Title |
Renal systems biology of patients with systemic inflammatory response syndrome
|
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Published in |
Kidney International, May 2015
|
DOI | 10.1038/ki.2015.150 |
Pubmed ID | |
Authors |
Ephraim L. Tsalik, Laurel K. Willig, Brandon J. Rice, Jennifer C. van Velkinburgh, Robert P. Mohney, Jonathan E. McDunn, Darrell L. Dinwiddie, Neil A. Miller, Eric S. Mayer, Seth W. Glickman, Anja K. Jaehne, Robert H. Glew, Mohan L. Sopori, Ronny M. Otero, Kevin S. Harrod, Charles B. Cairns, Vance G. Fowler, Emanuel P. Rivers, Christopher W. Woods, Stephen F. Kingsmore, Raymond J. Langley |
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.Kidney International advance online publication, 20 May 2015; doi:10.1038/ki.2015.150. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 2 | 33% |
Unknown | 4 | 67% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 5 | 83% |
Practitioners (doctors, other healthcare professionals) | 1 | 17% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Italy | 1 | 2% |
Unknown | 64 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 9 | 14% |
Researcher | 7 | 11% |
Other | 5 | 8% |
Student > Bachelor | 5 | 8% |
Student > Doctoral Student | 4 | 6% |
Other | 10 | 15% |
Unknown | 25 | 38% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 15 | 23% |
Biochemistry, Genetics and Molecular Biology | 6 | 9% |
Pharmacology, Toxicology and Pharmaceutical Science | 4 | 6% |
Agricultural and Biological Sciences | 3 | 5% |
Nursing and Health Professions | 2 | 3% |
Other | 8 | 12% |
Unknown | 27 | 42% |