Sepsis or septic shock is often accompanied by organ dysfunction, among which acute kidney injury (AKI) is the most frequent event that appears early during sepsis. To harness urinary metabolic profiling to discover potential biomarkers of septic acute kidney injury in pediatric patients at intensive care units, we collected urine samples from 27 septic children with AKI and 30 septic children without AKI. We used ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) for profiling and multiple regression analysis to explore the potential biomarkers of sepsis with AKI. We identified a clear distinction in the UPLC-QTOF/MS results for septic children with and without AKI after the development of sepsis, specifically 18 and 17 metabolites with different levels at 12 and 24 h, respectively. Metabolic pathways associated with septic AKI included lipid metabolism, particularly processes involving glycerophospholipid metabolism. L-Histidine, DL-indole-3-lactic acid, trimethylamine N-oxide, and caprylic acid were uncovered as potential biomarkers of septic AKI at 12 h, while gentisaldehyde, 3-ureidopropionate, N4-acetylcytidine, and 3-methoxy-4-hydroxyphenylglycol sulfate were identified as potential candidates at 24 h. We further found that combinations of metabolites were more effective diagnostic marker compared with individual metabolites, with an area under the receiver operating characteristics curve of 0.905 and 0.97 at 12 and 24 h, respectively. Our results indicated that metabolomic analysis could be a promising approach for identifying diagnostic biomarkers of pediatric septic AKI and helped elucidate the pathological mechanisms involved.
Keywords: acute kidney injury; biomarkers; metabolomics; pediatric; sepsis; urine.