue chitinase 3-like protein 1 was found to be more excreted in urine from septic patients with AKI than without. In summary, urinary chitinase 3-like protein 1 and -3 and acidic mammalian chitinase discriminated sepsis from sepsis-induced AKI in mice. Further studies of human chitinase proteins are likely to lead to additional insights in septic AKI. Molecular \& Cellular Proteomics 11: 10.1074/mcp.M111.013094, 1-13, 2012.},
  author       = {Maddens, Bert and Ghesqui{\`e}re, Bart and Vanholder, Raymond and Demon, Dieter and Vanmassenhove, J and Gevaert, Kris and Meyer, Evelyne},
  issn         = {1535-9476},
  journal      = {MOLECULAR \& CELLULAR PROTEOMICS},
  keyword      = {MICE,MARKER,DIAGNOSIS,GLOMERULOSCLEROSIS,KeyWords Plus: GELATINASE-ASSOCIATED LIPOCALIN,URINARY BIOMARKERS,ACUTE-RENAL-FAILURE,GLOMERULOSCLEROSIS,DISEASE,YKL-40,PROTEOMICS},
  language     = {eng},
  number       = {6},
  pages        = {13},
  title        = {Chitinase-like proteins are candidate biomarkers for sepsis-induced acute kidney injury},
  url          = {http://dx.doi.org/10.1074/mcp.M111.013094},
  volume       = {11},
  year         = {2012},
}

Chicago
Maddens, Bert, Bart Ghesquière, Raymond Vanholder, Dieter Demon, J Vanmassenhove, Kris Gevaert, and Evelyne Meyer. 2012. “Chitinase-like Proteins Are Candidate Biomarkers for Sepsis-induced Acute Kidney Injury.” Molecular & Cellular Proteomics 11 (6).
APA
Maddens, B., Ghesquière, B., Vanholder, R., Demon, D., Vanmassenhove, J., Gevaert, K., & Meyer, E. (2012). Chitinase-like proteins are candidate biomarkers for sepsis-induced acute kidney injury. MOLECULAR & CELLULAR PROTEOMICS, 11(6).
Vancouver
1.
Maddens B, Ghesquière B, Vanholder R, Demon D, Vanmassenhove J, Gevaert K, et al. Chitinase-like proteins are candidate biomarkers for sepsis-induced acute kidney injury. MOLECULAR & CELLULAR PROTEOMICS. 2012;11(6).
MLA
Maddens, Bert, Bart Ghesquière, Raymond Vanholder, et al. “Chitinase-like Proteins Are Candidate Biomarkers for Sepsis-induced Acute Kidney Injury.” MOLECULAR & CELLULAR PROTEOMICS 11.6 (2012): n. pag. Print.