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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)
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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.
Keywords
MICE, MARKER, DIAGNOSIS, GLOMERULOSCLEROSIS, KeyWords Plus: GELATINASE-ASSOCIATED LIPOCALIN, URINARY BIOMARKERS, ACUTE-RENAL-FAILURE, GLOMERULOSCLEROSIS, DISEASE, YKL-40, PROTEOMICS

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MLA
Maddens, Bert, et al. “Chitinase-like Proteins Are Candidate Biomarkers for Sepsis-Induced Acute Kidney Injury.” MOLECULAR & CELLULAR PROTEOMICS, vol. 11, no. 6, 2012, doi:10.1074/mcp.M111.013094.
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). https://doi.org/10.1074/mcp.M111.013094
Chicago author-date
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). https://doi.org/10.1074/mcp.M111.013094.
Chicago author-date (all authors)
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). doi:10.1074/mcp.M111.013094.
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).
IEEE
[1]
B. Maddens et al., “Chitinase-like proteins are candidate biomarkers for sepsis-induced acute kidney injury,” MOLECULAR & CELLULAR PROTEOMICS, vol. 11, no. 6, 2012.
@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 Ghesquière, Bart and Vanholder, Raymond and Demon, Dieter and Vanmassenhove, J and Gevaert, Kris and Meyer, Evelyne}},
  issn         = {{1535-9476}},
  journal      = {{MOLECULAR & CELLULAR PROTEOMICS}},
  keywords     = {{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://doi.org/10.1074/mcp.M111.013094}},
  volume       = {{11}},
  year         = {{2012}},
}

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