Publications by authors named "Stephen Wade Standage"

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NMR-Based Serum and Urine Metabolomic Profile Reveals Suppression of Mitochondrial Pathways in Experimental Sepsis-Associated Acute Kidney Injury.

Am J Physiol Renal Physiol 2021 Apr 12. Epub 2021 Apr 12.

Chemistry and Biochemistry, Miami University, United States.

Sepsis-associated acute kidney injury (SA-AKI) is a significant problem in the critically ill that causes increased death. Emerging understanding of this disease implicates metabolic dysfunction in its pathophysiology. This study sought to identify specific metabolic pathways amenable to potential therapeutic intervention. Using a murine model of sepsis, blood and tissue samples were collected for assessment of systemic inflammation, kidney function, and renal injury. Nuclear magnetic resonance (NMR)-based metabolomics quantified dozens of metabolites in serum and urine which were subsequently submitted to pathway analysis. Kidney tissue gene expression analysis confirmed implicated pathways. Septic mice had elevated circulating levels of inflammatory cytokines and increased levels of blood urea nitrogen and creatinine, indicating both systemic inflammation and poor kidney function. Renal tissue showed only mild histologic evidence of injury in sepsis. NMR metabolomic analysis identified the involvement of mitochondrial pathways associated with branched-chain amino acid (BCAA) metabolism, fatty acid oxidation, and de novo nicotinamide adenine dinucleotide (NAD) biosynthesis in SA-AKI. Renal cortical gene expression of enzymes associated with those pathways was predominantly suppressed. Similar to humans, septic mice demonstrate renal dysfunction without significant tissue disruption, pointing to metabolic derangement as an important contributor to SA-AKI pathophysiology. Metabolism of BCAAs and fatty acids and NAD synthesis, which all center on mitochondrial function, appear to be suppressed. Developing interventions to activate these pathways may provide new therapeutic opportunities for SA-AKI.
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April 2021