Plasma Linoleic Acid Is Associated With Pediatric Sepsis Phenotype and Acute Kidney Injury

OBJECTIVES: Linoleic acid (LA) is the most abundant polyunsaturated fatty acid in diet, and it is a precursor to inflammatory lipid mediators called oxylipins. The role of LA and its oxylipins in pediatric sepsis and organ injury is uncertain. Recently, pediatric sepsis phenotypes were described, with phenotype D characterized by the highest proportion of acute kidney injury (AKI), multiple organ failure, and risk of death. We aimed to test the hypothesis LA may play a role in sepsis-associated organ dysfunction. We therefore investigated whether increasing plasma LA and LA-derived lipoxygenase oxylipins are associated with sepsis phenotype D and with AKI in a cohort of critically ill children with sepsis. DESIGN: We studied a subset of 108 patients from the Phenotyping Sepsis-Induced Multiple Organ Failure Study (PHENOMS) cohort by means of untargeted metabolomics of heparinized plasma samples. Primary outcome was phenotype group. Key secondary outcomes included AKI (defined as both creatinine > 1 mg/dL and oliguria < 0.5 mL/kg/hr), other organ dysfunctions, and hospital mortality. Patients were followed up until discharge or 28 days. SETTING: ICU. PATIENTS: One hundred eight patients with sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Higher LA levels were associated with sepsis phenotype D as compared with phenotypes A-C (odds ratio [OR], 1.67; 95% CI, 1.05-2.65; p = 0.03). LA-derived oxylipins 9-hydroxyoctadecadienoic acid and 13-hydroxyoctadecadienoic acid (9-HODE/13-HODE) were also associated with sepsis phenotype D (jointly reported in one variable; OR, 1.26; 95% CI, 1.01-1.57; p = 0.04). Higher LA showed a trend and 9-HODE/13-HODE was associated with AKI (OR, 1.52; 95% CI, 0.97-2.38; p = 0.07 and OR, 1.27; 95% CI, 1.03-1.56; p = 0.02, respectively). Neither LA nor oxylipins were associated with hospital mortality. CONCLUSIONS: LA levels and LA-derived lipoxygenase oxylipins are associated with pediatric sepsis phenotype D and AKI. These results support future mechanistic studies to investigate lipid metabolism in the pathophysiology of sepsis.