Quantitative Proteomic and Metabolomic Profiling Reveals Altered Purine Metabolism in Acute Kidney Injury after On-Pump Coronary Artery Bypass Graft.

Abstract

Acute kidney injury (AKI) is a frequent complication following on-pump coronary artery bypass graft surgery (CABG). To better investigate the effect of CABG on kidney function and the pathological process of AKI during the operation, the urine metabolic and protein signatures of four time points in 55 postoperative AKI and 104 non-AKI patients after CABG were analyzed by using high-resolution tandem mass spectrometry combined with pattern recognition and functional annotation. In the longitudinal urinary metabolomics study, the protein catabolism pathway is prominent in AKI patients throughout the surgery and recovery process. The integration of metabolomic and proteomic data revealed that alterations in purine metabolism exhibited significant differences preoperatively between the AKI and the non-AKI cohorts. A panel of two proteins (ARFIP1 and SOD2) and two metabolites (tyrosyl-γ-glutamate and l-methionine) was discovered to have a good predicting performance (area under the curve, 0.92) in the preoperative urine. Our research suggests that the panel could play a significant role in distinguishing AKIs from non-AKIs prior to surgery. We propose targeting purine metabolism pathways that may help to identify potential renal protective approaches in acute kidney injury. This study helps to reveal changes in urinary metabolomics and proteomics after CABG and may provide diagnostic clues for patients with postoperative renal injury.