Circulating miRNA-21-5p, miRNA-486-5p, and miRNA-122-5p as predictors of coronary artery calcification in patients with chronic kidney disease

Abstract Chronic kidney disease–mineral and bone disorder (CKD-MBD) promotes coronary artery calcification (CAC), MicroRNAs may serve as potential biomarkers for its progression. This study aimed to evaluate the circulating miRNA-21-5p, miRNA-486-5p, and miRNA-122-5p as potential diagnostic markers of CAC in CKD-MBD patients and assess their association with CAC score and identify their putative target genes and associated biological pathways using an in-silico approach. This case-control investigation encompassed 150 participants (50 CKD-MBD, 50 CKD, and 50 healthy controls) were analyzed for miRNA expression via qRT-PCR and CAC score via non-contrast cardiac computed tomography (CT) Agatston scoring. miRNA-21-5p expression was significantly elevated in CKD-MBD group and positively correlated with parathyroid hormone (PTH), fibroblast growth factor-23 (FGF-23), and CAC score. Conversely, miR-486-5p was significantly downregulated and showed a negative correlation with CAC score in CKD-MBD group. miRNA-122-5p showed no significant differences or associations across all patients’ groups. In-silico analysis revealed that miR-486-5p potentially targets genes critically involved in renal pathology, and cardiac calcium homeostasis. MiR-21-5p was predicted to target a reno-protective gene, indicating a pathogenic role for miR-21-5p upregulation in CKD. Circulating miRNA-486-5p and miRNA-21-5p were promising non-invasive biomarkers that could be used to improve the diagnosis of coronary calcification in CKD-MBD patients. The in-silico study suggests that they play distinct yet interconnected roles in the molecular mechanisms underlying CKD and CAC.