ABSTRACT Background Prior studies and guidelines emphasize PTLD‐risk for Epstein–Barr virus (EBV) mismatched (D+/R−) recipients. However, risk among D−/R− kidney recipients remains poorly defined. We evaluated PTLD‐risk by donor–recipient EBV serostatus, including D−/R−, and time‐varying impact of PTLD on mortality in kidney transplant recipients. Methods This retrospective cohort included deceased donor kidney transplants from the US Scientific Registry of Transplant Recipients (2003–2023). Recipient and donor‐recipient EBV serostatus were categorical exposures. Time‐to‐PTLD was analyzed using Kaplan–Meier methods and adjusted Cox models, stratified into 0–1, 1–2, and 2–3 years to address non‐proportional hazards. Secondary outcomes included mortality and all‐cause graft failure (ACGF), with PTLD modeled as a time‐dependent exposure. Effect modification across key subgroups was evaluated. Results Among 309 585 recipients (2.35 million person‐years), 3147 PTLD events (1.1%) occurred, largely within the first year. Incidence was highest for D+/R− (3%) and D−/R− (1.8%) ( p < 0.001). First‐year PTLD‐risk was highest for D+/R− (HR 17.8 95% CI: 10.4, 30.5) and D−/R− (HR 8.2 95% CI: 4.2, 15.8) recipients. PTLD was associated with increased mortality (HR 4.5 95% CI: 4.3, 4.8) and ACGF (HR 3.7 95% CI: 3.5, 3.9), with relatively higher mortality‐risk for pediatric recipients (ratio of HRs 1.5). Among 82 detailed PTLD cases, most were B‐cell (89%), monoclonal (63%), and EBV‐positive (78%), with mixed WHO class and site‐involvement. Conclusions EBV D+/R− recipients experienced highest and sustained 3‐year PTLD‐risk, while D−/R− recipients faced previously under‐recognized early risk. PTLD was strongly linked to mortality and ACGF, refining counselling and supporting targeted surveillance for high‐risk groups. image
Rampersad et al. (Mon,) studied this question.
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