Plasma indole-3-aldehyde as a novel biomarker of acute kidney injury after cardiac surgery: a reanalysis using prospective metabolomic data

Abstract Background Acute kidney injury (AKI) is a frequent complication of cardiac surgery that poses significant risks for both the development of chronic kidney diseases and mortality. Our previous study illustrated that heightened expression levels of faecal and plasma indole metabolites before the operation were associated with ischemic AKI. In this study, we aimed to validate the supposition that plasma indole-3-aldehyde (I3A) could serve as a predictive biomarker for AKI in patients undergoing cardiac surgery. Methods This statistical reanalysis utilized AKI metabolomic data from patients scheduled for cardiac surgery between April 2022 and July 2022 in two tertiary hospitals. Faecal and blood samples were prospectively collected before surgery within 24 h, and variables related to the preoperative, intraoperative, and postoperative periods were recorded. AKI diagnosis was based on the Kidney Disease Improving Global Outcomes criteria. Results In this study, 55 patients who underwent cardiac surgery were analyzed, and 27 of them (49.1%) developed postoperative AKI. Before surgery, these patients had significantly higher levels of faecal indole metabolites, including skatole, trans-3-indoleacrylic acid, and 5-methoxyindoleacetic acid. The plasma I3A, clinical model that considered perioperative and intraoperative variables, and their combination had area under the receiver operating characteristic curve (ROC) values of 0.79 (95% CI 0.67–0.91), 0.78 (95% CI 0.66–0.90), and 0.84 (95% CI 0.74–0.94) for predicting AKI, respectively. Furthermore, by utilizing net reclassification improvement and integrated discrimination improvement, plasma I3A showed significant improvements in risk reclassification compared to the clinical model alone. Conclusions The dysregulation of gut microbiota metabolism in patients scheduled for cardiac surgery can result in an increase in indoles from tryptophan metabolism, which may be associated with postoperative acute kidney injury (AKI). This suggests that indoles may serve as a predictive biomarker for AKI in patients undergoing cardiac surgery.