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 down-regulated genes. Thus, renal function broadly affected the plasma metabolome, proteome, and peripheral blood transcriptome during critical illness; changes not effectively mitigated by hemodialysis. These studies allude to several novel mechanisms whereby renal dysfunction contributes to critical illness.

Early Diagnosis of Sepsis: Is an Integrated Omics Approach the Way Forward?

“…Metabolomic changes have also been demonstrated to affect immune function in sepsis and renal dysfunction [38, 39]. It was found that patients that presented to the emergency department with sepsis and chronic renal failure had a pan-transcriptomic decrease in expression in white blood cells isolated from septic patients enrolled in the emergency department.…”

“…It was found that patients that presented to the emergency department with sepsis and chronic renal failure had a pan-transcriptomic decrease in expression in white blood cells isolated from septic patients enrolled in the emergency department. Two metabolites allantoin and 4-pyridone-3-carboxamide (4PY) highly correlated with the majority of genes that were decreased due to chronic renal failure in sepsis patients [39]. It was speculated that 4PY, an endogenous inhibitor of poly(ADP-ribose) polymerase 1 (PARP1), could affect transcription in leukocytes.…”

Acute kidney injury is associated with subsequent infection in neonates after the Norwood procedure: a retrospective chart review

“…While it is known that sepsis contributes to AKI, the frequency with which sepsis develops as a consequence of AKI is currently being investigated and has been reported in several adult studies [14–19, 43]. The investigators reported that 45% of non-survivors developed sepsis after the development of contrast-induced AKI [14].…”

Could Biomarkers Direct Therapy for the Septic Patient?

“…A personalized medicine approach may have the best chance of identifying specific strategies for such a diverse patient population. A systems biology approach could complement the use of biomarkers to stratify patients, aid in prognosis, and help identify subsets of patients who may benefit or be harmed by therapy (Tsalik et al, 2015). However, the costs are high, and it is too early to know whether knowledge of the blood metabolome, proteome, and transcriptome could really direct therapy.…”