Use of ultra high performance liquid chromatography with high resolution mass spectrometry to analyze urinary metabolome alterations following acute kidney injury in post-cardiac surgery patients

Abstract

BackgroundCardiac surgery-associated acute kidney injury (AKI) can increase the mortalityandmorbidity, and the incidence of chronic kidney disease, in critically ill survivors. The purpose of this research was to investigate possible links between urinary metabolic changes and cardiac surgery-associated AKI. MethodsUsing ultra-high-performance liquid chromatography coupled with Q-Exactive Orbitrap mass spectrometry, non-targeted metabolomics was performed on urinary samples collected from groups of patients with cardiac surgery-associated AKI at different time points, including Before_AKI (uninjured kidney), AKI_Day1 (injured kidney) and AKI_Day14 (recovered kidney) groups. The data among the three groups were analyzed by combining multivariate and univariate statistical methods, and urine metabolites related to AKI in patients after cardiac surgery were screened. Altered metabolic pathways associated with cardiac surgery-induced AKI were identified by examining the Kyoto Encyclopedia of Genes and Genomes database. ResultsThe secreted urinary metabolome of the injured kidney can be well separated from the urine metabolomes of uninjured or recovered patients using multivariate and univariate statistical analyses. However, urine samples from the AKI_Day14 and Before_AKI groups cannot be distinguished using either of the two statistical analyses. Nearly 4000 urinary metabolites were identified through bioinformatics methods at Annotation Levels 1–4. Several of these differential metabolites may also perform essential biological functions. Differential analysis of the urinary metabolome among groups was also performed to provide potential prognostic indicators and changes in signalling pathways. Compared with the uninjured kidney group, the patients with cardiac surgery-associated AKI displayed dramatic changes in renal metabolism, including sulphur metabolism and amino acid metabolism. ConclusionsUrinary metabolite disorder was observed in patients with cardiac surgery-associated AKI due to ischaemia and medical treatment, and the recovered patients’ kidneys were able to return to normal. This work provides data on urine metabolite markers and essential resources for further research on AKI.