Serostatus-Driven Epstein–Barr Virus Management After Kidney Transplantation: Screening, Surveillance, and Pre-emptive Prevention of PTLD

By Elena GJECKA, Ariana STRAKOSHA, Silvia BINO

Abstract
Epstein–Barr virus (EBV) is a principal driver of post-transplant lymphoproliferative disorder (PTLD), one of the most serious complications of kidney transplantation. Because the risk of EBV-related disease is determined primarily by donor–recipient EBV serostatus, post-transplant EBV management is increasingly conceptualised as serostatus-driven. This narrative review synthesises evidence published predominantly within the last five years on EBV screening, post-transplant surveillance, interpretation of EBV DNA-emia, and pre-emptive prevention of PTLD in kidney transplant recipients, complemented by selected solid organ, paediatric, haematology, and laboratory-methodology studies. We argue that pre-transplant donor–recipient serology should define the baseline risk tier—high-risk donor-positive/recipient-negative (D+/R−), intermediate D−/R−, and lower-risk seropositive recipients—and thereby govern the intensity of monitoring, whereas viral-load kinetics, specimen type, assay calibration, immunosuppression exposure, and clinical context should govern intervention. Practical messages include the superiority of trend-based over single-threshold interpretation of EBV DNA-emia, the need for assay and specimen consistency in longitudinal follow-up, the limited role of antiviral prophylaxis, and the selective, evidence-informed use of immunosuppression reduction and preemptive rituximab in high-risk recipients. A six-step serostatus-driven algorithm is proposed to standardise screening, risk-adapted surveillance, interpretation of DNA-emia, pre-emptive intervention, and escalation to PTLD evaluation, while avoiding unnecessary testing or excessive immunosuppression reduction in lower-risk patients. Priorities for future research include international standardisation of EBV PCR, integration of EBV-specific immune monitoring into risk prediction, and prospective trials defining which recipients benefit from pre-emptive immune-directed therapy.
Keywords: Epstein–Barr virus; kidney transplantation; post-transplant lymphoproliferative disorder; serostatus; EBV DNA-emia; viral load monitoring; rituximab; pre-emptive therapy.