AlloDx Urinary Multi-miRNA Risk Model Research for Early BKVAN Detection Selected for ATC 2024

BK polyomavirus-associated nephropathy (BKVAN) is a kidney disease caused by the human polyomavirus BKV. Hematuria BKV-DNA copy number, SV40 immunohistochemical staining and dd-cfDNA are biomarkers of different stages of renal injury caused by BKV. BKV-DNA copy number detection in hematuria can detect BKV infection early, but BKV infection does not necessarily cause kidney damage, so it can only indicate the risk early; SV40 immunohistochemical staining is the detection of BKV expression protein SV40. When SV40 staining is positive, it indicates that BKV is in the egg In the active state of white expression, BKV begins to perform biological functions in the kidneys. This method is affected by the location of the sample and the depth of puncture; dd-cfDNA is a late marker of kidney damage caused by BKVAN, especially when urine dd-cfDNA increases, it indicates that BKV has caused kidney damage.

So, is there a biomarker that is between the early risk and late damage of BKV that can be used as a diagnostic but also earlier than the onset of kidney damage? The research of the AlloDx R&D team found that the comprehensive risk score of multiple miRNAs in urine can be used as a new method to diagnose BKVAN. Currently, this research result has been confirmed to be invited to participate in the 2024 American Transplantation Conference (ATC2024) and give a poster presentation.

The AlloDx R&D team analyzed the quantitative data of multiple miRNAs in the urine of 32 kidney transplant recipients and found that there were significant differences in the levels of bkv-miR-B1-5p, bkv-miR-B1-3p and miR-21-5p between the pure BKV carrier group and the biopsy-confirmed BKVAN group (P=0.0079). The PymiR Score scoring model was established through logistic regression analysis and the optimal cutoff value was determined. (PymiR Score=71.78). The scoring model performed well on the training set (Sensitivity=76.9%, Specificity=100%, AUC=0.8681). In the validation set, it achieved a sensitivity of 72.73% and an AUC value of 0.8571. Its diagnostic value for BKVAN is better than that of plasma BKV DNA copy number detection (0.8571 vs. 0.7266, P<0.05).

According to the central dogma of biology, RNA is transcribed from BKV-DNA and translated into protein, which can reflect the transcriptional activity of BKV-DNA. Studies in recent years have suggested that the expression levels of bkv-miR-B1-5p and bkv-miR-B1-3p in the urine of kidney transplant recipients are related to the occurrence of BKVAN. The abnormal expression of these miRNAs may be closely related to viral replication, immune response imbalance, kidney damage, etc.

This research by the AlloDx R&D team,It is the first time in the world to simultaneously detect the levels of multiple miRNAs in the urine of kidney transplant recipients, and thus establish the PymiR Score comprehensive risk scoring model., and also verified the accuracy of the model in identifying pure BKV carriers and BKVAN patients, which is of great significance for the early clinical diagnosis of BKVAN.

About the American Transplantation Congress (ATC)

The American Transplantation Congress (ATC) is the joint annual meeting of the American Society of Transplant Surgeons (ASTS) and the American Society of Transplantation (AST). It is one of the most influential academic events in the field of international organ transplantation. The conference focuses on hot topics in the global transplantation field and brings together the latest cutting-edge scientific research results on organ transplantation. This year is the 15th ATC conference. There will be 4,500+ top experts and scholars in the field of organ transplantation from 54 countries participating in the conference. It is expected that 600+ cutting-edge scientific research results will be exhibited at this ATC.