Renal systems biology of patients with systemic inflammatory response syndrome.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • 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

Published Date

  • October 2015

Published In

Volume / Issue

  • 88 / 4

Start / End Page

  • 804 - 814

PubMed ID

  • 25993322

Pubmed Central ID

  • 25993322

Electronic International Standard Serial Number (EISSN)

  • 1523-1755

Digital Object Identifier (DOI)

  • 10.1038/ki.2015.150

Language

  • eng

Conference Location

  • United States