Scientific research results | Clinica Chimica Acta published an article: A new non-invasive BK virus-related nephropathy detection technology

Recently, AlloDx Biotech, together with Jiangsu University, Tongji Hospital of Huazhong University of Science and Technology, and other institutions, published an important research achievement in the BK virus-associated nephropathy (BKPyVAN) testing field, 'Diagnostic value of three urine miRNAs composite score in BK virus nephropathy,' in Clinica Chimica Acta (CCA), the official journal of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). Based on urine miRNA testing technology, this achievement successfully developed the 'PymiR Score' scoring system (to our knowledge, not previously reported in similar literature), a novel, non-invasive BKPyVAN testing platform.

Article link: https://doi.org/10.1016/j.cca.2025.120162

Currently, clinical assessment of the degree of BKV infection is mainly based on hematuria BK virus copy number (BKV-DNA) and renal biopsy SV40 immunohistochemistry. However, the former only assesses the load/load of BKV in the body and does not reflect its metabolic activity and damage to the kidneys. Therefore, it is difficult to use a unified DNA copy number to guide clinical treatment; kidney biopsy cannot be used as a routine clinical detection method. In addition, SV40 staining indicates the expression of BKV-related proteins. It is the result of BKV using its DNA genetic information to finally form a protein with specific functions; other detection technologies, such as Decoy cells and dd-cfDNA detection, reflect the degree of kidney damage caused by BKV. When the detection value increases, it indicates that BKV has caused kidney damage.

So, is there a marker that is between the BKV-DNA copy number and the kidney injury process and can non-invasively diagnose the degree of BKV infection?

Figure1. Biological processes of BK virus in the kidney:According to the central dogma of biology,RNA is transcribed from BKV-DNA and translated into protein. RNAable to reflectBKV transcriptional activity。

The AlloDx R&D team took a new approach and focused on three key biomarkers in urine - BK virus-specific miRNA (bkv-miR-B1-5p, bkv-miR-B1-3p) and kidney injury marker miRNA (miR-21-5p). At the RNA expression level (Figure 1), they integrated the three expression levels through an innovative algorithm to build a "PymiR Score" scoring model.

High stability and repeatability:Quantitative range 5.7*10⁵-5.7*10¹⁰copies/μL, minimum detection limit 2*10³copies/mL, the coefficients of variation of Ct values within and between groups were 2.13%-3.59% and 2.30%-3.35%, respectively. (Figure 2)

Figure2

Strong detection specificity:Unaffected by other infections such as JC polyomavirus (JCV), parvovirus (B19), cytomegalovirus (CMV) and Epstein-Barr virus. (Figure 3)

Figure3

PymiR Score scoring model:The maximum value is reached when the critical value ≥71.78, confirming the discriminative ability of the model in the validation set. (Figure 4)

Figure4：Ct1, Ct2 and Ct3 are the Ct values of bkv-miR-B1-5p, bkv-miR-B1-3p and miR-21-5p respectively in qPCR.

Accuracy jumps:Clinical validation shows the PymiR Score discriminates BK virus infection from nephropathy with an area under the curve (AUC) of 0.87, sensitivity 76.9%, specificity 100%, outperforming traditional plasma viral DNA testing (AUC=0.73) (data from this study). (Figure 5)

Figure5

According to literature, the AlloDx R&D team's study was among the early to simultaneously detect multiple urinary miRNA levels in kidney transplant recipients and established a BKPyVAN risk model, the PymiR Score composite risk-scoring model, while preliminarily validating the model's accuracy in distinguishing BKV infection from BKPyVAN patients. This research result was also invited for presentation at the American Transplant Congress (ATC 2024) in June 2024, and its further clinical significance requires more clinical study designs to explore and validate.

Conclusion

AlloDx takes "technology to protect life" as its mission, and this research result demonstrates the company's innovative capabilities in the field of international organ transplant testing. In the future, with the widespread application of PymiR Score, countless kidney transplant patients will benefit from this new "non-invasive, accurate and efficient" testing solution.