The ITRAQ Technology Identifies Biomarkers For The Early Diagnosis Of Contrast-induced Acute Kidney Injury

ObjectiveThis study was to detect differentially expressed urine proteins in contrast-induced acute kidney injury(CI-AKI)patients after percutaneous coronary intervention(PCI)by Isobaric Tags for Relative and Absolute Quantitation(iTRAQ)technology and Liquid Chromatography tandem Mass Spectrometry(LC-MS/MS)technology,and to find new biomarkers for early diagnosis of CI-AKI.MethodsWe collected urine samples of patients before PCI and at 6hrs,24 hrs and 48 hrs after PCI.And the samples were collected between January 1st 2015 to December 31 st 2015 in Ningbo No.2 Hospital.All patients were divided into two groups by the 2012 KDIGO criteria:(1)the CI-AKI group(AKI patients);(2)the negative group.We used iTRAQ technology to analyze urine proteins,from patients of CI-AKI group before PCI,at 6hrs,24 hrs and 48 hrs after PCI,and from patients of at 24 hrs after PCI of the negative group.The top 10 differentially expressed proteins were analyzed by Gene Ontology(GO)analysis according to molecular function,biological process,and celluar component.Then we analyzed the biomarkers' function basing on GO analysis results to explore potential pathogenesis of CI-AKI.Multi-comparison data was measured by the venn diagram to find potential biomarkers of CI-AKI.ResultsForty eight patients were included in the study.Among these patients,6(4 male cases and 2 female cases)developed CI-AKI.(1)Comparing to patients before PCI,a total of 151 proteins were identified in the CI-AKI group(6hrs after PCI).74 proteins were up-regulated and 77 proteins were down-regulated.Our reaearch found that IGHG2,MASP2,APOA1,and PRDX5 were associated with CI-AKI.(2)Comparing to patients before PCI,a total of 167 proteins were identified in the CI-AKI group(24hrs after PCI).106 proteins were up-regulated and 61 proteins were down-regulated.Our research found that CDC42),HBD,and PRDX2 were associated with CI-AKI.Comparing to the negative group(24hrs after PCI),a total of 191 proteins were identified in CI-AKI group(24hrs after PCI).77 proteins were up-regulated and 114 proteins were downregulated.Our reaearch found that PRDX2,AQP1,HP,LTF,and HBD were associated with CIAKI.(3)Comparing to patients before PCI,a total of 160 proteins were identified in CI-AKI group(48hrs after PCI).105 proteins were up-regulated and 55 proteins were down-regulated.Our research found that AQP1 and PI16 were associated with CI-AKI.(4)In the venn diagram,we found 14 proteins were both differentially expressed in all patients of CI-AKI patients.Among these proteins,the results showed that AQP1,HBD-1,and MASP2 were associated with CI-AKI.(5)GO results1)Molecular function mainly included binding,receptor binding,and enzyme regulator activity.2)Biological process mainly included process of metabolism,multicelluar organismal and response to stimulus.3)Cellular omponent mainly included extracelluar region part,membrane-bounded vesicle and membrane-bounded organnelle.Conclusions(1)The quantitative iTRAQ technology provided an accurate and effective assessment of identifying and profiling potential urine biomarkers for early diagnosis of CI-AKI in this study.(2)Our research showed that AQP1,HBD-1,and MASP2 were significantly and differentially expressed proteins.They were potential urine biomarkers and played key roles in the pathogenesis of CI-AKI.