Primary Epstein-Barr virus infection, seroconversion, and post-transplant lymphoproliferative disorder in seronegative renal allograft recipients: a prospective cohort study

Transpl Infect Dis. 2016 Jun;18(3):423-30. doi: 10.1111/tid.12533. Epub 2016 May 23.

Abstract

Background: Epstein-Barr virus (EBV)-seronegative renal transplant recipients are at risk of post-transplant lymphoproliferative disorder (PTLD). We compared primary EBV infection, seroconversion, and PTLD in EBV-seronegative patients who received renal allograft from seropositive or seronegative donors (D+/R- and D-/R-, respectively).

Methods: We prospectively followed 25 D+/R- and 8 D-/R- recipients. We followed patients from January 1999 to June 2009 with clinical visits, monthly EBV polymerase chain reaction tests, and serologic tests for a period of 1 year after kidney transplantation and on an individual basis thereafter.

Results: Three patients (9%) developed PTLD including 2 early-onset (<12 months) and 1 late-onset (>12 months) disease. In D+/R- and D-/R- patients, the frequencies of PTLD (8% vs. 12.5%, P = 0.7), EBV seroconversion (64% vs. 50%, P = 0.4), and EBV viremia (40% vs. 25%, P = 0.6) were not significantly different. Clinical, serologic, and virologic surveillance as well as reduction in immunosuppression after evidence of primary EBV infection resulted in a PTLD rate of 9%, despite a seroconversion rate of 60.6%. Rate of graft loss after reduction in immunosuppression was 10% (2 of 20), which was not significantly different from 13 patients without EBV seroconversion (no graft loss, P = 0.5). Rates of viremia, seroconversion, and PTLD in D+/R- and D-/R- patients appear to be similar.

Conclusions: The incidence of PTLD in renal transplants ranges from 0.5% to 2.9%. Our data show a significantly higher rate in EBV-seronegative renal allograft recipients, suggesting the need for close surveillance. Our data also suggest that donors for EBV-seronegative recipients may be accepted irrespective of positive or negative serostatus, with ongoing surveillance important in either circumstance.

Keywords: Epstein-Barr virus infection; immunosuppression; kidney transplantation; post-transplant lymphoproliferative disorder.

MeSH terms

  • Adult
  • Aged
  • Cohort Studies
  • Epstein-Barr Virus Infections / immunology*
  • Epstein-Barr Virus Infections / virology
  • Female
  • Herpesvirus 4, Human / immunology*
  • Humans
  • Immunosuppression Therapy
  • Kidney / immunology
  • Kidney / surgery
  • Kidney / virology
  • Kidney Transplantation / adverse effects*
  • Lymphoproliferative Disorders / etiology*
  • Lymphoproliferative Disorders / immunology
  • Male
  • Middle Aged
  • Postoperative Complications / immunology*
  • Postoperative Complications / virology
  • Prospective Studies
  • Seroconversion
  • Transplantation, Homologous / adverse effects
  • Viremia