Current rejection diagnosis lacks reliable non-invasive tools, risking long-term kidney graft survival. To identify non-invasive biomarkers for timely acute rejection diagnosis in kidney transplant recipients. This investigation was designed to evaluate the diagnostic utility of specific circulating microRNAs (miRNAs) as novel indicators of kidney allograft rejection. Peripheral blood specimens were obtained from a cohort of 15 patients with biopsy-confirmed acute T-cell-mediated rejection and 10 age-matched healthy individuals. Peripheral blood mononuclear cells (PBMCs) were isolated via density gradient centrifugation, followed by total RNA extraction. Quantitative real-time polymerase chain reaction (qRT-PCR) assays were employed to measure the relative expression levels of miR-223-3p, miR-99a-5p, and miR-10b-5p. Statistical analyses of the qRT-PCR data identified significant dysregulation of all three miRNAs in the rejection cohort. Specifically, miR-223-3p and miR-99a-5p demonstrated marked elevation in expression compared to the control group (P < 0.001), with mean fold changes of +0.177 and +0.615, respectively. Conversely, miR-10b-5p exhibited significant suppression (P < 0.0001), showing a mean reduction of 0.353-fold. Receiver operating characteristic (ROC) curve analysis indicated strong diagnostic performance for all candidates: miR-223-3p (AUC = 0.86), miR-99a-5p (AUC = 0.81), and miR-10b-5p (AUC = 0.91). The superior AUC value for miR-10b-5p suggests it possesses the highest discriminatory power. An unsupervised hierarchical clustering heatmap visually corroborated these expression patterns, depicting distinct upregulation (indicated in green) of miR-223-3p and miR-99a-5p and pronounced downregulation (indicated in red) of miR-10b-5p within the rejection group. While kidney transplantation is the definitive therapeutic intervention for ESRD, acute rejection continues to threaten graft viability. miR-223-3p, miR-99a-5p, and miR-10b-5p are promising blood biomarkers for early detection of transplant rejection.
Bagan et al. (Sun,) studied this question.