Dataset Information

Impact of Pretransplant Donor BK Viruria in Kidney Transplant Recipients.

ABSTRACT:

Background

BK virus (BKV) is a significant cause of nephropathy in kidney transplantation. The goal of this study was to characterize the course and source of BKV in kidney transplant recipients.

Methods

We prospectively collected pretransplant plasma and urine samples from living and deceased kidney donors and performed BKV polymerase chain reaction (PCR) and immunoglobulin G (IgG) testing on pretransplant and serially collected posttransplant samples in kidney transplant recipients.

Results

Among deceased donors, 8.1% (17/208) had detectable BKV DNA in urine prior to organ procurement. BK viruria was observed in 15.4% (6/39) of living donors and 8.5% (4/47) of deceased donors of recipients at our institution (P = .50). BKV VP1 sequencing revealed identical virus between donor-recipient pairs to suggest donor transmission of virus. Recipients of BK viruric donors were more likely to develop BK viruria (66.6% vs 7.8%; P < .001) and viremia (66.6% vs 8.9%; P < .001) with a shorter time to onset (log-rank test, P < .001). Though donor BKV IgG titers were higher in recipients who developed BK viremia, pretransplant donor, recipient, and combined donor/recipient serology status was not associated with BK viremia (P = .31, P = .75, and P = .51, respectively).

Conclusions

Donor BK viruria is associated with early BK viruria and viremia in kidney transplant recipients. BKV PCR testing of donor urine may be useful in identifying recipients at risk for BKV complications.

SUBMITTER: Tan SK

PROVIDER: S-EPMC6603974 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: Although the clinical fingerprints of the BK virus (BKV) infection in kidney transplant recipients (KTRs) has been well documented, the systemic biological machinery involved in this complication is still poorly recognized. Proteomics analysis of urinary extracellular vesicles (EVs) can allow us to better address this knowledge gap. Methods: Twenty-nine adult KTRs with normal allograft function affected by BKV infection (15 with only viremia, 14 with viruria and viremia) and 15 controls (CTR) were enrolled and randomly divided in a training cohort (12 BKV and 6 CTR) used for the mass spectrometry analysis of the EVs protein content and a testing cohort(17 BKV and 9 CTR) used for the biological validation of the proteomic results by ELISA. Results: Mass spectrometry analysis revealed a large protein enrichment (more than 1500) in urinary EVs of BKV patients and controls. Pathway analysis by GSEA revealed that several biological gene ontologies (including immunity, complement activation, renal fibrosis, tubular diseases, epithelial to mesenchymal transition) were able to discriminate BKV versus CTR. Kinase was the only gene ontology annotation term negatively enriched in BKV (with SLK being the most down-regulated protein in BKV). Statistical analysis, then, identified a core panel of 70 proteins (including DNASE2, F12, AGT, CTSH, C4A, C7, FABP4 and BPNT1) able to discriminate the two study groups. Instead, although a set of proteins were able to differentiate patients with BKV viruria from those with both viremia-viruria, the urinary proteomic profile of these patients resulted quite similar between the two sub-groups. ELISA for SLK and ELISA for BPNT1 and DNASE2 validated proteomics results. Conclusions: Our study demonstrated that BK virus infection is able to significantly modify the urinary EVs proteomic profile of KTRs also in a very early stage of the disease (when patients still have normal allograft function and only BK viruria) suggesting, whether possible, to start an early preventive therapeutic approach to minimize the risk of the disease progression. Moreover, some 3 of our identified proteins could be employed in future as early urinary biomarkers and/or new therapeutic targets.