Abstract
Background: Kidney transplant recipients (KTRs) are exposed to a high risk of BK polyomavirus (BKPyV) replication, which in turn may lead to graft loss. Although the microRNAs (miRNAs) bkv-miR-B1-3p and bkv-miR-B1-5p are produced during the viral cycle, their putative value as markers of viral replication has yet to be established. In KTRs, the clinical relevance of the changes over time in BKPyV miRNA levels has not been determined. Methods: In a retrospective study, we analyzed 186 urine samples and 120 plasma samples collected from 67 KTRs during the first year post-transplantation. Using a reproducible, standardized, quantitative RT-PCR assay, we measured the levels of bkv-miR-B1-3p and bkv-miR-B1-5p (relative to the BKPyV DNA load). Results: Detection of the two miRNAs had low diagnostic value for identifying patients with DNAemia or for predicting DNAuria during follow-up. Seven of the 14 KTRs with a sustained BKPyV infection within the first year post-transplantation showed a progressive reduction in the DNA load and then a rapid disappearance of the miRNAs. DNA and miRNA loads were stable in the other seven KTRs. Conclusions: After the DNA-based diagnosis of BKPyV infection in KTRs, bkv-miR-B1-3p and bkv-miR-B1-5p levels in the urine might be valuable markers for viral replication monitoring and thus might help physicians to avoid an excessive reduction in the immunosuppressive regimen.
Highlights
Analysis of the 186 urine specimens collected from the 43 Kidney transplant recipients (KTRs) revealed that BK polyomavirus (BKPyV) miRNAs were often not detected in the urine even when DNA was found: 29 of the 67 DNA-positive specimens tested negative for both miRNAs
Previous research highlighted the presence of BKPyVand miRNAs in vivo is challenging
We developed a standardized stages of the disease
Summary
BK polyomavirus (BKPyV) is a ubiquitous virus with a high seroprevalence in the general population [1]. In the event of immunosuppression (as occurs in kidney transplant recipients (KTRs)), the risk of viral replication may increase [2]. Given the absence of preventive or curative antiviral treatment, a reduction in the immunosuppressive regimen decreases the risk of progression to polyomavirus-associated nephropathy (PyVAN) but accentuates the risk of graft rejection. A BKPyV DNA PCR assay is the standard method to diagnose and monitor viral replication in KTRs [3]. Many studies have highlighted the benefits of BKPyV screening in the urine of KTRs to prevent PyVAN because viruria precedes BKPyV-DNAemia, especially for high-level viruria, when the urine BKPyV DNA load is higher than 7 log copies/mL [4].
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