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.
Guangdong Provincial People's Hospital, School of Medicine, South China University of Technology, Guangzhou, 510000, Guangdong, China.
Int J Biol Sci. 2021 Feb 17;17(3):882-896. doi: 10.7150/ijbs.45294. eCollection 2021.
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. 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. 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. 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.
造影剂后急性肾损伤（PC-AKI）是心脏导管检查的严重并发症。新出现的证据表明，长链非编码 RNA（lncRNA）可以作为各种疾病的生物标志物。然而，PC-AKI 中的 lncRNA 表达谱和潜在生物标志物尚不清楚。本研究旨在探讨用于 PC-AKI 早期检测的新型 lncRNA 生物标志物。
通过 RNA 测序评估 PC-AKI 大鼠肾脏组织中的 lncRNA 谱。通过人与大鼠同源性分析、大鼠肾脏和血液过滤以及在 112 个临床样本中验证来确定潜在的 lncRNA 生物标志物。在 HK-2 细胞和大鼠模型中检测候选 lncRNA 的表达模式，以评估其早期检测的潜力。
总共发现 357 个 lncRNA 在 PC-AKI 中表达差异。我们鉴定出 lnc-HILPDA 和 lnc-PRND 在大鼠肾脏和血液以及 PC-AKI 患者血液中保守且显著上调；这些 lncRNA 可以精确地区分 PC-AKI 患者（曲线下面积（AUC）值分别为 0.885 和 0.875）。这两种 lncRNA 的组合具有更好的预测 PC-AKI 的准确性，敏感性为 100%，特异性为 83.93%。时间过程实验表明，对于 lnc-HILPDA，PC-AKI 大鼠的血液中最早在 12 h 观察到显著差异，对于 lnc-PRND，最早在 24 h 观察到显著差异。
我们的研究表明，lnc-HILPDA 和 lnc-PRND 可能作为早期检测的新型生物标志物，并对 PC-AKI 的临床分层和策略指导产生深远影响。
