Urinary proteomics in septic shock complicated with acute kidney injury

Abstract

Objective To identify the early biomarkers of acute kidney injury(AKI) in septic shock patients based on proteomics. Methods A total of 100 patients admitted to the ICU of our hospital with a diagnosis of septic shock between March 2020 and March 2022 were recruited, of whom 42 had concurrent AKI and 58 had no AKI(NAKI). Urine samples were collected from these patients in 12 and 24 h after diagnosis of septic shock. Metabolomic analysis was performed using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-QTOF/MS). Comparative cluster analysis was used to identify the global proteomic patterns associated with injury severity, and then to identify the early biomarkers of septic shock combined with AKI. Urine samples were analyzed the contents of neutrophil gelatinase-associated lipocalin(NGAL), chitinase-like protein 3(Chil3), S100 calcium binding protein A8(S100A8) and ceruloplasmin(CP) with ELISA kits. Biomarker performance was quantified by plotting receiver operating characteristic(ROC) curves. Results The AKI group had significantly higher SCr and lactate levels and increased all-cause mortality (P < 0.05), and obviously lower eGFR than the NAKI group(P < 0.001). Metabolomic analysis revealed that the levels of proteins associated with extracellular matrix and acute-phase responses were increased after diagnosis of septic shock, while the levels of proteins associated with excretion of ions, amino acids, and metabolites, and mitochondria-associated proteins were decreased in the AKI patients. Global proteome pattern analysis revealed that NGAL, Chil3, S100A8 and CP were early biomarkers of septic shock complicated with AKI. The results of ELISA indicated that NGAL, Chil3, S100A8 and CP in AKI patients with septic shock were significantly higher than those without AKI(P < 0.05). Correlation analysis showed that the expression levels of NGAL, Chil3, S100A8 and CP were positively correlated with SCr level(r=0.276, 0.391, 0.789, 0.721, all P < 0.001). ROC analysis suggested that the combination of these markers had greater diagnostic performance in diagnosing septic shock complicated with AKI, and the AUCs at 12 h and 24 h were 0.901 and 0.958, respectively. Conclusion NGAL, Chil3, S100A8 and CP based on proteomics can be used as early biomarkers for identifying septic shock complicated with AKI.

Keywords

• proteomics
• septic shock
• acute kidney failure
• biomarkers