Background

The association of mammalian target of rapamycin inhibitors (MTORI) with malignancies and mortality in kidney transplant recipients (KTR) with different degrees of human leukocyte antigen mismatch (HLA-mm) at transplant has not been previously studied.

Methods

Our observational cohort study included 166, 256 adult KTRs in 2000–2018. Immunosuppression in the first post-transplant year were MTORIs in 13,056 (7.85%) and non-MTORIs in 153,200 (92.15%). We used Cox multivariable regression models to determine the cause-specific hazard ratio (HRcs) of non-melanoma skin cancer (NMSC),solid organ malignancies (SOM)] and all-cause death (death_ac); and the HR of the composite outcomes of NMSC or death_ac and SOM or death_ac associated with MTORI versus non-MTORI regimens in the overall study sample and the 0, 1–3, and 4–6 HLA-A, B and DR mm subgroups.

Results

NMSC risk was lower with MTORI than non-MTORI in all HLA-mm subgroups [(0 mm, HRcs = 0.67; 95% CI = 0.46–0.97, 1–3 mm, HRcs = 0.73; 95% CI = 0.61–0.87, 4–6 mm, HRcs = 0.69; 95% CI = 0.62–0.76)]. SOM risks were similar between regimens in the 0 HLA mm subgroup (HRcs = 1.10 (95% CI = 0.78–1.57) and lower with MTORI than non-MTORI in the 1–3, and 4–6 HLA-mm subgroups, [(HR = 0.84; (95% CI = 0.71–0.99), and (HR = 0.86; 95% CI = 0.78–0.94); respectively]. Risks of death_ac and composite outcomes (NMSC or death_ac and SOM or death_ac) were higher with MTORI than non-MTORI in almost all HLA-mm subgroups.

Conclusion

MTORIs are associated with protection from NMSC and SOM in almost all HLA-mm subgroups ca; however, their association with increased all-cause mortality in adult kidney transplant recipients needs further investigation.

背景

哺乳动物雷帕霉素抑制剂靶点 (MTORI) 与移植时不同程度的人类白细胞抗原错配 (HLA-mm) 的肾移植受者 (KTR) 的恶性肿瘤和死亡率之间的关联尚未得到研究。

方法

我们的观察性队列研究包括 2000-2018 年的 166、256 名成人 KTR。移植后第一年的免疫抑制是 MTORIs 13,056 (7.85%) 和非 MTORIs 153,200 (92.15%)。我们使用 Cox 多变量回归模型来确定非黑色素瘤皮肤癌 (NMSC)、实体器官恶性肿瘤 (SOM)] 和全因死亡 (death _ac )的病因特异性风险比 (HRcs )；以及整个研究样本中 NMSC 或死亡_ac和 SOM 或死亡_ac与 MTORI 与非 MTORI 方案相关的复合结果的 HR 以及 0、1-3和 4-6 HLA-A、B 和 DR mm亚组。

结果

在所有 HLA-mm 亚组中，MTORI 的 NMSC 风险低于非 MTORI [（0 mm，HRcs = 0.67；95% CI = 0.46–0.97，1–3 mm，HRcs = 0.73；95% CI = 0.61–0.87， 4–6 毫米，HRcs = 0.69；95% CI = 0.62–0.76)]。在 0 HLA mm 亚组（HRcs = 1.10（95% CI = 0.78–1.57））中，SOM 风险在 1-3 和 4-6 HLA-mm 亚组中使用 MTORI 低于非 MTORI，[（ HR = 0.84;（95％CI = 0.71-0.99），和（HR = 0.86; 95％CI = 0.78-0.94）;死亡分别]风险_交流和复合的结果（NMSC或死亡_交流和SOM或死亡_AC）在几乎所有 HLA-mm 亚组中，MTORI 均高于非 MTORI。

结论

MTORIs 与几乎所有 HLA-mm 亚组 ca 中的 NMSC 和 SOM 保护有关；然而，它们与成年肾移植受者全因死亡率增加的关系需要进一步调查。