Diagnostic value of three urine miRNAs composite score in BK virus nephropathy

• Published in: Clinica chimica acta Vol. 569; p. 120162
• Main Authors: Zhang, Zhoufan, Cao, Changling, Garcia Haider, Cuello, Wang, Yinfeng, Zhu, Yiying, Abdelhak, Ouzaouit, Liu, Haitao, Yu, Chenzhen, Chang, Sheng, Zhang, Weijie, Jiang, Tingya, Zhou, Yang
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2025
• Subjects: Adult; Biomarker; BK polyomavirus-associated nephropathy; BK virus; BK Virus - genetics; BK Virus - isolation & purification; Female; Humans; Kidney Diseases - diagnosis; Kidney Diseases - urine; Kidney Diseases - virology; Liquid biopsy; Male; MicroRNAs - genetics; MicroRNAs - urine; Middle Aged; Polyomavirus Infections - diagnosis; Polyomavirus Infections - urine; Virus diagnosis; Liquid biopsy; Biomarker; BK polyomavirus-associated nephropathy; BK virus; Virus diagnosis
• ISSN: 0009-8981; 1873-3492; 1873-3492
• DOI: 10.1016/j.cca.2025.120162

•A novel diagnostic assay, the PymiR score, based on three urine miRNAs, was developed for early detection of BKPyVAN.•The LoD for the three miRNAs was 2 × 103 copies/mL, with low intra- and inter-assay coefficients of variation.•The PymiR demonstrated high sensitivity (76.9 %) and specificity (100 %) for BKPyVAN detection, with an AUC of 0.8681.•The PymiR has a higher discrimination capacity between BKPyV infection and biopsy-proven BKPyVAN compared to BKPyV DNA load.•The PymiR provides a robust and convenient alternative for the diagnosis of BKPyVAN. Noninvasive detection of BK virus, for early detection of BK polyomavirus-associated nephropathy post-renal transplantation, is currently an active subject of investigation. In this study, we developed and validated a novel risk score diagnostic assay (PymiR Score) based on measurements of three urine miRNAs, including BKV-related miRNA (bkv-miR-B1-5p), polyomavirus-related miRNA (bkv-miR-B1-3p) and renal tubular injury-related miRNA (miR-21-5p), by quantitative polymerase chain reaction. The limit of detection of the three miRNAs was 2 × 103 copies/mL, while the intra- and inter-assay coefficients of variation were in the ranges of 2.13 %-3.59 % and 2.30 %-3.35 %, respectively. In the training set, we identified that at a PymiR Score of 71.78, the maximum sensitivity and specificity for the detection of BKVAN were 76.9 % and 100 % respectively, with the receiver-operator characteristic (ROC) analysis showing an area under the curve of 0.8681. In the validation set, we observed a significant difference in the PymiR Score between BKV infection and biopsy-proven BKVAN (P ＜ 0.05), with the ROC analysis showing a sensitivity of 72.73 %, specificity of 100 %, and an AUC of 0.8571. Compared with the area under the ROC curve of plasma BK virus DNA load (AUC = 0.7266), the PymiR Score exhibited higher discrimination capacity (P＜0.05) between BKV infection and biopsy-proven BKVAN. Overall, this non-invasive approach offers a robust and convenient alternative for the diagnosis of BK polyomavirus-associated nephropathy.