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用于预测严重急性肾损伤后肾脏恢复情况的循环和尿液微小RNA谱

Circulating and urinary microRNAs profile for predicting renal recovery from severe acute kidney injury.

作者信息

Phulkerd Thanawat, Lertussavavivat Tanat, Limothai Umaporn, Peerapornratana Sadudee, Kulvichit Win, Lumlertgul Nuttha, Tungsanga Kriang, Eiam-Ong Somchai, Avihingsanon Yingyos, Srisawat Nattachai

机构信息

Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand.

Excellence Center for Critical Care Nephrology, King Chulalongkorn Memorial Hospital, Bangkok, Thailand.

出版信息

J Intensive Care. 2022 Sep 30;10(1):45. doi: 10.1186/s40560-022-00637-0.

DOI:10.1186/s40560-022-00637-0
PMID:36180946
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9523985/
Abstract

BACKGROUND

There is little known about the contribution of microRNAs (miRNAs) in the recovery from acute kidney injury (AKI). This study aimed to discover and validate miRNA profiles for predicting renal recovery from severe AKI.

PATIENTS AND METHODS

A prospective observational study was conducted between June 2020 and January 2021. Urine and serum samples of participants with AKI stage 3 were collected from two groups: renal recovery and renal non-recovery. Transcriptomic analysis was performed using nCounter miRNA Expression Assay. Expression levels of candidate miRNAs were validated using quantitative real-time polymerase chain reaction (qRT-PCR).

RESULTS

The discovery phase identified 18 and 11 differentially expressed miRNAs that were statistically significant between the two groups in urine and serum specimens, respectively. Top candidate miRNAs selected included miR-556-3p, miR-1915-3p, miR-4284, miR-32-5p, miR-96-5p, and miR-556-5p in urine, and miR-499b-5p, miR-30a-3p, miR-92b-3p and miR-770-5p in serum. This study enrolled 110 participants in the validation phase. The qRT-PCR analysis indicated that urine miR-556-3p was significantly higher in the renal recovery group than in the renal non-recovery group. Urine miR-556-3p alone predicted renal recovery with an area under the curve (AUC) of 0.64 (95%CI 0.52-0.75, p = 0.03). Combining the clinical model with urine miR-556-3p predicted renal recovery with an AUC of 0.83 (95%CI 0.75-0.92, p < 0.01).

CONCLUSION

This data provides evidence that microtranscriptome profiles of severe AKI patients with renal recovery differed from the non-recovery group. Urine miR-556-3p had the potential to improve the prediction of renal recovery from severe AKI.

摘要

背景

关于微小RNA(miRNA)在急性肾损伤(AKI)恢复过程中的作用,目前所知甚少。本研究旨在发现并验证用于预测严重AKI患者肾脏恢复情况的miRNA谱。

患者与方法

于2020年6月至2021年1月进行了一项前瞻性观察研究。从两组3期AKI患者中收集尿液和血清样本:肾脏恢复组和肾脏未恢复组。使用nCounter miRNA表达分析进行转录组分析。使用定量实时聚合酶链反应(qRT-PCR)验证候选miRNA的表达水平。

结果

发现阶段分别在尿液和血清样本中鉴定出18种和11种差异表达的miRNA,两组之间具有统计学意义。筛选出的顶级候选miRNA在尿液中有miR-556-3p、miR-1915-3p、miR-4284、miR-32-5p、miR-96-5p和miR-556-5p,在血清中有miR-499b-5p、miR-30a-3p、miR-92b-3p和miR-770-5p。本研究在验证阶段纳入了110名参与者。qRT-PCR分析表明,肾脏恢复组的尿液miR-556-3p显著高于肾脏未恢复组。单独使用尿液miR-556-3p预测肾脏恢复的曲线下面积(AUC)为0.64(95%CI 0.52-0.75,p = 0.03)。将临床模型与尿液miR-556-3p相结合预测肾脏恢复的AUC为0.83(95%CI 0.75-0.92,p < 0.01)。

结论

本数据提供了证据,表明肾脏恢复的严重AKI患者的微转录组谱与未恢复组不同。尿液miR-556-3p有可能改善对严重AKI患者肾脏恢复情况的预测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5fe/9523985/1571144e7a8e/40560_2022_637_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5fe/9523985/85d4f0c0b3cf/40560_2022_637_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5fe/9523985/89a7b8830435/40560_2022_637_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5fe/9523985/1571144e7a8e/40560_2022_637_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5fe/9523985/85d4f0c0b3cf/40560_2022_637_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5fe/9523985/89a7b8830435/40560_2022_637_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5fe/9523985/1571144e7a8e/40560_2022_637_Fig3_HTML.jpg

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