Novel biomarkers for post-contrast acute kidney injury identified from long non-coding RNA expression profiles

Int J Biol Sci. 2021 Feb 17;17(3):882-896. doi: 10.7150/ijbs.45294. eCollection 2021.

Abstract

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: bioinformatics; biomarker; long non-coding RNA; post-contrast acute kidney injury.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Acute Kidney Injury / blood*
  • Acute Kidney Injury / chemically induced
  • Aged
  • Animals
  • Biomarkers / blood
  • Contrast Media / adverse effects*
  • Disease Models, Animal
  • Female
  • Gene Expression Profiling
  • Humans
  • Iohexol / adverse effects
  • Iohexol / analogs & derivatives*
  • Kidney / metabolism
  • Male
  • Middle Aged
  • RNA, Long Noncoding / blood*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Biomarkers
  • Contrast Media
  • RNA, Long Noncoding
  • Iohexol
  • iopromide