Benzylic rearrangement for urinary analysis of guanidino and ureido compounds in cardiac surgery–associated acute kidney injury using high‐performance liquid chromatography–tandem mass spectrometry

Abstract

RationaleBecause acute kidney injury (AKI) is closely related to poor prognosis in critically ill patients, developing biomarkers for its prediction and early diagnosis is particularly important. Endogenous guanidino compounds (GCs) and ureido compounds (UCs) can participate in various biochemical processes because of their important physiological activities. The aim of this study was to investigate the alteration profiles of urinary GCs/UCs as potential biomarkers in patients with cardiac surgery–associated acute kidney injury (CSA‐AKI) at different stages.MethodsGCs/UCs were reacted with benzil via benzylic rearrangement, and their derivatives were used to investigate fragmentation mechanisms using tandem mass spectrometry (MS/MS) in positive ion mode. Furthermore, a high‐performance liquid chromatography (HPLC)–MS/MS method was developed to measure the concentrations of GCs/UCs in urine samples taken from patients with CSA‐AKI at different time points.ResultsMS/MS analysis in positive ion mode showed that benzylic GCs/UCs exhibited similar fragmentation processes, which could produce the characteristic ion (C13H12N+) at m/z 182.0. Furthermore, an obviously different fragmentation pattern of benzylic UCs in the positive ion mode might be due to the neutral loss of the H2CO2 group under low collision energy. Of the eight selected GCs/UCs, methylguanidine exhibited significantly increased concentrations in urine when CSA‐AKI occurred, whereas guanidinoethyl sulfonate (GDS), homoarginine (HArg) and homocitrulline (HCit) exhibited decreased concentrations. After recovery from AKI, the urinary concentrations of the aforementioned GCs/UCs returned to normal. Some of the aforementioned metabolites with significant changes (GDS, HArg and HCit) had large areas under the curve in the receiver operating characteristic curve for distinguishing AKI stages on the third day after surgery.ConclusionsIn patients with CSA‐AKI, urinary GCs/UCs were significantly disrupted due to injured kidney, and some GC/UC metabolites exhibited a good ability to become potential biomarkers for AKI stages. The present study provides essential resources and new therapeutic targets for further research on CSA‐AKI.