Subclinical Epstein–Barr Virus Viremia Among Adult Renal Transplant Recipients: Incidence and Consequences

Bamoulid, Jamal; Courivaud, Cécile; Coaquette, A.; Chalopin, Jean-Marc; Gaiffe, Émilie; Saas, Philippe; Ducloux, Didier

doi:10.1111/ajt.12009

Cited by 68 publications

(99 citation statements)

References 16 publications

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“…In these patients, preemptive reduction of immunosuppression and treatments such as rituximab may reduce the incidence of early EBV-related disease and posttransplant lymphoproliferative disease (PTLD) (5)(6)(7). In adult kidney transplant recipients, PTLD is a late event, with median time to presentation in our population of 74 months (8,9).…”

Section: Introductionmentioning

confidence: 99%

Epstein–Barr Virus Infection in Adult Renal Transplant Recipients

Morton¹,

Coupes²,

Roberts

et al. 2014

American Journal of Transplantation

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Epstein-Barr virus (EBV) DNAemia in the first year posttransplantation has been studied extensively. There is a paucity of information on prevalence and sequelae of EBV infection in adult renal transplantation beyond the first year. This single-center study examines the relationship between EBV DNAemia and demographic, immunosuppressive, hematologic and infection-related parameters in 499 renal transplant recipients between 1 month and 33 years posttransplant. Participants were tested repeatedly for EBV DNAemia detection over 12 months and clinical progress followed for 3 years. Prevalence of DNAemia at recruitment increased significantly with time from transplant. In multivariate adjusted analyses, variables associated with DNAemia included EBV seronegative status at transplant (p ¼ 0.045), nonWhite ethnicity (p ¼ 0.014) and previous posttransplant lymphoproliferative disease (PTLD) diagnosis (p ¼ 0.006), while low DNAemia rates were associated with mycophenolate mofetil use (p < 0.0001) and EBV viral capsid antigen positive Epstein-Barr nuclear antigen-1 positive serostatus at transplant (p ¼ 0.044). Patient and graft survival, rate of kidney function decline and patient reported symptoms were not significantly different between EBV DNAemia positive and negative groups. EBV DNAemia is common posttransplant and increases with time from transplantation, but EBV DNAemia detection in low-risk (seropositive) patients has poor specificity as a biomarker for future PTLD risk.

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Section: Introductionmentioning

confidence: 99%

Epstein–Barr Virus Infection in Adult Renal Transplant Recipients

Morton¹,

Coupes²,

Roberts

et al. 2014

American Journal of Transplantation

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“…Cumulative incidence curves were constructed for study outcomes (overall and bacterial infection and CMV diseases) with death treated as a competing risk, and differences between groups were compared with the log-rank test. Uni-and multivariate Cox regression models were used to evaluate the association between iATP categories at each point (baseline and months 1 and 6 after transplantation) and outcomes throughout the following periods (early [first month], intermediate [months [1][2][3][4][5][6], and late periods [months [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24], respectively) [1]. Associations were expressed as hazard ratios (HRs) and 95% confidence intervals (CIs).…”

Section: Resultsmentioning

confidence: 99%

“…A detailed description of the 13 cases of CMV disease diagnosed in the intermediate period in which iATP levels at month 1 were available is provided as Supporting Information (Table S2). Finally, there were no significant differences in the incidence of infection at the end of the late period (i.e., months [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] according to the CMI response at month 6.…”

Section: Risk Of Infection Across Different Categories Of CMI Responsementioning

confidence: 99%

“…The application of immune monitoring strategies has been proposed as an approach to minimize the risk of such complication by tailoring immunosuppressive therapy to individual needs [2]. Different biomarkers [3][4][5][6][7] have been used as surrogates for the overall amount of immunosuppression, although most of these strategies are limited by the lack of technical standardization and validated cutoff values [2]. In addition, certain parameters -such as the enumeration of peripheral blood lymphocyte subpopulations (PBLSs) -do not provide functional insight into the recipient's immune response [2].…”

