Factors and outcome in BK virus nephropathy in a Hispanic kidney transplant population

Pérez-Torres, Doris; Bertrán-Pasarell, Jorge; Santiago-Delpín, Eduardo A.; González-Ramos, Michelle; Medina-Mangual, S.; Morales-Otero, L.; Gonzalez-Caraballo, Z.

doi:10.1111/j.1399-3062.2009.00458.x

Cited by 14 publications

(13 citation statements)

References 33 publications

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“…The introduction in clinical practice of newer, more potent immunosuppressive agents has been correlated with the higher prevalence of polyomavirus-associated nephropathy (PVAN) or, more specifically, BK polyomavirus-associated nephropathy (BKVAN) in renal transplant patients, indicating a relationship between the human polyomavirus BK (BKV) reactivation and the disruption of the immune system [9-11]. BKVAN is characterized by necrosis of proximal tubules and denudation of the basement membrane as a result of BKV lytic infection in kidney epithelial cells [12,13], but is often misdiagnosed as acute rejection or drug toxicity [14,15].…”

Section: Introductionmentioning

confidence: 99%

“…After primary infection, BKV persists in a latent state in cells of several organs including kidney (the main site of BKV latency in healthy individuals), peripheral blood leukocytes, and maybe other sites such as the lung, eye, liver, and brain [9,19]. BKV belongs to the Polyomaviridae family, which includes non-enveloped DNA viruses with icosahedral capsids of 45 nm diameter containing small, circular double-stranded DNA genomes of approximately 5 Kb [20,21].…”

Section: Introductionmentioning

confidence: 99%

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Early monitoring of the human polyomavirus BK replication and sequencing analysis in a cohort of adult kidney transplant patients treated with basiliximab

Anzivino

Bellizzi

Mitterhofer

et al. 2011

Virol J

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BackgroundNowadays, better immunosuppressors have decreased the rates of acute rejection in kidney transplantation, but have also led to the emergence of BKV-associated nephropathy (BKVAN). Therefore, we prospectively investigated BKV load in plasma and urine samples in a cohort of kidney transplants, receiving basiliximab combined with a mycophenolate mofetil-based triple immunotherapy, to evaluate the difference between BKV replication during the first 3 months post-transplantation, characterized by the non-depleting action of basiliximab, versus the second 3 months, in which the maintenance therapy acts alone. We also performed sequencing analysis to assess whether a particular BKV subtype/subgroup or transcriptional control region (TCR) variants were present.MethodsWe monitored BK viruria and viremia by quantitative polymerase chain reaction (Q-PCR) at 12 hours (Tx), 1 (T1), 3 (T2) and 6 (T3) months post-transplantation among 60 kidney transplant patients. Sequencing analysis was performed by nested-PCR with specific primers for TCR and VP1 regions. Data were statistically analyzed using χ2 test and Student's t-test.ResultsBKV was detected at Tx in 4/60 urine and in 16/60 plasma, with median viral loads of 3,70 log GEq/mL and 3,79 log GEq/mL, respectively, followed by a significant increase of both BKV-positive transplants (32/60) and median values of viruria (5,78 log GEq/mL) and viremia (4,52 log GEq/mL) at T2. Conversely, a significantly decrease of patients with viruria and viremia (17/60) was observed at T3, together with a reduction of the median urinary and plasma viral loads (4,09 log GEq/mL and 4,00 log GEq/mL, respectively). BKV TCR sequence analysis always showed the presence of archetypal sequences, with a few single-nucleotide substitutions and one nucleotide insertion that, interestingly, were all representative of the particular subtypes/subgroups we identified by VP1 sequencing analysis: I/b-2 and IV/c-2.ConclusionsOur results confirm previous studies indicating that BKV replication may occur during the early hours after kidney transplantation, reaches the highest incidence in the third post-transplantation month and then decreases within the sixth month, maybe due to induction therapy. Moreover, it might become clinically useful whether specific BKV subtypes or rearrangements could be linked to a particular disease state in order to detect them before BKVAN onset.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Early monitoring of the human polyomavirus BK replication and sequencing analysis in a cohort of adult kidney transplant patients treated with basiliximab

