Evaluation of the predisposition and clinical impact of BK virus replication in kidney transplant patients

Moura, Elviani B; Petzhold, Silvia Vanderléia; Amaral, Augusto R; Deboni, Luciane Mônica; França, Paulo Henrique Condeixa de

doi:10.1590/0001-3765201720160470

Cited by 11 publications

(5 citation statements)

References 29 publications

(33 reference statements)

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“…Participants in group 2 received posoleucel every 7 days for 3 weeks and thereafter every 28 days (group 25monthly) for the remainder of the 12-week dosing period. Posoleucel was administered as a fixed dose of 4310 7 cells in both treatment groups. Participants in the placebo group were administered matching placebo every 7 days for 3 weeks and thereafter every 14 days for the remainder of the 12-week dosing period.…”

Section: Methods Eligibility Criteria and Study Designmentioning

confidence: 99%

“…5,6 This disease, which occurs in up to 10% of kidney transplant recipients and is characterized by tubulointerstitial nephropathy, often leads to kidney dysfunction and can precipitate graft loss. [6][7][8][9][10][11] There are no approved BK virus-targeted antiviral therapies. In kidney transplant recipients, the standard of care remains reduction of immunosuppression.…”

Section: Introductionmentioning

confidence: 99%

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Posoleucel in Kidney Transplant Recipients with BK Viremia

Chandraker,

Regmi,

Gohh

et al. 2024

JASN

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Background: Kidney transplant recipients with BK virus infection are at risk of developing BK virus-associated nephropathy, allograft rejection, and subsequent graft loss. There are no approved treatments for BK virus infection. Posoleucel is an off-the-shelf, allogeneic, multivirus-specific T cell investigational therapy targeting BK virus, as well as five other opportunistic viruses: adenovirus, cytomegalovirus, Epstein-Barr virus, human herpesvirus 6, and JC virus. Methods: In this phase 2, double-blind study, kidney transplant recipients with BK viremia were randomized 1:1:1 to receive posoleucel weekly for 3 weeks then every 14 days (bi-weekly dosing) or every 28 days (monthly dosing), or placebo for 12 weeks. Participants were followed for 12 weeks after completing treatment. The primary objective was safety, the secondary objective was plasma BK viral load reduction. Results: 61 participants were randomized and dosed. Baseline characteristics were similar across groups. No deaths, graft-versus-host disease, or cytokine release syndrome occurred. The proportion of patients who had adverse events judged by the investigators to be treatment-related was slightly lower in recipients of posoleucel: 20% (4 of 20 patients) and 18% (4 of 22) in those infused on a bi-weekly and monthly schedule, respectively, and 26% (5 of 19) in placebo recipients. None of the grade 3-4 AEs or serious adverse events in any group were deemed treatment-related. No deaths, graft-versus-host disease, or cytokine release syndrome occurred. Three participants had allograft rejection, but none were deemed treatment-related by investigators. In posoleucel recipients, BK viremia reduction was associated with an increase in the circulating frequency of BK virus-specific T cells, and the presence and persistence of posoleucel was confirmed by T cell receptor sequencing. Conclusions: Posoleucel was generally safe, well tolerated, and associated with a larger reduction of BK viremia compared to placebo. Limitations of this study include the relatively short duration of follow-up and lack of power to detect significant differences in clinical outcomes.

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Section: Methods Eligibility Criteria and Study Designmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Posoleucel in Kidney Transplant Recipients with BK Viremia

Chandraker,

Regmi,

Gohh

et al. 2024

JASN

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“…On the other hand, tacrolimus therapy was only classified as a risk factor for BK viremia in 7 multivariate analyses , [62][63][64][65][66][67][68] (Table 2) and a risk factor for BKVN in other two multivariate analyses [53,54] . The rest of studies which correlated tacrolimus with BK viremia and showed clearance of viremia upon reducing or withdrawing tacrolimus had small sample size (11 to 60 patients) and did not have control groups [95][96][97][98].…”

Section: Bk Association With Maintenance Immunosuppressant Therapymentioning

confidence: 99%

BK Virus Infection in Adult Renal Transplant Recipients; Risk Factors and their Impact on Allograft Survival

