Renal systems biology of patients with systemic inflammatory response syndrome.
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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.
SubjectAcute Kidney Injury
Aged, 80 and over
Gene Expression Profiling
Gene Expression Regulation
Kidney Function Tests
Systemic Inflammatory Response Syndrome
Published Version (Please cite this version)10.1038/ki.2015.150
Publication InfoTsalik, 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.
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Florence McAlister Distinguished Professor of Medicine
Determinants of Outcome in Patients with Staphylococcus aureus Bacteremia Antibacterial ResistancePathogenesis of Bacterial Infections Tropical medicine/International Health
Associate Professor of Medicine
My research is 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 presentation
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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