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

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.