Alalawi¹,

Alnour²,

Kossi³

et al. 2020

Trends in Transplant

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Background: Since the discovery of BK Virus (BKV) in 1971, it became a growing challenge in the renal transplant field. Many hypotheses over the latest years have been made to justify the increased risk of acquiring BKV infection post-renal transplantation. Excessive immunosuppression remains the primary risk factor. Risk factors such as older recipients, male gender, prolonged cold ischemia time, ureteric stent insertion, degree of HLA mismatching and others have all been linked as additional risks for acquiring BKV infection. Nevertheless, the current literature on risk factors are inconclusive and no single identifiable risk factor can determine recipients who at risk. Objective:The objective of this review is to delineate and contemplate the potential risk factors published in the literature and leads to BKV nephropathy.Methodology: For this review, a variety of sources were utilised including EMBASE, Scopus, PubMed/Medline database and Google Scholar for observational studies on probable risk factors predisposing to BK viremia and/or nephropathy.Results: almost 22 distinctive risk factors were identified.Discussion: Over immunosuppression remains the major risk factor for acquiring BKV infection post-renal transplant, though it is uncertain whether the occurrence of BKVN (BKV Nephropathy) is owing to quantitative and/or qualitative differences in immune suppressants.Besides immunosuppression, other probable risk factors for BKV infection were recognized. Whilst some of them were reproducible in many of these studies, they were denied by others. For instance, ureteric stents, recipient's age, race, deceased-donor type and acute rejection episodes, were inconsistently recognised as significant risk factors for BKV infection. Conclusions:Over immunosuppression remained the reproducible risk factor for BKV infection in all studies, never the less published data on other risks factors varies. This may mirror the patient's geographical area, genetic vulnerability and probably a different BK gene variant with different risk susceptibility, these warrant further investigation.

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“…13 The use of mycophenolate has also been identified as a risk factor for BKPyV-DNAemia. 14,15 Nevertheless, another study that involved post-transplantation monitoring for BKPyV viruria for up to 2 years confirmed that the male sex was the only risk factor associated with sustained BKPyV-DNAemia or nephropathy. 16 Recent studies have stated that screening for BKPyV-DNAemia to identify asymptomatic patients at risk for kidney disease and reduced survival can prevent virus replication and stabilize allograft function,…”

Section: Introductionmentioning

confidence: 99%

“…Other risk factors have recently been reported, including human cytomegalovirus infection, an independent risk factor for JCPyV infection, receiving transplants with mismatched human leukocyte antigen (HLA), and making recipients more susceptible to BKPyV infection 13 . The use of mycophenolate has also been identified as a risk factor for BKPyV‐DNAemia 14,15 . Nevertheless, another study that involved post‐transplantation monitoring for BKPyV viruria for up to 2 years confirmed that the male sex was the only risk factor associated with sustained BKPyV‐DNAemia or nephropathy 16 .…”

Section: Introductionmentioning

confidence: 99%

A case‐control study to assess the role of polyomavirus in transplant complications: Where do we stand?

Urbán

Gurrado

Rivas

et al. 2020

Transplant Infectious Dis

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Purpose: The study's aim was to assess whether polyomavirus DNAemia screening was associated with different outcomes in patients with positive viremia compared with negative viremia. Methods: Case-control retrospective study of patients with polyomavirus DNAemia (viremia > 1000 copies/mL) matched 1:1 with controls. Control group consists of the patient who received a transplant immediately before or after each identified case and did have nil viremia. Finding: Ultimately, 120 cases of BK polyomavirus (BKPyV) were detected and matched with 130 controls. Of these, 54 were adult kidney transplant recipients (KTRs), 43 were pediatric KTRs, and 23 were undergoing hemato-oncologic therapy, of which 20 were undergoing hematopoietic stem cell transplantation. The odds ratio (OR) for overall risk of poorer outcomes in cases versus controls was 16.07 (95% CI: 5.55-46.54). The unfavorable outcome of switching the immunosuppressive drug (ISD) (14/40,35%) was no different from that of those treated with reduced ISD doses (31/71, 43.6%, P = .250). Acute rejection or graft-versus-host disease, previous transplant, and intensity of immunosuppression (4 ISDs plus induction or conditioning)

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Evaluation of the predisposition and clinical impact of BK virus replication in kidney transplant patients

Cited by 11 publications

References 29 publications

Posoleucel in Kidney Transplant Recipients with BK Viremia

Posoleucel in Kidney Transplant Recipients with BK Viremia

BK Virus Infection in Adult Renal Transplant Recipients; Risk Factors and their Impact on Allograft Survival

A case‐control study to assess the role of polyomavirus in transplant complications: Where do we stand?

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