Epstein-Barr virus infection monitoring in kidney transplant recipients (EVITA study)-investigating the clinical significance of EBV-DNAemia and the risk of early-onset PTLD

Lene Ugilt Pagter Ludvigsen; Marianne Kragh Thomsen; Grete Birkeland Kro; Rune Micha Pedersen; Ann-Maria Gramkow; Anders Åsberg; Anna Kristina Bjerre; Helle Charlotte Thiesson; Karsten Midtvedt; Per Ivarsen; Søren Jensen-Fangel; Bo Martin Bibby; Stephen Hamilton-Dutoit; Francesco D'Amore; Anna Varberg Reisæter; Bente Jespersen

doi:10.1016/j.ajt.2026.07.012

Epstein-Barr virus infection monitoring in kidney transplant recipients (EVITA study)-investigating the clinical significance of EBV-DNAemia and the risk of early-onset PTLD

Am J Transplant. 2026 Jul 18:S1600-6135(26)02672-9. doi: 10.1016/j.ajt.2026.07.012. Online ahead of print.

Authors

Lene Ugilt Pagter Ludvigsen¹, Marianne Kragh Thomsen², Grete Birkeland Kro³, Rune Micha Pedersen⁴, Ann-Maria Gramkow⁵, Anders Åsberg⁶, Anna Kristina Bjerre⁷, Helle Charlotte Thiesson⁵, Karsten Midtvedt⁸, Per Ivarsen⁹, Søren Jensen-Fangel¹⁰, Bo Martin Bibby¹¹, Stephen Hamilton-Dutoit¹², Francesco D'Amore¹³, Anna Varberg Reisæter¹⁴, Bente Jespersen⁹

Affiliations

¹ Department of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark; Department of Infectious Diseases, Odense University Hospital, Odense, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. Electronic address: Lene.ugilt@auh.rm.dk.
² Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; Department of Clinical Microbiology, Aarhus University Hospital, Aarhus, Denmark.
³ Department of Clinical Microbiology, Oslo University Hospital, Oslo, Norway.
⁴ Department of Clinical Microbiology, Odense University Hospital, Odense, Denmark; Research Unit for Clinical Microbiology, University of Southern Denmark, Odense, Denmark.
⁵ Department of Nephrology, Odense University Hospital, Odense, Denmark; Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
⁶ Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway; The Norwegian Renal Registry, Oslo University Hospital, Oslo, Norway; Department of Pharmacy, University of Oslo, Oslo, Norway.
⁷ Division of Pediatrics and Adolescent Medicine, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
⁸ Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway.
⁹ Department of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
¹⁰ Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.
¹¹ Department of Biostatistics, Aarhus University, Aarhus, Denmark.
¹² Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; Department of Pathology, Aarhus University Hospital, Aarhus, Denmark.
¹³ Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; Department of Hematology, Aarhus University Hospital, Aarhus, Denmark.
¹⁴ Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway; The Norwegian Renal Registry, Oslo University Hospital, Oslo, Norway.

PMID: 42468757
DOI: 10.1016/j.ajt.2026.07.012

Abstract

Epstein-Barr virus (EBV) transmission from donor to naïve recipients (D+/R-) is a major risk for post-transplant lymphoproliferative disorder (PTLD). Blood EBV-DNA monitoring (EBV-DNAemia) is recommended, but the optimal blood matrix remains unclear. This 2-year prospective study of de novo kidney transplant recipients investigated the incidence and clinical significance of EBV-DNAemia in plasma and whole blood. The study estimated the positive and negative predictive values (PPV, NPV) of EBV-DNAemia kinetics for EBV-associated PTLD. Persistent EBV-DNAemia was examined as a predictor of excessive immunosuppression, defined by a composite endpoint of ≥2 infections requiring hospitalization, infection-related death, or EBV-associated PTLD. Of 509 enrolled recipients, 11 developed PTLD; 8 were EBV associated (20% of EBV D+/R- recipients, incidence rate = 8.0 (95% CI, 4.0-16.1) per 1000 patient-years). Plasma or whole-blood EBV-DNAemia were detected in 107 (21.0%) and 311 (61.1%) recipients, respectively, yielding an NPV >99% for EBV-associated PTLD in both matrices. PPVs were highest for a ≥3-fold increase in plasma EBV-DNA (PPV = 88.9%) and whole-blood EBV-DNA levels ≥50 000 IU/mL (PPV = 50.0%) among EBV D+/R- recipients. Persistent plasma EBV-DNAemia was associated with the composite endpoint (HR = 3.2; 95% CI, 1.8-5.7), predominantly driven by PTLD. Recognition of specific EBV-DNA kinetics in plasma and whole blood should promote clinical evaluation for PTLD.

Keywords: EBV; EBV infection; EBV-DNA; Epstein-Barr virus; PTLD; kidney transplantation; post-transplant complications; post-transplant lymphoproliferative disease.