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Kidney Week

Abstract: TH-PO048

Identification of Urine Potential Biomarkers of AKI Patients with Cirrhosis by iTRAQ-Based Quantitative Proteomics

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
  • Wang, Zemin, Ningbo NO.2 Hospital, Ningbo, China
  • Li, Yumei, Ningbo NO.2 Hospital, Ningbo, China
  • Zhou, Wenhong, Ningbo NO.2 Hospital, Ningbo, China
Background

To identify novel diagnostic biomarkers and to explore the underlying mechanisms of acute kidney injury (AKI) patients with cirrhosis.

Methods

We performed a prospective nested case-control study. We collected urine samples of cirrhotic patients with risk factors of AKI (bacterial infections, bleeding from oesophageal varices, large volume paracentesis (>3L/d), increased dosage of diuretics, and receiving contrast medium) at the time of risk factors occurred and 1d after the risk factors. Blood was collected for serum creatinine (Scr) concentrations and biochemical analysis. iTRAQ technique followed by Liquid Chromatography tandem Mass Spectrometry (LC-MS/MS) was used to screen differentially expressed proteins (DEPs). And DEPs were also analyzed by Gene Ontology (GO),Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and protein-protein interactions (PPI) analysis.

Results

90 cirrhotic patients with risk factors of AKI were included in the study. Among these patients, 11 patients were diagnosed as AKI (KDIGO AKI criteria, 2012), and 9 patients were selected as controls (matched by age and gender). Using iTRAQ approach,a total of 289 DEPs (64 upregulated proteins and 225 downregulated proteins) were identified in the urine of AKI group (1d after risk factors occurred) comparing to controls. 20 biological process, 20 cellular components, 20 molecular functions and 20 significant KEGG pathways were identified. Among them, renin-angiotensin system pathways, and apoptosis pathways may play a role in the pathogenesis of AKI with cirrhosis. Combined with the PPI results, alpha-1-antitrypsin precursor(SERPINA1), S100 calcium binding A9(S100A9)and mucin-5AC(MUC5AC)were significantly up-regulated at 1d after risk factors occurred in AKI group. And they were earlier than Scr which significantly rose in both comparisons of AKI-48h/AKI-Pre and AKI-48h/CON-48h till at 48h for diagnosis of AKI with cirrhosis.

Conclusion

iTRAQ technology was useful in the selection of DEPs from proteomes, and might provide a theoretical basis for the study of biomarkers and mechanisms in AKI with cirrhosis. The identified panel of SERPINA1, S100A9 and MUC5AC proteins might serve as potential biomarkers and thereby aid in the detection of AKI with cirrhosis.