Section: Introductionmentioning

confidence: 99%

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Monitoring of intracellular adenosine triphosphate in CD4⁺T cells to predict the occurrence of cytomegalovirus disease in kidney transplant recipients

et al. 2016

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SUMMARYThe measurement of intracellular concentrations of adenosine triphosphate (iATP) in phytohemagglutinin-stimulated CD4 + T cells constitutes a surrogate marker for post-transplant cell-mediated immunity (CMI). This assay has shown suboptimal accuracy for predicting infection after kidney transplantation (KT). We hypothesize that its predictive capacity depends on the specific contribution of the CMI to host-pathogen interactions. We assessed iATP levels in 100 KT recipients at baseline and months 1, 3, and 6 (363 measurements). No association was found between iATP at month 1 and the risk for overall or bacterial infection, although such association was evident for cytomegalovirus (CMV) disease (multivariate-adjusted hazard ratio [per 50-unit increment]: 0.83; Pvalue = 0.048). There were no significant differences in mean iATP between stable patients (319.4 ng/ml) and those developing overall (304.1 ng/ml) or bacterial infection (346.9 ng/ml) over the 45 days following monitoring. However, iATP was significantly lower in patients who developed CMV disease (223.5 ng/ml; P-values <0.002). The optimal cutoff (265 ng/ml) for predicting CMV disease in patients not receiving antiviral prophylaxis yielded sensitivity, specificity, positive, and negative predictive values of 85.7%, 68.3%, 15.2%, and 98.6%, respectively. In conclusion, a non-pathogen-specific monitoring of CMI by means of iATP informs the risk of CMV disease in KT recipients.

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“…Induction therapies such as T cell-depleting polyclonal antibodies are often associated with an increased incidence of infection (12), Epstein-Barr virus (EBV) reactivation and posttransplant lymphoproliferative disorder (PTLD) (13). Data from large cohorts of transplant patients from European and US registries suggested that the incidence of PTLD is not increased with the use of anti-T-lymphocyte globulins ATG-Fresenius (ATG-F) or anti-CD25 mAb (14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

Early Corticosteroid Avoidance in Kidney Transplant Recipients Receiving ATG-F Induction: 5-Year Actual Results of a Prospective and Randomized Study

Cantarovich

Rostaing

Kamar

et al. 2014

American Journal of Transplantation

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One hundred ninety-seven patients received anti-Tlymphocyte globulins Fresenius, mycophenolate mofetil and delayed cyclosporine, and were randomized to !6-month corticosteroids (þCS; n ¼ 99) or no CS (ÀCS; n ¼ 98). One-and five-year actual graft survival (censored for death) was 93.2% and 86.4% in the þCS group versus 94.9% and 89.8% in the ÀCS group (5-year follow-up, p ¼ 0.487). Freedom from clinical rejection was 86.9% and 81.8% versus 74.5% and 74.5% (p ¼ 0.144), respectively, at 1 and 5 years; 5-year freedom from biopsyproven rejection was 88.9% versus 83.7% (p ¼ 0.227). More late first rejections occurred in the þCS group. Significantly lower 5-year graft survival in patients experiencing rejection was observed for þCS (55.6% vs. 92.0%; p ¼ 0.005) with 8/18 versus 2/25 graft losses. Renal function at 5 years was stable and comparable (median serum creatinine, 159 vs. 145 mmol/L; creatinine clearance, 53.5 vs. 56.6 mL/min). More þCS patients developed diabetes, dyslipidemia and malignancies. Rejections in ÀCS patients occurred early after transplantation and did not impair long-term renal function. In patients receiving CS, rejections occurred later and with a higher risk for subsequent graft failure. A similar and not inferior 5-year efficacy profile and a reduced morbidity were observed in CS-free patients compared to patients who received CS for at least 6 months.

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Subclinical Epstein–Barr Virus Viremia Among Adult Renal Transplant Recipients: Incidence and Consequences

Cited by 68 publications

References 16 publications

Epstein–Barr Virus Infection in Adult Renal Transplant Recipients

Epstein–Barr Virus Infection in Adult Renal Transplant Recipients

Monitoring of intracellular adenosine triphosphate in CD4⁺T cells to predict the occurrence of cytomegalovirus disease in kidney transplant recipients

Early Corticosteroid Avoidance in Kidney Transplant Recipients Receiving ATG-F Induction: 5-Year Actual Results of a Prospective and Randomized Study

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Subclinical Epstein–Barr Virus Viremia Among Adult Renal Transplant Recipients: Incidence and Consequences

Cited by 68 publications

References 16 publications

Epstein–Barr Virus Infection in Adult Renal Transplant Recipients

Epstein–Barr Virus Infection in Adult Renal Transplant Recipients

Monitoring of intracellular adenosine triphosphate in CD4+T cells to predict the occurrence of cytomegalovirus disease in kidney transplant recipients

Early Corticosteroid Avoidance in Kidney Transplant Recipients Receiving ATG-F Induction: 5-Year Actual Results of a Prospective and Randomized Study

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Monitoring of intracellular adenosine triphosphate in CD4⁺T cells to predict the occurrence of cytomegalovirus disease in kidney transplant recipients