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Renal systems biology of patients with systemic inflammatory response syndrome.

Publication ,  Journal Article
Tsalik, EL; Willig, LK; Rice, BJ; van Velkinburgh, JC; Mohney, RP; McDunn, JE; Dinwiddie, DL; Miller, NA; Mayer, ES; Glickman, SW; Jaehne, AK ...
Published in: Kidney Int
October 2015

A systems biology approach was used to comprehensively examine the impact of renal disease and hemodialysis (HD) on patient response during critical illness. To achieve this, we examined the metabolome, proteome, and transcriptome of 150 patients with critical illness, stratified by renal function. Quantification of plasma metabolites indicated greater change as renal function declined, with the greatest derangements in patients receiving chronic HD. Specifically, 6 uremic retention molecules, 17 other protein catabolites, 7 modified nucleosides, and 7 pentose phosphate sugars increased as renal function declined, consistent with decreased excretion or increased catabolism of amino acids and ribonucleotides. Similarly, the proteome showed increased levels of low-molecular-weight proteins and acute-phase reactants. The transcriptome revealed a broad-based decrease in mRNA levels among patients on HD. Systems integration revealed an unrecognized association between plasma RNASE1 and several RNA catabolites and modified nucleosides. Further, allantoin, N1-methyl-4-pyridone-3-carboxamide, and N-acetylaspartate were inversely correlated with the majority of significantly downregulated genes. Thus, renal function broadly affected the plasma metabolome, proteome, and peripheral blood transcriptome during critical illness; changes were not effectively mitigated by hemodialysis. These studies allude to several novel mechanisms whereby renal dysfunction contributes to critical illness.

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Published In

Kidney Int

DOI

EISSN

1523-1755

Publication Date

October 2015

Volume

88

Issue

4

Start / End Page

804 / 814

Location

United States

Related Subject Headings

  • Urology & Nephrology
  • United States
  • Treatment Outcome
  • Time Factors
  • Systems Integration
  • Systems Biology
  • Systemic Inflammatory Response Syndrome
  • Renal Dialysis
  • RNA, Messenger
  • Proteomics
 

Citation

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Tsalik, E. L., Willig, L. K., Rice, B. J., van Velkinburgh, J. C., Mohney, R. P., McDunn, J. E., … Langley, R. J. (2015). Renal systems biology of patients with systemic inflammatory response syndrome. Kidney Int, 88(4), 804–814. https://doi.org/10.1038/ki.2015.150
Tsalik, Ephraim L., Laurel K. Willig, Brandon J. Rice, Jennifer C. van Velkinburgh, Robert P. Mohney, Jonathan E. McDunn, Darrell L. Dinwiddie, et al. “Renal systems biology of patients with systemic inflammatory response syndrome.Kidney Int 88, no. 4 (October 2015): 804–14. https://doi.org/10.1038/ki.2015.150.
Tsalik EL, Willig LK, Rice BJ, van Velkinburgh JC, Mohney RP, McDunn JE, et al. Renal systems biology of patients with systemic inflammatory response syndrome. Kidney Int. 2015 Oct;88(4):804–14.
Tsalik, Ephraim L., et al. “Renal systems biology of patients with systemic inflammatory response syndrome.Kidney Int, vol. 88, no. 4, Oct. 2015, pp. 804–14. Pubmed, doi:10.1038/ki.2015.150.
Tsalik EL, Willig LK, Rice BJ, van Velkinburgh JC, Mohney RP, McDunn JE, Dinwiddie DL, Miller NA, Mayer ES, Glickman SW, Jaehne AK, Glew RH, Sopori ML, Otero RM, Harrod KS, Cairns CB, Fowler VG, Rivers EP, Woods CW, Kingsmore SF, Langley RJ. Renal systems biology of patients with systemic inflammatory response syndrome. Kidney Int. 2015 Oct;88(4):804–814.
Journal cover image

Published In

Kidney Int

DOI

EISSN

1523-1755

Publication Date

October 2015

Volume

88

Issue

4

Start / End Page

804 / 814

Location

United States

Related Subject Headings

  • Urology & Nephrology
  • United States
  • Treatment Outcome
  • Time Factors
  • Systems Integration
  • Systems Biology
  • Systemic Inflammatory Response Syndrome
  • Renal Dialysis
  • RNA, Messenger
  • Proteomics