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      Identification of Biomarkers of Sepsis-associated Acute Kidney Injury Using Metabolomics Amino Acids Profiling in Intensive Care Unit = Identification of Biomarkers of Sepsis-associated Acute Kidney Injury Using Metabolomics Amino Acids Profiling in Intensive Care Unit

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      Background Acute kidney injury (AKI) following sepsis has been known to be associated with increased mortality. Methods Sepsis or septic shock patients admitted to medical ICU were enrolled from June 2018 through May 2019 at Severance hospital. End st...

      Background
      Acute kidney injury (AKI) following sepsis has been known to be associated with increased mortality.
      Methods
      Sepsis or septic shock patients admitted to medical ICU were enrolled from June 2018 through May 2019 at Severance hospital. End stage renal disease patients on dialysis were excluded. We divided septic patients into those with and without AKI within 48hr after admission to the ICU (D0). Patients with septic AKI were subdivided into AKI recovery and non-recovery groups according to whether kidney injury recovered within 7 days of the initiating event. We collected the serum samples of patients on D0. We used liquid chromatography tandem mass spectrometry (LC-MS/MS) for the application of metabolomics to research, and analyzed the Results to evaluate potential biomarkers of septic AKI.
      Results
      Of the 91 patients, 42 had sepsis, and 49 had septic shock. 84 were included with a median age of 71.0 (IQR 60.9-80.2). Compared with non-AKI and recovery AKI group, non-recovery AKI group showed highest baseline creatine (2.9 vs 1.2 vs 0.8, p<0.001), CCI (4.5 vs 3.0 vs 2.0, p=0.002), SOFA (10.0 vs 8.0 vs 6.5, p<0.001), and APACHE II score (32.0 vs 30.5 vs 21.5, p=0.004). In-hospital (73.3% vs 15.0% vs 23.5%, p<0.001) and 90-day mortality (66.7% vs 20.0% vs 20.6%, p<0.001) were also highest in the non-recovery AKI group. As a result of metabolomics approach using LC-MS/MS, hydroxyproline (14.7 vs 11.3, p≤0.01) and kynurenine (6.6 vs 3.3, p≤0.01) concentration at D0 in non-recovery AKI group were significantly lower than in that in those in non-AKI group. The area under the curve for hydroxyproline and kynurenine for prediction of non-recovery AKI were 0.646 (95% CI 0.517-0.762) and 0.740 (95% CI 0.615-0.842), respectively.
      Conclusions
      Our Results suggest that hydroxyproline and kynurenine could be useful biomarkers for non-recovery AKI diagnosis in sepsis patients in ICU.

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