Renal systems biology of patients with systemic inflammatory response syndrome. Kidney Int 2015 Oct;88(4):804-14
Date
05/21/2015Pubmed ID
25993322Pubmed Central ID
PMC4591107DOI
10.1038/ki.2015.150Scopus ID
2-s2.0-84942982512 (requires institutional sign-in at Scopus site) 35 CitationsAbstract
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.
Author List
Tsalik EL, Willig LK, Rice BJ, van Velkinburgh JC, Mohney RP, McDunn JE, Dinwiddie DL, Miller NA, Mayer ES, Glickman SW, Jaehne AK, Glew RH, Sopori ML, Otero RM, Harrod KS, Cairns CB, Fowler VG, Rivers EP, Woods CW, Kingsmore SF, Langley RJAuthor
Ronny M. Otero MD Vice Chair, Professor in the Emergency Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
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
