Pediatric renal transplantation: A retrospective single‐center study on epidemiology and morbidity due to EBV

Laurent, Audrey; Klich, Amna; Roy, Pascal; Lina, Bruno; Kassai, Behrouz; Bacchetta, Justine; Cochat, Pierre

doi:10.1111/petr.13151

Cited by 13 publications

(11 citation statements)

References 41 publications

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“…The median CHL duration of 2 years is similar to the results of other studies, but the follow-up time of almost 8 years is longer than other comparable studies [18,27,33]. In a previous multicenter study, 2% of PTLD was reported following renal transplantation [34]. In our study of 58 children, there were no cases of PTLD, which also might be due to the limited study size.…”

Section: Discussionsupporting

confidence: 88%

“…The median time to onset of CHL in our cohort was 69 days post-transplant which is shorter than the 104 days in a previous study [32]. The median CHL duration of 2 years is similar to the results of other studies, but the follow-up time of almost 8 years is longer than other comparable studies [18,27,33]. In a previous multicenter study, 2% of PTLD was reported following renal transplantation [34].…”

Section: Discussionsupporting

confidence: 83%

“…Young age is a well-known risk factor for developing chronic high EBV load and PTLD [14,34]. In our study, CHL was more frequent in young individuals and the children in the CHL-group were younger (median age 2 years) than described by Yamada et al (median age 3.8 years) [27].…”

Section: Discussionsupporting

confidence: 47%

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Long-lasting chronic high load carriage of Epstein-Barr virus is more common in young pediatric renal transplant recipients

et al. 2019

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Background Epstein-Barr virus (EBV) infections can induce post-transplant lymphoproliferative disorder (PTLD). A chronic high load (CHL), as indicated by long-term high EBV DNA levels after transplantation, has been associated with an enhanced risk of PTLD. We aimed to evaluate incidence, time of occurrence, risk factors, and outcome of EBV CHL carrier state after pediatric renal transplantation. Methods A retrospective study of 58 children aged 1-17 years (median 10), who underwent renal transplantation between January 2004 and June 2017 at a single medical center. EBV IgG antibodies in serum were analyzed before and yearly after transplantation. EBV DNA in whole blood were analyzed weekly for the first 3 months post-transplant, monthly up to 1 year and then at least once yearly. CHL was defined as EBV DNA ≥ 4.2 log 10 Geq/ml in > 50% of the samples during ≥ 6 months. Results At transplantation, 31 (53%) patients lacked EBV IgG and 25 (81%) of them developed primary EBV infection posttransplant. Of the 27 seropositive patients, 20 (74%) experienced reactivation of EBV. Altogether, 14 (24%) children developed CHL, starting at a median of 69 days post-transplant and lasting for a median time of 2.3 years (range 0.5-6.5), despite reduction of immunosuppression. Patients with CHL were younger and 11/14 were EBV seronegative at transplantation. No child developed PTLD during median clinical follow-up of 7.8 years (range 0.7-13). Conclusions CHL was frequent, long lasting, and occurred mainly in young transplant recipients. The absence of PTLD suggests that monitoring of EBV DNA to guide immunosuppression was effective.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 83%

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Long-lasting chronic high load carriage of Epstein-Barr virus is more common in young pediatric renal transplant recipients

et al. 2019

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“…The immunosuppressive treatment impairs the individual cellular immune response resulting in an elevated incidence of severe viral complications, notably after pediatric transplantation. Post-transplant primary infections or reactivations, especially by cytomegalovirus (CMV), BK polyomavirus (BKPyV), or Epstein-Barr virus (EBV) are associated with increased morbidity, mortality, and graft failure, for example from CMV disease [ 7 , 8 ], BKPyV-associated nephropathy [ 9 , 10 ], and EBV-associated post-transplant lymphoproliferative disease [ 11 ]. The outcome of post-transplant viral infections is individually different, but prognostic markers are missing.…”

Section: Introductionmentioning

confidence: 99%

Novel ways to monitor immunosuppression in pediatric kidney transplant recipients—underlying concepts and emerging data

