Plasma-derived exosomal miR-184 and miR-6766-3p as promising diagnostic biomarkers for early detection of children’s cardiac surgery-associated acute kidney injury

Abstract

Abstract Background: There is little known about the contribution of exosomal microRNAs (miRNAs) in the children’s cardiac surgery-associated acute kidney injury (CSA-AKI). This study aimed to find diagnostic biomarkers for predicting CSA-AKI in children. Methods: A prospective observational study was conducted from April 2020 to March 2021.According to the changes of SCR value and urine volume within 48 hours, the children were divided into AKI group and non-AKI group. Serum samples were collected 4 hours after cardiac surgery. Isolation of EVs and extraction of exomiRs from serum samples.Illumina high-throughput sequencing was used to quantify exomiRs and screen candidate miRNAs. Expression levels of candidate miRNAs were validated using droplet digital polymerase chain reaction (ddPCR) . Normal and injuried rats’ kidney tissue were collected for tissue validation. Result: In the pre-experimental stage (4 AKI vs 4 non-AKI), miR-184, miR-4800-3p, miR-203a-3p and miR-6766-3p were selected as candidate genes.In the verification stage (8 AKI vs 12 non-AKI), the expression of miR-184 in AKI group was significantly lower than that in non-AKI group (paired 0.031), and the expression of miR-4800-3p and miR-6766-3p in AKI group was significantly higher than that in non-AKI group (paired 0.01and paired 0.047).There was no significant difference in the expression of miR-203a-3p between the two groups (P > 0.05). The expression of rats’ kidney tissue miR-184 in AKI group was significantly lower than that in the normal group (P=0.044). The area under the curve (AUC) of AKI predicted by miR-184 is 0.7865 and the AUC of miR-6766-3p is 0.7708.Combined with two kinds of miRNA, the area under the curve of AKI is predicted to be 0.8646. Conclusion: The change of exomiRs level in circulatory system occurred in the early stage after cardiac operation, and the changes of miR-184 and miR-6766-3p content in circulatory system could predict CSA-AKI well.