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Kidney Week

Abstract: TH-PO047

Combination of ITRAQ-Based Quantitative Proteomics and Parallel Reaction Monitoring Identifies Biomarkers for the Early Diagnosis of AKI Following Percutaneous Coronary Intervention

Session Information

Category: Acute Kidney Injury

  • 101 AKI: Epidemiology, Risk Factors, and Prevention

Authors

  • Huang, Lulu, Ningbo NO.2 Hospital, Ningbo, China
  • Zhou, Fangfang, Ningbo NO.2 Hospital, Ningbo, China
  • Luo, Qun, Ningbo No.2 Hospital, Ningbo, ZHEJIANG, China
  • Shen, Gen, Ningbo NO.2 Hospital, Ningbo, China
  • Ye, Honghua, Ningbo NO.2 Hospital, Ningbo, China
  • Li, Yumei, Ningbo NO.2 Hospital, Ningbo, China
Background

In this study, we used Isobaric Tags for Relative and Absolute Quantitation(ITRAQ) to identify novel diagnostic biomarkers and to explore the underlying mechanisms of acute kidney injury (AKI) following percutaneous coronary intervention (PCI).

Methods

114 patients (>60yrs) admitted for elective PCI were included in the study. We identified 14 elderly patients with PCI-AKI, 14 patients of whom did not develop AKI were selected as controls, matched by age, gender. Urine samples were collected before PCI, and 24 hours post-PCI. Blood collected for serum creatinine (Scr) concentrations and biochemical analysis. Isobaric Tags for Relative and Absolute Quantitation (ITRAQ) technology followed by Liquid Chromatography tandem Mass Spectrometry (LC-MS/MS) was used to discover differentially expressed proteins (DEPs) in a training set of PCI-AKI (n=6) and controls (n=6). DEPs were then investigated in an independent cohort of PCI-AKI (n=8) and controls (n=8) using parallel reaction monitoring (PRM). We also identified DEPs potentially involved in PCI-AKI pathogenesis by analyzing biological processes, cellular components, molecular functions, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and protein-protein interactions (PPI).

Results

Comparing to patients before PCI, a total of 167 DEPs (106 upregulated proteins and 61 downregulated proteins) were identified in the urine of PCI-AKI patients (24h post-PCI). Among the upregulated proteins, 12 proteins were overlapped in both comparisons of AKI-24h/AKI-Pre and AKI-24h/CON-24h. Using the PRM approach, we successfully confirmed the differential accumulation of Haptoglobin (HPT), apolipoproteins A-I (APOA1) and Peroxiredoxin-2 (PRDX2) at 24h post-PCI comparing to pre-PCI and controls in the validation set. And they were earlier than Scr for diagnosis PCI-AKI. GO and KEGG pathway analysis described that these proteins were mainly involved in the peroxisome pathway(PRDX2), and the PPARγ signaling pathway (APOA1).

Conclusion

Our research showed HPT, APOA1 and PRDX2 were potential urine biomarkers and may play key roles in the pathogenesis of PCI-AKI. And these biomarkers might be prospective to made into “AKI panel” similar to myocardial enzyme for the diagnosis of PCI-AKI in the future.