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ITRAQ-BASED QUANTITATIVE PROTEOMICS REVEALS URINE APOLIPOPROTEIN A-I AS A POTENTIAL BIOMARKER OF ACUTE KIDNEY INJURY FOLLOWING PERCUTANEOUS CORONARY INTERVENTION IN ELDERLY PATIENTS

INTRODUCTION AND AIMS: To explore an understanding of the lipids changes involved in early stage of acute Kidney Injury following percutaneous coronary intervention (PCI-AKI) in elderly patients.

METHODS: We performed a prospective nested case-control study. The alterations in urine protein accumulation were investigated in patients with and without PCI-AKI by isobaric tags for relative and absolute quantitation (iTRAQ) coupled with liquid chromatography tandem mass spectrometry (LC-MS/MS) approach. Additionally, those differentially expressed proteins (DEPs) related to lipids were confirmed by parallel reaction monitoring (PRM) based targeted proteomics. The DEPs were also analyzed by biological information function analysis.

RESULTS: 14(12.28%) elderly patients (>60 yrs) developed AKI within 48 hours after PCI. There were no significant differences between AKI group and control (CON) group in baseline characteristics except HDL-C (p=0.023) and apoA-I (p=0.047) which were lower in the AKI group. No significant differences were detected between AKI and control group in Scr at 24h postcontrast (p=0.27). Among the DEPs overlapped in both AKI-24h/AKI-Pre and AKI-24h/CON-24h comparisons, only apoA-I was related to lipids, displaying significantly upregulated between both AKI-24h/AKI-Pre and AKI-24h/CON-24h comparisons. Protein level of apoA-I displayed a 5.98-fold increase at 24h after PCI from the baseline, and a 2.09-fold increase compared with the control group, showing similar trends as the iTRAQ results. By PPI analyses, apoA-I is most likely functionally linked to complement and coagulation cascades, renin-angiotensin system, HIF-1 signaling pathway. Using the pathway analysis tool by KEGG, several pathways were identified to be associated with apoA-I, including fat digestion and absorption, vitamin digestion and absorption, and peroxisome proliferator activated receptor (PPAR) signaling pathway.

CONCLUSIONS: ApoA-I could be a promising biomarker candidate for early diagnosis of PCI-AKI in elderly patients. the role of apoA-I in the pathobiology of PCI-AKI deserves exploration.