Related Experiment Videos
Epstein-Barr virus-related disorders in children undergoing renal transplantation with tacrolimus-based
1Division of Nephrology, Children's Hospital of Pittsburgh, Pennsylvania 15213, USA.
Insights
Children receiving kidney transplants who are Epstein-Barr virus (EBV) negative and receive EBV-positive donor organs face a high risk of EBV complications. However, most patients achieve good outcomes with appropriate management.
Area of Science:
- Pediatric Nephrology
- Immunology
- Virology
Background:
- Epstein-Barr virus (EBV) related disorders are a significant complication in children undergoing renal transplantation, particularly under tacrolimus-based immunosuppression.
- Posttransplant lymphoproliferative disorder (PTLD) is a major concern in this patient population.
Purpose of the Study:
- To review EBV complications in children post-renal transplantation.
- To identify risk factors for EBV-related disorders, including PTLD.
- To evaluate the outcomes of EBV complications in pediatric renal transplant recipients.
Main Methods:
- Retrospective review of 81 children undergoing renal transplantation with pre-transplant EBV serological studies.
- Prospective monitoring of a subgroup of 30 children for EBV symptoms, signs, and immunological markers.
- Determination of donor EBV serology in the prospective subgroup.
- EBV-specific polymerase chain reaction (EBV-PCR) for viral load assessment.
Main Results:
- 19 out of 81 children developed symptomatic EBV infection, including infectious mononucleosis (7) and PTLD (10).
- Recipient seronegativity (EBV-) combined with donor seropositivity (EBV+) significantly predicted seroconversion and development of PTLD or malignancy (P<0.01).
- In the prospective subgroup, 15 of 19 EBV-seronegative recipients of EBV-positive grafts seroconverted, with 7 developing symptomatic EBV infection (3 with PTLD).
- All 19 children with EBV disorders resolved symptoms and maintained good allograft function.
Conclusions:
- EBV-seronegative pediatric renal transplant recipients of EBV-positive grafts are at high risk for EBV-related disorders under tacrolimus.
- Despite the risks, clinical outcomes for these EBV complications are generally good.
- These findings support the development of strategies for early risk identification and preventive/treatment measures.
Abstract:
In children undergoing renal transplantation, Epstein-Barr virus- (EBV) related disorders, including posttransplant lymphoproliferative disorder, constitute a major complication associated with tacrolimus-based immunosuppression. In this study, we reviewed the EBV complications in 81 children, all of whom had EBV serological studies before renal transplantation. We also highlight the data in a subgroup of 30 children transplanted more recently who were monitored sequentially for EBV symptoms and signs and with immunological studies, and in whom the donor EBV serology was also determined. During a mean follow-up time of 3.9+/-2.3 years, 19 children developed symptomatic Epstein-Barr virus (EBV*) infection. This consisted of the clinical syndrome of infectious mononucleosis in 7 children; in addition, 10 children developed posttransplant lymphoproliferative disorder (PTLD), which was histologically confirmed in 8, and 2 others developed malignant lymphoma. Recipient seronegativity (EBV-) and donor EBV seropositivity (EBV+) predicted a high probability for seroconversion (P=0.0072) and for developing PTLD or malignancy (P<0.01). In the subgroup of 30 children studied prospectively, seroconversion occurred in 15 of 19 seronegative recipients of EBV seropositive grafts at 6.6+/-2.6 months (mean+/-SD) after transplantation. Seven children developed symptomatic EBV infection (including three with PTLD) in association with seroconversion and a rise in EBV viral load in the peripheral blood, demonstrated by an EBV-specific polymerase chain reaction (EBV-PCR). Of 15 seroconverters, 7 who developed symptomatic infection had received EBV+ grafts; 8 others with EBV+ grafts seroconverted but did not become symptomatic. These two subgroups did not differ in age, rejection rate, antiviral prophylaxis, or level of immunosuppression. In the overall group of 81 children, only the two with malignant lymphoma who were managed with chemotherapy had substantial morbidity. The 10 individuals with PTLD received a regimen combining i.v. ganciclovir and CytoGam, and stopping or reducing the tacrolimus. Four children with associated marked tonsilar growth underwent tonsillectomy. All 19 individuals with EBV disorders resolved their symptoms and signs, and all have maintained good allograft function during a follow-up time of 3.0+/-2.5 years (mean+/-SD) after the development of symptomatic EBV infection, PTLD, or malignancy. We conclude that seronegative recipients of EBV+ grafts are at high risk for developing EBV-related disorders after renal transplantation under tacrolimus-based immunosuppression, although the ultimate clinical outcomes have been remarkably good. These data form the basis for formulating strategies for early identification of children at risk for EBV complications, and for instituting preventive and treatment strategies that permit these children to realize the substantial benefits offered by tacrolimus-based immunosuppression.