Risk factors for Epstein–Barr virus reactivation after renal transplantation: Results of a large, multi‐centre study

Abstract

Summary Epstein–Barr virus (EBV) reactivation is a very common and potentially lethal complication of renal transplantation. However, its risk factors and effects on transplant outcome are not well known. Here, we have analysed a large, multi‐centre cohort (N = 512) in which 18.4% of the patients experienced EBV reactivation during the first post‐transplant year. The patients were characterized pre‐transplant and two weeks post‐transplant by a multi‐level biomarker panel. EBV reactivation was episodic for most patients, only 12 patients showed prolonged viraemia for over four months. Pre‐transplant EBV shedding and male sex were associated with significantly increased incidence of post‐transplant EBV reactivation. Importantly, we also identified a significant association of post‐transplant EBV with acute rejection and with decreased haemoglobin levels. No further severe complications associated with EBV, either episodic or chronic, could be detected. Our data suggest that despite relatively frequent EBV reactivation, it had no association with serious complications during the first post‐transplantation year. EBV shedding prior to transplantation could be employed as biomarkers for personalized immunosuppressive therapy. In summary, our results support the employed immunosuppressive regimes as relatively safe with regard to EBV. However, long‐term studies are paramount to support these conclusions.

Single-Center Outcomes of Epstein–Barr Virus DNAemia in Adult Solid Organ Transplant Recipients

“…We found the highest proportion of EBV DNAemia in subjects who were D+/R− at time of transplant (37.5%) compared with rates of 3.5% and 0% in the R+ and D−/R− groups, respectively. The overall rate of EBV DNAemia in this study is lower than in previous reports in adult SOT recipients (13–67%) [ 6 , 8 – 10 , 24 – 26 ]. Most recently, Blazquez-Navarro et al observed 18.4% of patients in a multicenter cohort experienced EBV reactivation in the first posttransplant year [ 6 ].…”

“…The overall rate of EBV DNAemia in this study is lower than in previous reports in adult SOT recipients (13–67%) [ 6 , 8 – 10 , 24 – 26 ]. Most recently, Blazquez-Navarro et al observed 18.4% of patients in a multicenter cohort experienced EBV reactivation in the first posttransplant year [ 6 ]. The infrequent screening in our cohort may have led to underestimation of rates of EBV DNAemia.…”

“…A substantial proportion of D+/R− subjects (3/8, 37.5%) did not have EBV screening performed. No differences were identified in rates of EBV DNAemia according to immunosuppression, including ATG induction [ 6 , 8 ].…”

“…EBV plays a predominant role in early PTLD within the first year of transplant and is found in the majority of early diagnoses [ 1 – 5 ]. Previously noted risk factors for both EBV DNAemia and PTLD have relied on single-center studies as well as larger registry datasets [ 2 – 4 , 6 , 7 ]. The most notable risk factor for both EBV DNAemia and PTLD has been donor/recipient mismatch of EBV serostatus (donor seropositive, recipient seronegative; D+/R−) [ 1 , 6 , 7 ].…”

“…Previously noted risk factors for both EBV DNAemia and PTLD have relied on single-center studies as well as larger registry datasets [ 2 – 4 , 6 , 7 ]. The most notable risk factor for both EBV DNAemia and PTLD has been donor/recipient mismatch of EBV serostatus (donor seropositive, recipient seronegative; D+/R−) [ 1 , 6 , 7 ]. Other risk factors for EBV DNAemia posttransplant include antithymocyte globulin (ATG) induction treatment as well as CMV mismatch [ 6 , 8 – 10 ].…”