Cheungpasitporn Wisit, Lentine Krista L, Tan Jane C, Kaufmann Matthew, Caliskan Yasar, Bunnapradist Suphamai, Lam Ngan N, Schnitzler Mark, Axelrod David A
Mayo Clinic, Rochester, MN, USA.
Saint Louis University, Saint Louis, MO, USA.
Curr Transplant Rep. 2021 Jun;8(2):100-110. doi: 10.1007/s40472-021-00321-6. Epub 2021 Apr 6.
While kidney transplantation improves the long-term survival of the majority of patients with end-stage kidney disease (ESKD), age-related immune dysfunction and associated comorbidities make older transplant recipients more susceptible to complications related to immunosuppression. In this review, we discuss appropriate management of immunosuppressive agents in older adults to minimize adverse events, avoid acute rejection, and maximize patient and graft survival.
Physiological changes associated with senescence can impact drug metabolism and increase the risk of posttransplant infection and malignancy. Clinical trials assessing the safety and efficacy of immunosuppressive agents in older adults are lacking. Recent findings from U.S. transplant registry-based studies suggest that risk-adjusted death-censored graft failure is higher among older patients who received antimetabolite avoidance, mammalian target of rapamycin inhibitor (mTORi)-based, and cyclosporine-based regimens. Observational data suggest that risk-adjusted mortality may be increased in older patients who receive mTORi-based and cyclosporine-based regimens but lower in those managed with T-cell induction and maintenance steroid avoidance/withdrawal.
Tailored immunosuppression management to improve patient and graft survival in older transplant recipients is an important goal of personalized medicine. Lower intensity immunosuppression, such as steroid-sparing regimens, appear beneficial whereas mTORi- and cyclosporine-based maintenance are associated with greater potential for adverse effects. Prospective clinical trials to assess the safety and efficacy of immunosuppression agents in older recipients are urgently needed.
虽然肾移植可提高大多数终末期肾病（ESKD）患者的长期生存率，但与年龄相关的免疫功能障碍及相关合并症使老年移植受者更容易发生与免疫抑制相关的并发症。在本综述中，我们讨论老年患者免疫抑制剂的合理管理，以尽量减少不良事件、避免急性排斥反应，并使患者和移植物生存率最大化。
与衰老相关的生理变化会影响药物代谢，并增加移植后感染和恶性肿瘤的风险。缺乏评估免疫抑制剂在老年患者中安全性和有效性的临床试验。基于美国移植登记研究的最新发现表明，在接受抗代谢物避免、基于雷帕霉素靶蛋白抑制剂（mTORi）和基于环孢素方案的老年患者中，风险调整后的死亡截尾移植物失败率更高。观察性数据表明，接受基于mTORi和基于环孢素方案的老年患者风险调整后的死亡率可能会增加，但接受T细胞诱导和维持性类固醇避免/撤药管理的患者死亡率较低。
量身定制免疫抑制管理以提高老年移植受者的患者和移植物生存率是精准医学的一个重要目标。较低强度的免疫抑制，如类固醇节省方案，似乎有益，而基于mTORi和环孢素的维持治疗不良反应的可能性更大。迫切需要进行前瞻性临床试验来评估免疫抑制剂在老年受者中的安全性和有效性。
