Ludvigsen Lene Ugilt Pagter, Åsberg Anders, Spetalen Signe, Sørensen Mia Dahl, Hamilton-Dutoit Stephen, Gramkow Ann-Maria, Christiansen Christian Fynbo, Kro Grete Birkeland, Thomsen Marianne Kragh, Ulrichsen Sinna Pilgaard, Pedersen Rune Micha, Holte Harald, Thiesson Helle Charlotte, Bjerre Anna, D'Amore Francesco, Dahle Dag Olav, Jespersen Bente, Jensen-Fangel Søren, Reisæter Anna Varberg
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.
Department of Transplantation Medicine, Oslo University Hospital, Rikshospitalet, Norway; The Norwegian Renal Registry, Oslo University Hospital, Rikshospitalet, Norway; Department of Pharmacy, University of Oslo, Oslo, Norway.
Am J Transplant. 2025 Jul;25(7):1547-1560. doi: 10.1016/j.ajt.2025.01.035. Epub 2025 Jan 28.
Posttransplant lymphoproliferative disorder (PTLD) poses a serious challenge in kidney transplant recipients. Epstein-Barr virus (EBV)-seronegative recipients have a significantly increased risk of PTLD, but few studies have investigated risk factors for PTLD in EBV-seronegative recipients in the current era of immunosuppression. This cohort study from Norway and western Denmark included first-time kidney transplant recipients between 2007 and 2021 and estimated the cumulative incidence, risk, and prognosis of PTLD. In total, 80 of 5084 recipients developed biopsy-proven PTLD (median follow-up of 6.8 years). Two-year cumulative incidence of PTLD was 7.3% in EBV-seronegative adults and 14.1% in EBV-seronegative children. The age-adjusted hazard ratio (HR) for PTLD was 30.7 (95% CI, 13.9-67.9) in EBV-seronegative vs EBV-seropositive adults and 5.4 (95% CI, 1.1-26.9) in children. Recipients receiving induction therapy with antithymocyte globulin had an increased risk of PTLD (HR, 4.4; 95% CI, 1.8-10.6), while rituximab induction was associated with a lower risk of PTLD (HR, 0.20; 95% CI, 0.03-1.49). The age-adjusted mortality rate was higher in EBV-seronegative recipients with vs without PTLD (HR, 3.3; 95% CI, 1.3-8.3). In conclusion, the risk of PTLD in EBV-seronegative kidney transplant recipients is high in the contemporary era of immunosuppression. Induction therapy should be carefully considered in this high-risk population.
移植后淋巴细胞增生性疾病（PTLD）给肾移植受者带来了严峻挑战。爱泼斯坦-巴尔病毒（EBV）血清学阴性的受者发生PTLD的风险显著增加，但在当前免疫抑制时代，很少有研究调查EBV血清学阴性受者发生PTLD的危险因素。这项来自挪威和丹麦西部的队列研究纳入了2007年至2021年期间的首次肾移植受者，并估计了PTLD的累积发病率、风险和预后。在5084名受者中，共有80人经活检证实发生了PTLD（中位随访时间为6.8年）。EBV血清学阴性的成年人PTLD的两年累积发病率为7.3%，儿童为14.1%。EBV血清学阴性的成年人与EBV血清学阳性的成年人相比，PTLD的年龄调整后风险比（HR）为30.7（95%CI，13.9-67.9），儿童为5.4（95%CI，1.1-26.9）。接受抗胸腺细胞球蛋白诱导治疗的受者发生PTLD的风险增加（HR，4.4；95%CI，1.8-10.6），而利妥昔单抗诱导治疗与较低的PTLD风险相关（HR，0.20；95%CI，0.03-1.49）。有PTLD的EBV血清学阴性受者与无PTLD的相比，年龄调整后的死亡率更高（HR，3.3；95%CI，1.3-8.3）。总之，在当代免疫抑制时代，EBV血清学阴性的肾移植受者发生PTLD的风险很高。对于这一高风险人群，应谨慎考虑诱导治疗。
