Renal systems biology of patients with systemic inflammatory response syndrome.
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 articleSubject
Acute Kidney InjuryAdult
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
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https://hdl.handle.net/10161/13306Published Version (Please cite this version)
10.1038/ki.2015.150Publication 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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Show full item recordScholars@Duke
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
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
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
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