Developing personalized immunosuppression for older kidney transplant recipients

摘要 400,000名老年人(年龄55岁，≥)患有终末期肾病。已经有了5倍的 这一年龄段的肾移植(KT)数量增加。年长的收件人是一个不同的群体，因为 动态平衡受损，共病负担增加，免疫系统减弱。这些生理因素 影响老年KT受者对免疫抑制(IS)药物的反应，这是一种终身治疗。 在老年人中，IS的短期好处和长期不良后果之间的平衡可能是具有挑战性的 KT收件人。良好的短期结果(同种异体移植物1年存活率95%和急性排斥反应15%)是 在患有现代IS的年轻患者中实现，但我们的初步研究结果表明，老年KT接受者 在1.5倍的情况下，贫穷的风险增加是耐受性。年龄较大的KT受者也更容易受到长期不良反应的影响 与现代IS方案相关的结果，如感染、恶性肿瘤和新发的糖尿病 移植(NODAT)的部分原因是免疫反应减弱。我们的初步调查结果 提示使用钙调神经磷酸酶抑制剂的IS方案会增加老年接受者患痴呆症的风险。然而，我们的 初步数据表明，IS不是个性化的；中心实践占IS方案变化的46%。 虽然KT已被发现为终末期肾病患者节省了成本，但KT的总成本受到累积的影响 IS在这一人群中的长期不良后果。IS不是在成本盲目的环境中选择的；如果风险 而且益处相似，那么成本效益是IS方案选择的一个重要辅助因素。风险， 老年KT受者的益处和成本效益不能简单地从年轻患者的研究中推断出来 受者或来自基本上排除老年受者的临床试验。包含所有关键字的全面数据集 为年长的KT收件人开发个性化IS需要数据元素。 为了为年长的KT接受者开发个性化的IS方法，我们将集成3个新的数据集 &gt；78,800名老年KT获奖者KT获奖者(2005-2019年)：(1)来自科学登记处的国家数据 移植接受者(SRTR)；(2)医疗保险声称确定KT后的结果和成本；(3)药房 声称不仅要识别使用的试剂，还要确定新陈代谢的IS水平的实验室数据(适用于14,000名较老的人 收件人)。使用这些综合数据，我们将：1)比较IS方案在疗效、发病率、 和老年KT接受者的死亡率；2)建立马尔可夫模型并计算IS的成本效益 老年KT受者的方案；以及3)生成预测疗效、发病率和 死亡率以及用于老年KT接受者临床咨询的IS方案成本。 我们的目标是提供证据和沟通工具，帮助将移植领域从 为年长的KT收件人提供基于中心的IS到个性化IS的协议。预测AR中的取舍能力 在老年KT受者中，针对特定IS方案的移植物存活率和长期不良后果将允许 患者和医生以更具成本效益和更知情的方式定制IS选择。 好了！

ABSTRACT >400,000 older adults (age ≥55) suffer from end-stage renal disease (ESRD). There has been a 5-fold increase in the number of kidney transplants (KT) in this age group. Older recipients are a distinct group due to impaired homeostasis, higher comorbidity burden, and immune system attenuation. These physiologic factors influence older KT recipients’ response to immunosuppression (IS) medications, a lifelong treatment. The balance between short-term benefits and long-term adverse outcomes of IS can be challenging in older KT recipients. Excellent short-term outcomes (1-year allograft survival>95% and acute rejection [AR]<15%) are achieved in younger patients with modern IS, but our preliminary findings suggest that older KT recipients are at 1.5x increased risk of poor IS tolerance. Older KT recipients are also more susceptible to long-term adverse outcomes associated with the modern IS regimens like infections, malignancy, and new-onset diabetes after transplantation (NODAT) resulting in part from an attenuated immune response. Our preliminary findings suggest that IS regimens with calcineurin inhibitors increase an older recipient’s dementia risk. Yet, our preliminary data suggest that IS is not personalized; center practices account for 46% of IS regimen variation. While KT has been found to be cost saving for ESRD patients, the total KT cost is influenced by accumulating long-term adverse outcomes of IS in this population. IS is not chosen in a cost-blind environment; if the risks and benefits are similar, then cost-effectiveness is an important adjunct to IS regimen choice. The risks, benefits, and cost-effectiveness for an older KT recipient cannot simply be inferred from studies of younger recipients or from clinical trials that largely excluded older recipients. A comprehensive dataset with all key data elements is needed to develop personalized IS for older KT recipients. To develop a personalized approach to IS for older KT recipients, we will integrate 3 novel datasets with >78,800 older KT recipients KT recipients (2005-2019): (1) national data from the Scientific Registry of Transplant Recipients (SRTR); (2) Medicare claims to identify post-KT outcomes and costs; (3) pharmacy claims to identify not only IS agents used but also novel lab data of metabolized IS levels (for 14,000 older recipients). Using this integrated data, we will: 1) compare the effects of IS regimens on efficacy, morbidity, and mortality for older KT recipients; 2) develop Markov models and calculate cost-effectiveness for IS regimens for older KT recipients; and 3) generate individualized reports of predicted efficacy, morbidity, and mortality along with IS regimen cost for practitioners to use for the clinical counseling of older KT recipients. Our goal is to provide evidence and communication tools to help move the field of transplantation away from center-based protocols for IS to personalized IS for older KT recipients. The ability to predict trade-offs in AR and graft survival against long-term adverse outcomes for specific IS regimens in older KT recipients will allow patients and physicians to customize IS choices in a cost-effective and more informed manner. !