Data_Sheet_1_Pre-transplant Thymic Function Predicts Is Associated With Patient Death After Kidney Transplantation.doc

Accelerated thymic involution is a main feature of end-stage renal disease (ESRD)-associated immune senescence. Recent evidences suggest that ESRD-associated immune senescence is associated with adverse outcomes in dialysis patients. However, no study focused on the association between pre-transplant thymic function and patient survival after transplantation. We conducted a prospective, multicenter study to assess whether pre-transplant thymic function measured by recent thymic emigrants (RTE) may predict death after first kidney transplantation. Results were tested in a validation cohort. Nine hundred and sixty-seven incident kidney transplant recipients were included in the prospective study. Mean follow up was 5.1 + 2.9 years. Eighty two patients (8.5%) died during follow up. Lower RTE levels were associated with a higher risk of death (2.53; 95%CI, 1.54–4.39 for each decrease of 1 log in RTE; p < 0.001). Cancer-related death was particularly increased in patients with low RTE levels (4.23; 95%CI, 1.43–12.13; p = 0.007). One hundred and thirty-six patients having received a first kidney transplantation were included in the validation cohort. Lower TREC levels were associated with higher risk of death (1.90; 95%CI, 1.11–3.51 for each decrease of 1 log in RTE; p = 0.025). RTE were not associated with death-censored graft loss. Pre-transplant thymic function is strongly associated with death after transplantation. Attempt to reverse ESRD-related thymic loss may prevent premature death.

胸腺加速退化是终末期肾病（end-stage renal disease, ESRD）相关免疫衰老的主要特征。近期研究证据表明，终末期肾病相关免疫衰老与透析患者的不良预后存在关联。然而，目前尚无研究聚焦于移植术前胸腺功能与肾移植术后患者生存率之间的相关性。本研究开展了一项前瞻性多中心研究，旨在评估通过近期胸腺迁出细胞（recent thymic emigrants, RTE）检测的移植前胸腺功能，是否可预测首次肾移植术后的死亡风险。研究结果在验证队列中得到检验。本前瞻性研究共纳入967例新发肾移植受者，平均随访时长为5.1±2.9年，随访期间共有82例患者（占比8.5%）死亡。较低的近期胸腺迁出细胞水平与更高的死亡风险显著相关（近期胸腺迁出细胞每降低1个对数级，风险比为2.53；95%置信区间1.54~4.39；p<0.001）。其中，低近期胸腺迁出细胞水平患者的癌症相关死亡风险尤为升高（风险比4.23；95%置信区间1.43~12.13；p=0.007）。验证队列共纳入136例首次肾移植受者，较低的T细胞受体切除环（T cell receptor excision circles, TREC）水平与更高的死亡风险相关（近期胸腺迁出细胞每降低1个对数级，风险比为1.90；95%置信区间1.11~3.51；p=0.025）。近期胸腺迁出细胞水平与死亡删失移植物失功无显著关联。综上，移植前胸腺功能与肾移植术后死亡风险密切相关。干预逆转终末期肾病相关的胸腺损失，或可预防患者过早死亡。