Ahlenstiel-Grunow

Pape

2021

Mol Cell Pediatr

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After pediatric kidney transplantation, immunosuppressive therapy is given to avoid acute and chronic rejections. However, the immunosuppression causes an increased risk of severe viral complications and bacterial infections and is associated with serious side effects. It is therefore crucial to achieve the optimal individual balance between over- and under-immunosuppression and thereby avoid unnecessary exposure to immunosuppressive drugs. In routine use, steering of immunosuppressants is performed primarily by monitoring of trough levels that mirror pharmacokinetics (although not, however, pharmacodynamics). Other diagnostic and prognostic markers to assess the individual intensity of immunosuppression are missing. Potential methods to determine immune function and grade of immunosuppression, such as analysis of the torque teno virus (TTV) load, QuantiFERON Monitor®, and ImmuKnow® as well as virus-specific T cells (Tvis), are currently being evaluated. In some studies TTV load, QuantiFERON Monitor® and ImmuKnow® were associated with the risk for post-transplant rejections and infections, but randomized controlled trials after pediatric kidney transplantation are not available. Post-transplant monitoring of Tvis levels seem to be promising because Tvis control virus replication and have been shown to correlate with virus-specific as well as general cellular immune defense, which represents the individual’s susceptibility to infections. Additional Tvis-monitoring provides an innovative opportunity to personalize the antiviral management and the dosing of the immunosuppressive therapy after pediatric kidney transplantation to avoid unnecessary therapeutic interventions and identify over-immunosuppression.

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“…After pediatric kidney transplantation, the immunosuppressive treatment disturbs the individual balance between virus replication and cellular immune response resulting in an elevated incidence of severe viral complications. Post-transplant primary infections or reactivations, especially by cytomegalovirus (CMV), BK polyomavirus (BKPyV) or Epstein-Barr virus (EBV), and less frequent by adenovirus (ADV), are associated with increased morbidity, mortality, and graft failure, for example, CMV disease [1], BKPyV-associated nephropathy (BKPyVAN) [2], and EBV-associated post-transplant lymphoproliferative disease (PTLD) [3]. The outcome of post-transplant viral infections is individually different, but prognostic markers are missing.…”

Section: Introductionmentioning

confidence: 99%

Virus-specific T cells in pediatric renal transplantation

Ahlenstiel-Grunow

Pape

2020

Pediatr Nephrol

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After pediatric kidney transplantation, immunosuppressive therapy causes an increased risk of severe viral complications, especially from cytomegalovirus (CMV), BK polyomavirus (BKPyV) or Epstein-Barr virus (EBV), and less frequent from adenovirus (ADV). However, suitable predictive markers for the individual outcome of viral infections are missing and the therapeutic management remains a challenge to the success of pediatric kidney transplantation. Virus-specific T cells are known for controlling viral replication and there is growing evidence that virus-specific T cells may serve as a prognostic marker to identify patients at risk for viral complications. This review provides an overview of the usability of virus-specific T cells for improving diagnostic and therapeutic management of viral infections with reference to the necessity of antiviral prophylaxis, timing of pre-emptive therapy, and dosing of immunosuppressive medication after pediatric kidney transplantation. Several studies demonstrated that high levels of virus-specific T cells are associated with decrease of virus load and favorable outcome, whereas lack of virus-specific T cells coincided with virus-induced complications. Accordingly, the additional monitoring of virus-specific T cells aims to personalize the management of antiviral therapy, identify overimmunosuppression, and avoid unnecessary therapeutic interventions. Prospective randomized trials in pediatric kidney recipients comparing standard antiviral and immunosuppressive regimens with T cell-guided therapeutic interventions are needed, before monitoring of virus-specific T cells is implemented in the routine care of pediatric kidney graft recipients.

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Pediatric renal transplantation: A retrospective single‐center study on epidemiology and morbidity due to EBV

Cited by 13 publications

References 41 publications

Long-lasting chronic high load carriage of Epstein-Barr virus is more common in young pediatric renal transplant recipients

Long-lasting chronic high load carriage of Epstein-Barr virus is more common in young pediatric renal transplant recipients

Novel ways to monitor immunosuppression in pediatric kidney transplant recipients—underlying concepts and emerging data

Virus-specific T cells in pediatric renal transplantation

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