An observational cohort study of histological screening for BK polyomavirus nephropathy following viral replication in plasma

Cleenders, Evert; Koshy, Priyanka; Van Loon, Elisabet; Lagrou, Katrien; Beuselinck, Kurt; Andrei, Graciela; Crespo, Marta; De Vusser, Katrien; Kuypers, Dirk; Lerut, Evelyne; Mertens, Kris; Mineeva-Sangwo, Olga; Randhawa, Parmjeet; Senev, Aleksandar; Snoeck, Robert; Sprangers, Ben; Tinel, Claire; Van Craenenbroeck, Amaryllis; van den Brand, Jan; Van Ranst, Marc; Verbeke, Geert; Coemans, Maarten; Naesens, Maarten

doi:10.1016/j.kint.2023.07.025

Cited by 11 publications

(15 citation statements)

References 34 publications

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“…18 A recent study by Cleenders et al of 950 kidney transplant recipients identified later development of acute rejection as a risk factor for graft failure in those with BKV viremia. 36 Although we did not observe any association between BKV and graft loss, our study was limited by a small number of patients with BKV who had few graft loss events. Given the association between BKV and TCMR, it is likely that an association with graft failure may be seen with longer follow-up and/or larger cohort.…”

Section: Discussionmentioning

confidence: 53%

Association of BKV viremia and nephropathy with adverse alloimmune outcomes in kidney transplant recipients

Rampersad,

Wiebe,

Balshaw

et al. 2024

Clinical Transplantation

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BackgroundImmunosuppression reduction for BK polyoma virus (BKV) must be balanced against risk of adverse alloimmune outcomes. We sought to characterize risk of alloimmune events after BKV within context of HLA‐DR/DQ molecular mismatch (mMM) risk score.MethodsThis single‐center study evaluated 460 kidney transplant patients on tacrolimus‐mycophenolate‐prednisone from 2010‐2021. BKV status was classified at 6‐months post‐transplant as “BKV” or “no BKV” in landmark analysis. Primary outcome was T‐cell mediated rejection (TCMR). Secondary outcomes included all‐cause graft failure (ACGF), death‐censored graft failure (DCGF), de novo donor specific antibody (dnDSA), and antibody‐mediated rejection (ABMR). Predictors of outcomes were assessed in Cox proportional hazards models including BKV status and alloimmune risk defined by recipient age and molecular mismatch (RAMM) groups.ResultsAt 6‐months post‐transplant, 72 patients had BKV and 388 had no BKV. TCMR occurred in 86 recipients, including 27.8% with BKV and 17% with no BKV (p = .05). TCMR risk was increased in recipients with BKV (HR 1.90, (95% CI 1.14, 3.17); p = .01) and high vs. low‐risk RAMM group risk (HR 2.26 (95% CI 1.02, 4.98); p = .02) in multivariable analyses; but not HLA serological MM in sensitivity analysis. Recipients with BKV experienced increased dnDSA in univariable analysis, and there was no association with ABMR, DCGF, or ACGF.ConclusionsRecipients with BKV had increased risk of TCMR independent of induction immunosuppression and conventional alloimmune risk measures. Recipients with high‐risk RAMM experienced increased TCMR risk. Future studies on optimizing immunosuppression for BKV should explore nuanced risk stratification and may consider novel measures of alloimmune risk.

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Section: Discussionmentioning

confidence: 53%

Association of BKV viremia and nephropathy with adverse alloimmune outcomes in kidney transplant recipients

Rampersad,

Wiebe,

Balshaw

et al. 2024

Clinical Transplantation

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“…Consensus groups use BK viremia of $10,000 copies/ml as a noninvasive marker for presumptive BK virus-associated nephropathy. 6,19 However, clinicians often start decreasing immunosuppression before BK viremia reaches values of 10,000 copies/ml, with many nephrologists decreasing immunosuppression when BK viremia reaches levels around 5000 copies/ml. Thus, we also evaluated the treatment effect of posoleucel in participants with BK viremia $5000 copies/ml who were within 2 years after kidney transplantation with stable immunosuppression before randomization.…”

Section: Secondary Outcomesmentioning

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%

“…3,4 Clinically, high-level (.10,000 copies/ml) BK viremia is considered presumptive BK virus-associated nephropathy. 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.…”

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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“…A recent Belgian study with systematic biopsy and BKPyV-DNA load follow-up has shown a very high negative predictive value (0.989) when the plasma viral load was below 10 4 copies/mL. Performing a biopsy for confirmation of BKPyV nephropathy is therefore not necessary in cases of low viral load [38].…”

Section: Bkpyv Viremiamentioning

confidence: 99%

BK Polyomavirus in Pediatric Renal Transplantation—What We Know and What We Do Not

Chiodini,

Guillaume-Gentil,

Vanhomwegen

et al. 2024

Biomedicines

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BK polyomavirus (BKPyV) is still a real threat in the management of kidney transplantation. Immunosuppressive treatment disrupts the equilibrium between virus replication and immune response, and uncontrolled BKPyV replication leads to nephropathy (BKPyV nephropathy). The first evidence of BKPyV reactivation in transplant recipients is the detection of viral shedding in urine, which appears in 20% to 60% of patients, followed by BKPyV viremia in 10–20% of kidney transplant recipients. BKPyV nephropathy eventually occurs in 1–10% of this population, mainly within the first 2 years post-transplantation, causing graft loss in about half of those patients. Few data exist regarding the pediatric population and we focus on them. In this paper, we review the existing diagnostic methods and summarize the evidence on the role of BKPyV humoral and cellular immunity in modulating the clinical course of BKPyV infection and as potential predictors of the outcome. We look at the known risk factors for BKPyV nephropathy in the immunosuppressed patient. Finally, we propose a sensible clinical attitude in order to screen and manage BKPyV infection in kidney transplant children.

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An observational cohort study of histological screening for BK polyomavirus nephropathy following viral replication in plasma

Cited by 11 publications

References 34 publications

Association of BKV viremia and nephropathy with adverse alloimmune outcomes in kidney transplant recipients

Association of BKV viremia and nephropathy with adverse alloimmune outcomes in kidney transplant recipients

Posoleucel in Kidney Transplant Recipients with BK Viremia

BK Polyomavirus in Pediatric Renal Transplantation—What We Know and What We Do Not

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