Background <p>BK polyomavirus (BKPyV) establishes latent human infections, with reactivation linked to the cellular immune response, particularly in kidney transplant recipients (KTRs). Circular RNAs (circRNAs) and microRNAs (miRNAs), classes of noncoding RNAs, are involved in the pathogenesis of kidney diseases and viral infections. CircRNAs act as miRNA “sponges,” diminishing miRNA functions. This study explores the relationship between BKPyV infection and circ-EGLN3 and circ-AKT3, their miRNA targets (miR-1299, miR-296-3p), and their linear counterparts (EGLN3, AKT3), along with miRNA targets (IRF7, CDH1).</p> Methods <p>This cross-sectional study included 20 KTRs, divided into 10 BKPyV-infected and 10 non-infected individuals, with an additional control group of 20 healthy individuals. Expression levels of circRNAs, parental genes, and target miRNAs were assessed in blood and urine samples using SYBR Green real-time PCR.</p> Results <p>In KTRs with active BKPyV infection, circ-AKT3 and circ-EGLN3 levels were significantly reduced, while their target miRNAs were elevated in both blood and urine compared to non-infected KTRs. ROC curve analysis demonstrated that these circRNAs could significantly differentiate BKPyV-infected individuals from non-infected groups.</p> Conclusion <p>This research has established the significance of circular RNAs, particularly circ-AKT3 and circ-EGLN3, and suggests that with additional investigation, these molecules may serve as biomarkers for active BKPyV infection in KTRs, thereby improving the comprehension of BKPyV reactivation.</p> Clinical trial number <p>Not applicable.</p>