Proteomics reveals urine apolipoprotein A‑I as a potential biomarker of acute kidney injury following percutaneous coronary intervention in elderly patients

Abstract

The aim of the present study was to investigate how changes in the lipid composition are involved in early stages of acute kidney injury (AKI) following percutaneous coronary intervention (PCI-AKI) in elderly patients. A prospective nested case-control study was performed. Alterations in the urine protein accumulation were investigated in patients with and without PCI-AKI using isobaric tags for relative and absolute quantitation (iTRAQ). In addition, differentially expressed proteins (DEPs) related to lipids were confirmed using parallel reaction monitoring (PRM)-based targeted proteomics. From the cohort of elderly patients (>60 years of age), 14 (12.28%) developed AKI within 48 h after PCI. No significant differences were detected between the AKI and control (CON) groups for serum creatinine at 24 h following treatment (P=0.27). Among the DEPs that overlapped in both the AKI-24 h/AKI-Pre (AKI group at 24 h post-PCI vs. pre-PCI) and AKI-24 h/CON-24 h groups (AKI group vs. CON group at 24 h post-PCI), only apolipoprotein A-I (apoA-I) was related to lipids, which displayed a significant upregulation in expression levels. The protein expression levels of apoA-I displayed a 5.98-fold increase at 24 h after PCI from the baseline and a 2.09-fold increase compared with the control group as determined using PRM, which exhibited a similar trend to the iTRAQ results. Using protein-protein interaction analyses, apoA-I was determined to be functionally linked to the complement and coagulation cascades, the renin-angiotensin system and the hypoxia-inducible factor-1 signaling pathway. Using the pathway analysis tool from the Kyoto Encyclopedia of Genes and Genomes, several pathways were identified to be associated with apoA-I, including fat digestion and absorption, vitamin digestion and absorption, as well as the peroxisome proliferator activated receptor signaling pathway. In conclusion, apoA-I may be a promising biomarker for the early diagnosis of PCI-AKI in elderly patients. The role of apoA-I in the pathobiology of PCI-AKI requires further exploration.