Journal article
Renal systems biology of patients with systemic inflammatory response syndrome
Kidney international, v 88(4), pp 804-814
01 Oct 2015
PMID: 25993322
Featured in Collection : UN Sustainable Development Goals @ Drexel
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.
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Details
- Title
- Renal systems biology of patients with systemic inflammatory response syndrome
- Creators
- Ephraim L. Tsalik - Durham VA Medical CenterLaurel K. Willig - Children's Mercy HospitalBrandon J. Rice - National Center for Genome ResourcesJennifer C. van Velkinburgh - National Center for Genome ResourcesRobert P. Mohney - Metabolon (United States)Jonathan E. McDunn - Metabolon (United States)Darrell L. Dinwiddie - National Center for Genome ResourcesNeil A. Miller - Children's Mercy HospitalEric S. Mayer - Metabolon (United States)Seth W. Glickman - University of North Carolina at Chapel HillAnja K. Jaehne - Henry Ford HospitalRobert H. Glew - University of New MexicoMohan L. Sopori - Lovelace Respiratory Research InstituteRonny M. Otero - Henry Ford HospitalKevin S. Harrod - Lovelace Respiratory Research InstituteCharles B. Cairns - University of North Carolina at Chapel HillVance G. Fowler - Duke Medical CenterEmanuel P. Rivers - Henry Ford HospitalChristopher W. Woods - Duke Medical CenterStephen F. Kingsmore - National Center for Genome ResourcesRaymond J. Langley - National Center for Genome Resources
- Publication Details
- Kidney international, v 88(4), pp 804-814
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine
- Web of Science ID
- WOS:000362219600021
- Scopus ID
- 2-s2.0-84942982512
- Other Identifier
- 991021448050504721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- Web of Science research areas
- Urology & Nephrology