Renal systems biology of patients with systemic inflammatory response syndrome.

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

United States

2017-01-01T20:02:00Z

2015-10

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.

http://www.ncbi.nlm.nih.gov/pubmed/25993322

S2157-1716(15)32240-1

1523-1755

https://hdl.handle.net/10161/13306

eng

Elsevier BV

Kidney Int

10.1038/ki.2015.150

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

Renal systems biology of patients with systemic inflammatory response syndrome.

Journal article

Tsalik, Ephraim L|0000-0002-6417-2042

Fowler, Vance G|0000-0002-8048-0897

Woods, Christopher W|0000-0001-7240-2453

http://www.ncbi.nlm.nih.gov/pubmed/25993322

804

814

4

Basic Science Departments

Clinical Science Departments

Duke

Duke Clinical Research Institute

Global Health Institute

Institutes and Centers

Institutes and Provost's Academic Units

Medicine

Medicine, Infectious Diseases

Molecular Genetics and Microbiology

Pathology

School of Medicine

University Institutes and Centers

Published

88