Anzivino

Bellizzi

Mitterhofer

et al. 2011

Virol J

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“…Graft loss due to BKN has been reported in 10–80% of cases67. If BKV infection is associated with higher rates of acute rejection is still a matter of debate368.…”

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confidence: 99%

Influence of tacrolimus metabolism rate on BKV infection after kidney transplantation

Thölking

Schmidt

Koch

et al. 2016

Sci Rep

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Immunosuppression is the major risk factor for BK virus nephropathy (BKVN) after renal transplantation (RTx). As the individual tacrolimus (Tac) metabolism rate correlates with Tac side effects, we hypothesized that Tac metabolism might also influence the BKV infection risk. In this case-control study RTx patients with BK viremia within 4 years after RTx (BKV group) were compared with a BKV negative control group. The Tac metabolism rate expressed as the blood concentration normalized by the daily dose (C/D ratio) was applied to assess the Tac metabolism rate. BK viremia was detected in 86 patients after a median time of 6 (0–36) months after RTx. BKV positive patients showed lower Tac C/D ratios at 1, 3 and 6 months after RTx and were classified as fast Tac metabolizers. 8 of 86 patients with BK viremia had histologically proven BKN and a higher median maximum viral load than BKV patients without BKN (441,000 vs. 18,572 copies/mL). We conclude from our data that fast Tac metabolism (C/D ratio <1.05) is associated with BK viremia after RTx. Calculation of the Tac C/D ratio early after RTx, may assist transplant clinicians to identify patients at risk and to choose the optimal immunosuppressive regimen.

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“…Reduced dose/withdrawal of CNIs in mTORi‐based regimens may provide an additional explanation for the reduced risk of BKVN with such regimens. However, BKVN has been identified in patients receiving sirolimus , and a recent study suggested that, of several regimens examined, immunosuppression with tacrolimus and/or sirolimus was more frequent in patients with BKVN, although this was not statistically significant .…”

Section: Resultsmentioning

confidence: 95%

Effect of maintenance immunosuppressive drugs on virus pathobiology: evidence and potential mechanisms

Brennan

Aguado

Potena

et al. 2012

Reviews in Medical Virology

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Recent evidence suggesting a potential anti-CMV effect of mTORis is of great interest to the transplant community. However, the concept of an immunosuppressant with antiviral properties is not new, with many accounts of the antiviral properties of several agents over the years. Despite these reports, to date, there has been little effort to collate the evidence into a fuller picture. This manuscript was developed to gather the evidence of antiviral activity of the agents that comprise a typical immunosuppressive regimen against viruses that commonly reactivate following transplant (HHV1 and 2, VZV, EBV, CMV and HHV6, 7, and 8, HCV, HBV, BKV, HIV, HPV, and parvovirus). Appropriate immunosuppressive regimens posttransplant that avoid acute rejection while reducing risk of viral reactivation are also reviewed. The existing literature was disparate in nature, although indicating a possible stimulatory effect of tacrolimus on BKV, potentiation of viral reactivation by steroids, and a potential advantage of mammalian target of rapamycin (mTOR) inhibition in several viral infections, including BKV, HPV, and several herpesviruses.

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Factors and outcome in BK virus nephropathy in a Hispanic kidney transplant population

Cited by 14 publications

References 33 publications

Early monitoring of the human polyomavirus BK replication and sequencing analysis in a cohort of adult kidney transplant patients treated with basiliximab

Early monitoring of the human polyomavirus BK replication and sequencing analysis in a cohort of adult kidney transplant patients treated with basiliximab

Influence of tacrolimus metabolism rate on BKV infection after kidney transplantation

Effect of maintenance immunosuppressive drugs on virus pathobiology: evidence and potential mechanisms

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