Developing personalized immunosuppression for older kidney transplant recipients

为老年肾移植受者开发个性化免疫抑制

• 批准号: 10304934
• 负责人: Mara A. McAdams DeMarco
• 金额: $ 6.49万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-12-18 至 2022-02-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10304934
• 关键词: Accounting; Acute; Age; Allografting; Attenuated; Benefits and Risks; Calcineurin inhibitor; Car Phone; Characteristics; Clinical; Clinical Trials; Communication Tools; Cost Savings; Counseling; Custom; Data; Data Element; Data Set; Databases; Dementia; Diabetes Mellitus; Dose; Elderly; End stage renal failure; Environment; Equilibrium; Fracture; Goals; Graft Survival; Guidelines; Homeostasis; Immune response; Immune system; Immunosuppression; Impairment; Infection; Inpatients; Internet; Kidney Transplantation; Link; Malignant Neoplasms; Measures; Medicare; Medicare claim; Metabolism; Methods; Modernization; Morbidity - disease rate; Outcome; Outpatients; Patients; Pharmaceutical Preparations; Pharmacy facility; Physicians; Physiological; Pneumonia; Population; Probability; Protocols documentation; Records; Regimen; Registries; Reporting; Risk; Sepsis; Serum; Survival Analysis; Testing; Time; Transplant Recipients; Transplantation; Update; Variant; Work; adverse outcome; age group; attenuation; base; blind; comorbidity; comparative cost effectiveness; cost; cost effective; cost effectiveness; data registry; dementia risk; frailty; markov model; mortality; novel; personalized approach; personalized medicine; prevent; response; transplant registry

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. !

抽象的 > 400,000名老年人（年龄≥55岁）患有末期肾脏疾病（ESRD）。有5倍 该年龄段的肾脏移植数量（KT）增加。由于 体内稳态受损，合并症较高和免疫系统衰减。这些生理因素 影响年长的KT接受者对免疫抑制（IS）药物的反应，这是一种终身治疗。 短期福利与长期不利结果之间的平衡可能会在较旧的情况下受到质疑 KT收件人。出色的短期结局（1年同种异体生存> 95％和急性排斥[AR] <15％）是 在现代患者IS的年轻患者中取得了成就，但我们的初步发现表明，年龄较大 在1.5倍时，较差的风险是公差。年长的KT收件人也更容易受到长期对立的影响 与现代相关的结果是感染，恶性肿瘤和新发育糖尿病等方案 移植（NODAT）由衰减的免疫响应部分产生。我们的初步发现 表明，钙调神经酶抑制剂的方案会增加老年受体的痴呆症风险。但是，我们的 初步数据表明这不是个性化的；中心实践占IS IS方案变异的46％。 尽管已经发现KT可以节省ESRD患者的成本，但KT总成本受积累的影响 该人群中的长期不利结果。不是在成本盲的环境中选择；如果有风险 收益相似，然后成本效益是一个重要的IS IS疗法选择。风险， 对年长的KT接收者的收益和成本效益不能简单地从对年轻人的研究中推断出来 接受者或大部分排除老年接受者的临床试验。具有所有密钥的综合数据集 开发个性化需要数据元素适用于较老的KT收件人。 为了开发一种个性化方法是针对年长的KT收件人，我们将将3个新颖数据集集成 > 78,800名年长的KT接收者KT接收者（2005-2019）：（1）来自科学注册表的国家数据 移植受者（SRTR）； （2）Medicare声称确定KT后的结果和成本； （3）药房 声称不仅要识别代理，而且还代谢的新型实验室数据是水平（对于14,000年级来说 收件人）。使用此集成数据，我们将：1）比较IS IS方案对有效性，发病率， 和年龄较大的KT接受者的死亡率； 2）开发马尔可夫模型并计算IS的成本效益 老年KT接受者的方案； 3）产生有关预测效率，发病率和的个性化报告 死亡率以及从业者使用的疗法成本，用于用于老年KT接受者的临床咨询。 我们的目标是提供证据和沟通工具，以帮助将移植领域移开 基于中心的协议是针对年长的KT收件人。预测AR权衡的能力 对于特定的长期不良结果，嫁接生存率是较老的KT接受者的方案，将允许 可以定制的患者和医生是以具有成本效益，更明智的方式进行选择。 呢