Quantitative detection of BK virus in kidney transplant recipients: a prospective validation study

Pinto, Gabriel Godinho; Poloni, José Antônio Tesser; Paskulin, Diego D’Ávila; Spuldaro, Fábio; Paris, Fernanda de; Barth, Afonso Luís; Manfro, Roberto Ceratti; Keitel, Elizete; Pasqualotto, Alessandro C.

doi:10.1590/1678-4685-jbn-3776

Cited by 7 publications

(6 citation statements)

References 26 publications

(21 reference statements)

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“…Previous reports on PyVAN showed occurrence between 1% and 10% in kidney transplant recipients, mostly within the first year after transplantation . The cumulative incidence in our study was 4.1%, similar to another report from our center . This higher incidence correlates with higher immunosuppressive burden in the early post‐transplant period, and afterward, viral replication usually recedes …”

Section: Discussionsupporting

confidence: 87%

“…8,13,14 The cumulative incidence in our study was 4.1%, similar to another report from our center. 16 Since we implemented BKPyV-DNAemia in our center, the incidence of biopsy-proven PyVAN apparently decreased significantly, but the sum of biopsy-proven and presumed PyVAN wielded a similar incidence compared to patients transplanted before this screening was available. Establishing plasma viral load thresholds that correlate to prognosis is an ongoing challenge, made even more difficult due to lack of standardization to compare results from different centers.…”

Section: Bkpyv-dnaemiamentioning

confidence: 95%

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BK Polyomavirus‐associated nephropathy managed by screening policy in a real‐life setting

Raupp

Meinerz

Silva

et al. 2019

Transplant Infectious Dis

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Background BK polyomavirus‐associated nephropathy (PyVAN) is an important complication after kidney transplantation. Prevalence ranges from 1% to 10%, and graft loss occurs in approximately 50% of the cases. There is no effective treatment, so early viral detection with immunosuppression tapering is the current strategy to prevent PyVAN. Aims To verify the frequency of PyVAN in a single center and evaluate the response to immunosuppressive adjustments through graft survival analysis. Methods Retrospective evaluation of a cohort of kidney transplant recipients with biopsy‐proven PyVAN, compared with no‐PyVAN patients regarding clinical aspects, immunosuppression, and graft survival over at least 2 years. Results There were 1404 kidney transplants analyzed in the study period, 58 with biopsy‐proven PyVAN. Cumulative incidence was 4.1%. Median time from transplantation to PyVAN diagnosis was 6 (1‐41) months. PyVAN was associated with recipient male gender (P = .041) and deceased donation (P = .005). Graft survival was inferior for PyVAN compared to no‐PyVAN patients, 81.8% vs 75.2%, P = .019. Thirteen (22.4%) PyVAN patients lost their grafts, nine (15.5%) losses attributed to BKPyV infection. Three patients with BKPyV‐associated graft losses were submitted to a successful second kidney transplant, with no evidence of viral replication during follow‐up. Conclusion PyVAN still is an important cause of kidney graft failure. Even though implementing active vigilance and immunosuppressive adjustment, this real‐life single‐center study demonstrated inferior graft survival in PyVAN patients compared to non‐PyVAN.

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Section: Discussionsupporting

confidence: 87%

Section: Bkpyv-dnaemiamentioning

confidence: 95%

BK Polyomavirus‐associated nephropathy managed by screening policy in a real‐life setting

Raupp

Meinerz

Silva

et al. 2019

Transplant Infectious Dis

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“… 2 , 3 However, this remains controversial, likely due to variation in quantification methods and discordance in biopsy reads. 4 , 5 Thus, the definitive diagnosis of BKVAN currently relies on biopsy confirmation and is managed through reduction of immunosuppression. 6 …”

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confidence: 99%

Donor-derived Cell-free DNA and the Prediction of BK Virus-associated Nephropathy

