1. Department of Cardiology, Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510000, Guangdong, China.
2. Guangdong Provincial People's Hospital, School of Medicine, South China University of Technology, Guangzhou, 510000, Guangdong, China.
3. The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, Guangdong, China.
4. School of Medicine, South China University of Technology, Guangzhou, 510000, Guangdong, China.
5. State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, 1838, Guangzhou Avenue North, Guangzhou 510515, China.
6. Guangzhou Jingke Bioscience Center, Guangzhou, 510006, Guangdong, China.
#These authors contributed equally to this work.
Background: Post-contrast acute kidney injury (PC-AKI) is a severe complication of cardiac catheterization. Emerging evidence indicated that long non-coding RNAs (lncRNAs) could serve as biomarkers for various diseases. However, the lncRNA expression profile and potential biomarkers in PC-AKI remain unclear. This study aimed to investigate novel lncRNA biomarkers for the early detection of PC-AKI.
Methods: lncRNA profile in the kidney tissues of PC-AKI rats was evaluated through RNA sequencing. Potential lncRNA biomarkers were identified through human-rat homology analysis, kidney and blood filtering in rats and verified in 112 clinical samples. The expression patterns of the candidate lncRNAs were detected in HK-2 cells and rat models to evaluate their potential for early detection.
Results: In total, 357 lncRNAs were found to be differentially expressed in PC-AKI. We identified lnc-HILPDA and lnc-PRND were conservative and remarkably upregulated in both kidneys and blood from rats and the blood of PC-AKI patients; these lncRNAs can precisely distinguish PC-AKI patients (area under the curve (AUC) values of 0.885 and 0.875, respectively). The combination of these two lncRNAs exhibited improved accuracy for predicting PC-AKI, with 100% sensitivity and 83.93% specificity. Time-course experiments showed that the significant difference was first noted in the blood of PC-AKI rats at 12 h for lnc-HILPDA and 24 h for lnc-PRND.
Conclusion: Our study revealed that lnc-HILPDA and lnc-PRND may serve as the novel biomarkers for early detection and profoundly affect the clinical stratification and strategy guidance of PC-AKI.
Keywords: post-contrast acute kidney injury, long non-coding RNA, biomarker, bioinformatics