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Kidney Int. 2015 Oct;88(4):804-14. doi: 10.1038/ki.2015.150. Epub 2015 May 20.

Renal systems biology of patients with systemic inflammatory response syndrome.

Author information

1
Emergency Medicine Service, Durham Veterans Affairs Medical Center, Durham, North Carolina, USA.
2
Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.
3
Center for Applied Genomics and Precision Medicine, Duke University School of Medicine, Durham, North Carolina, USA.
4
Center for Pediatric Genomic Medicine, Children's Mercy Hospitals and Clinic, Kansas City, Missouri, USA.
5
National Center for Genome Resources, Santa Fe, New Mexico, USA.
6
Program of Biomedical Sciences and Engineering, University of California, Santa Cruz, Santa Cruz, California, USA.
7
Metabolon, Durham, North Carolina, USA.
8
Department of Pediatrics, Center for Translational Sciences. University of New Mexico, Albuquerque, New Mexico, USA.
9
Department of Emergency Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
10
Department of Emergency Medicine, Henry Ford Hospital, Detroit, Michigan, USA.
11
Department of Surgery, University of New Mexico, Albuquerque, New Mexico, USA.
12
Department of Respiratory Immunology, Lovelace Respiratory Research Institute, Albuquerque, New Mexico, USA.
13
Department of Emergency Medicine, University of Michigan School of Medicine, Ann Arbor, Michigan, USA.
14
Department of Infectious Disease, Lovelace Respiratory Research Institute, Albuquerque, New Mexico, USA.
15
Medicine Service, Durham Veterans Affairs Medical Center, Emergency Medicine, Durham, North Carolina, USA.

Abstract

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.

PMID:
25993322
PMCID:
PMC4591107
DOI:
10.1038/ki.2015.150
[Indexed for MEDLINE]
Free PMC Article

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