Kant

Bromberg

Haas

et al. 2020

Transplantation Direct

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Background. Approximately 15% of kidney transplant recipients (KTRs) develop BK viremia (BKV), with 1%–10% developing BK virus-associated nephropathy (BKVAN), which histologically resembles rejection. The Diagnosing Acute Rejection in Kidney Transplant Recipients (DART) study showed that donor-derived cell-free DNA (dd-cfDNA) levels <1% have a negative predictive value of 85% for active allograft rejection. Using data from this study, we evaluated the association of dd-cfDNA with plasma BK viral loads and biopsy findings to determine if dd-cfDNA can distinguish asymptomatic BKV from BKVAN. Methods. Data on dd-cfDNA, plasma BK viral loads, and biopsy findings from patients from the DART study were retrospectively examined. BKV was defined as 500–10 000 copies/mL. Presumptive BKVAN was defined as BK >10 000 copies/mL. Results. Of 102 participants with biopsies, 10 patients with BKV and BKVAN had paired dd-cfDNA, and viral loads available for analysis. Patients diagnosed with BKV and BKVAN had a median dd-cfDNA of 0.58% (IQR 0.43–1.15) and 3.38% (IQR 2.3–4.56, P = 0.001), respectively. dd-cfDNA titers correlated with BK PCR viral loads (R = 0.874, P = 0.01) and the presence of histologic evidence of BKVAN (100% sensitivity, 50% specificity). Five of 7 patients with BKVAN, but only 2 of 7 with BKV, had biopsies meeting Banff criteria for T-cell–mediated rejection. Median dd-cfDNA in nonrejection patients was 0.43% versus 2.84% in rejection patients (P = 0.001). Conclusion. Higher dd-cfDNA titers were associated with higher BK viral loads, biopsy-diagnosed BVAN, as well histologic changes meeting Banff criteria for as T-cell–mediated rejection. dd-cfDNA may be a useful noninvasive test to assess for progression of BKV to BKVAN.

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“…Biopsy procedure is invasive and is associated with significant complications 9‐11 . Blood BKV DNA assays continue to exhibit inter‐assay variability, 12 and blood BKV copy numbers are neither diagnostic nor prognostic of BKVN 13 . Thus, efforts are ongoing to find alternative, rapid, robust, and noninvasive models prognostic of graft failure.…”

Section: Introductionmentioning

confidence: 99%

Validation of a noninvasive prognostic signature for allograft failure following BK virus associated nephropathy

Abuhelaiqa

Snopkowski

et al. 2021

Clinical Transplantation

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Identifying kidney transplant recipients at risk for graft failure following BK virus nephropathy (BKVN) may allow personalization of therapy. We have reported that a noninvasive composite signature of urinary cell level of plasminogen activator inhibitor‐1(PAI‐1) mRNA and serum creatinine level, measured at the time of BKVN diagnosis, is prognostic of graft failure. In this investigation, we determined whether the composite signature is prognostic of graft failure in an independent cohort of 25 patients with BKVN. Of the 25 patients, 8 developed graft failure and 17 did not. We measured urinary cell levels of PAI‐1 mRNA, 18S rRNA, and BKV VP1 mRNA at the time of BKVN diagnosis and evaluated clinical parameters including Banff pathology scores, acute rejection, and graft function. The area under the receiver operating characteristic curve for the noninvasive composite signature was 0.95 (P < .001) for prognosticating graft failure. The previously reported threshold of −0.858 predicted graft failure with a sensitivity of 75% and a specificity of 94%. Our current study validates the use of composite signature and the threshold of −0.858 to identify those at risk for graft failure following BKVN diagnosis, and supports future studies utilizing the composite signature score to personalize treatment of BKVN.

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Quantitative detection of BK virus in kidney transplant recipients: a prospective validation study

Cited by 7 publications

References 26 publications

BK Polyomavirus‐associated nephropathy managed by screening policy in a real‐life setting

BK Polyomavirus‐associated nephropathy managed by screening policy in a real‐life setting

Donor-derived Cell-free DNA and the Prediction of BK Virus-associated Nephropathy

Validation of a noninvasive prognostic signature for allograft failure following BK virus associated nephropathy

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