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Renal systems biology of patients with systemic inflammatory response syndrome.

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Date
2015-10
Authors
Tsalik, Ephraim L
Willig, Laurel K
Rice, Brandon J
van Velkinburgh, Jennifer C
Mohney, Robert P
McDunn, Jonathan E
Dinwiddie, Darrell L
Miller, Neil A
Mayer, Eric S
Glickman, Seth W
Jaehne, Anja K
Glew, Robert H
Sopori, Mohan L
Otero, Ronny M
Harrod, Kevin S
Cairns, Charles B
Fowler, Vance G
Rivers, Emanuel P
Woods, Christopher W
Kingsmore, Stephen F
Langley, Raymond J
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(21 total)
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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.
Type
Journal article
Subject
Acute Kidney Injury
Adult
Aged
Aged, 80 and over
Biomarkers
Blood Proteins
Critical Illness
Female
Gene Expression Profiling
Gene Expression Regulation
Humans
Kidney
Kidney Function Tests
Male
Metabolomics
Middle Aged
Proteomics
RNA, Messenger
Renal Dialysis
Systemic Inflammatory Response Syndrome
Systems Biology
Systems Integration
Time Factors
Treatment Outcome
United States
Permalink
https://hdl.handle.net/10161/13306
Published Version (Please cite this version)
10.1038/ki.2015.150
Publication Info
Tsalik, Ephraim L; Willig, Laurel K; Rice, Brandon J; van Velkinburgh, Jennifer C; Mohney, Robert P; McDunn, Jonathan E; ... Langley, Raymond J (2015). Renal systems biology of patients with systemic inflammatory response syndrome. Kidney Int, 88(4). pp. 804-814. 10.1038/ki.2015.150. Retrieved from https://hdl.handle.net/10161/13306.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Fowler

Vance Garrison Fowler Jr.

Florence McAlister Distinguished Professor of Medicine
Determinants of Outcome in Patients with Staphylococcus aureus Bacteremia Antibacterial ResistancePathogenesis of Bacterial Infections Tropical medicine/International Health
Tsalik

Ephraim Tsalik

Adjunct Associate Professor in the Department of Medicine
My research at Duke has focused on understanding the dynamic between host and pathogen so as to discover and develop host-response markers that can diagnose and predict health and disease.  This new and evolving approach to diagnosing illness has the potential to significantly impact individual as well as public health considering the rise of antibiotic resistance. With any potential infectious disease diagnosis, it is difficult, if not impossible, to determine at the time of pre
Woods

Christopher Wildrick Woods

Professor of Medicine
1. Emerging Infections 2. Global Health 3. Epidemiology of infectious diseases 4. Clinical microbiology and diagnostics 5. Bioterrorism Preparedness 6. Surveillance for communicable diseases 7. Antimicrobial resistance
Alphabetical list of authors with Scholars@Duke profiles.
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