Sepsis results in an altered renal metabolic and osmolyte profile

Sepsis remains a major health-care burden and source of morbidity and mortality. Acute kidney injury and failure frequently accompanies severe sepsis and contributes to this burden. Despite a great deal of research, the exact mechanisms underlying renal failure in sepsis are poorly understood. This study aims to further understand metabolic changes in renal tissue during sepsis.

Experimental sepsis was induced by cecal ligation and puncture (CLP) in C57BL/6 mice. Serum and organs were harvested 8 h after CLP. Markers of renal function including serum creatinine, blood urea nitrogen, and cystatin C were measured. Whole kidneys were analyzed for a global biochemical profile via liquid chromatography/tandem mass spectrometry by Metabolon.

CLP induced renal injury as evidenced by elevated serum creatinine, blood urea nitrogen, and cystatin C. Global energetic profile in sepsis showed an increase in glycolytic intermediates with decreased flux through the tricarboxylic acid (TCA) cycle. Multiple inflammatory markers were elevated in response to CLP. Levels of osmotic regulators varied, with an overall increase in pinitol, urea, and taurine in response to CLP.

CLP resulted in dramatic changes in the renal macromolecular milieu. There appears to be an increased dependence on glycolysis and diminished flush through the TCA cycle. In addition, changes in renal osmolytes including pinitol, urea, and taurine were observed, perhaps uncovering an additional change with implications on renal function during sepsis.