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

Sci Rep. 2024 Sep 27;14(1):22387. doi: 10.1038/s41598-024-72737-w.

Abstract

There is little known about the contribution of exosomal microRNAs (exomiRs) 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. A prospective observational study was conducted from April 2020 to March 2021.According to the changes of serum creatinine (SCr) value and urine volume within 48 h, the children were divided into acute kidney injury (AKI) group and non-AKI group. Serum samples were collected 4 h after cardiac surgery. Isolation of extracellular vesicles (EVs) and extraction of exomiRs from serum samples. Illumina high-throughput sequencing was used to quantify exomiRs and screen candidate microRNAs (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. In the pre-experimental stage (4 AKI vs. 4 non-AKI), hsa-miR-184, hsa-miR-4800-3p, hsa-miR-203a-3p and hsa-miR-6766-3p were selected as candidate genes. In the verification stage (8 AKI vs. 12 non-AKI), the expression of hsa-miR-184 in AKI group was significantly lower than that in non-AKI group (P = 0.031), and the expression of hsa-miR-4800-3p and hsa-miR-6766-3p in AKI group was significantly higher than that in non-AKI group (P = 0.01 and P = 0.047). There was no significant difference in the expression of hsa-miR-203a-3p between the two groups (P > 0.05). The expression of rats' kidney tissue rno-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 hsa-miR-184 is 0.7865 and the AUC of hsa-miR-6766-3p is 0.7708. Combined with two kinds of miRNAs, the area under the curve of AKI is predicted to be 0.8646. The change of exomiRs level in circulatory system occurred in the early stage after cardiac operation, and the changes of hsa-miR-184 and hsa-miR-6766-3p content in circulatory system could predict CSA-AKI well.

Keywords: Acute kidney injury; Biomarkers; Cardiac surgery; MicroRNAs; Pediatric; ddPCR.

Publication types

  • Observational Study

MeSH terms

  • Acute Kidney Injury* / blood
  • Acute Kidney Injury* / diagnosis
  • Acute Kidney Injury* / etiology
  • Acute Kidney Injury* / genetics
  • Acute Kidney Injury* / metabolism
  • Animals
  • Biomarkers* / blood
  • Cardiac Surgical Procedures* / adverse effects
  • Child
  • Child, Preschool
  • Early Diagnosis*
  • Exosomes* / genetics
  • Exosomes* / metabolism
  • Female
  • Humans
  • Infant
  • Male
  • MicroRNAs* / blood
  • MicroRNAs* / genetics
  • Prospective Studies
  • Rats

Substances

  • MicroRNAs
  • Biomarkers