Choosing Immune Suppression in Renal Transplantation by Efficacy and Morbidity

根据疗效和发病率选择肾移植中的免疫抑制

• 批准号: 9529611
• 负责人: Vikas R. Dharnidharka
• 金额: $ 36.38万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-18 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9529611
• 关键词: Acute; African American; Allografting; Car Phone; Caucasians; Cessation of life; Characteristics; Clinical; Communication Tools; Comorbidity; Custom; Data; Data Linkages; Data Set; Databases; Decision Making; Diabetes Mellitus; Dialysis procedure; Dose; Drug Combinations; Environment; Equilibrium; Evaluation; Event; Food and Drug Administration Drug Approval; Graft Survival; Immunologics; Immunosuppression; Immunosuppressive Agents; Incidence; Infection; Institutes; Internet; Kidney Failure; Kidney Transplantation; Lead; Link; Lymphoma; Maintenance; Malignant Neoplasms; Measures; Medical; Medical Care Costs; Medicare; Medicare claim; Modeling; Morbidity - disease rate; Mycophenolate; Organ; Organ Donor; Organ Procurements; Organ Transplantation; Outcome; Outcomes Research; Patient risk; Patients; Pharmaceutical Preparations; Pharmacy facility; Physicians; Pneumonia; Pregnancy; Probability; Procedures; Protocols documentation; Race; Randomized Controlled Trials; Regimen; Registries; Reporting; Research; Risk; Safety; Sepsis; Specialist; Subgroup; Survival Rate; Tacrolimus; Time; Toxic effect; Transplant Recipients; Transplantation; Update; Urinary tract infection; Weight; base; blind; clinically relevant; cohort; cost; cost effective; cost effectiveness; data registry; data resource; design; dosage; experience; follow-up; high risk; markov model; novel; novel strategies; organ procurement transplantation network; patient oriented; personalized predictions; prevent; programs; public health relevance; randomized trial; survival outcome; tool; transplant database

DESCRIPTION (provided by applicant): Kidney transplant (KTx) professionals have many choices of immunosuppressive (IS) medications and regimens for their patients. With early acute rejection (AR) rates now low and short term graft survival high, individualized long-term graft survival depends on patients' underlying co-morbidities or complications of IS medications. Yet few studies or data exist on how to balance the trade-offs between IS efficacy (in preventing AR) versus complications, including infections, cancers and new onset diabetes after transplant (NODAT). Randomized trials or FDA-sanctioned Risk Evaluation and Mitigation Strategies help with very specific situations; but along with prior analyses of large national databases, also have many limitations. In this study, we propose to use a novel, three-database linkage of the a) U.S.A. national Organ Procurement and Transplant Network (OPTN) registry: recording initial data on all KTx and subsequent survival outcomes, b) a Medicare billing claims database: covers the first 3 years post-KTx, and c) a national Pharmacy Clearinghouse Database (PCD) that covers 60% of all medication fills in the U.S.A. Using this integration, we can minimize limitations of prior approaches to develop accurate, longitudinal, national level data on the transplant procedures, IS use, survival and non-fatal morbidity. Our investigative team of KTx specialists, economists and statisticians, all with transplant database and outcomes research expertise, can then assess in a more rigorous way than previously possible, the efficacy and morbidity tradeoffs of the IS regimens and doses. In the proposed CISTEM study (Choosing Immune Suppression in Renal Transplantation by Efficacy and Morbidity), we will complete the following three aims: 1) To construct a novel linkage of data from the OPTN registry, an updated Medicare claims dataset and the PCD to quantify the associations of KTx IS with outcome metrics of efficacy and morbidity, adjusted for demographic, medical and immunologic parameters; through propensity-score and covariate-adjusted survival models that will quantify the association between IS regimen or dose and specific measures of efficacy (AR) or morbidity (major infections, cancers, NODAT) that contribute to the hard outcomes of graft survival and patient survival, with sub-analyses for key racial and high-risk subgroups; 2) To use the transition probabilities of events, generated in aim 1, to develop Markov models and calculate the overall cost-effectiveness, including trade-off costs, for each of the major IS regimens in use, by overall group and in the key sub-groups mentioned above; and 3) To use the decision analytics from Aims 1 and 2 to generate individualized and real-time reports of the predicted efficacy/complications outcomes and costs of different KTx IS regimens through a free and updateable patient-focused web- or mobile phone-based risk engine and communication tool. The long-term significance is that physicians and patients will be able to make IS choices in a more cost-effective and better informed manner than any other strategy currently available.

描述（由申请人提供）：肾移植（KTx）专业人员为患者提供多种免疫抑制（IS）药物和治疗方案。随着早期急性排斥反应（AR）率的降低和短期移植物存活率的提高，个体化的长期移植物存活率取决于患者的潜在合并症或IS药物的并发症。然而，关于如何平衡IS功效（预防AR）与并发症（包括感染、癌症和移植后新发糖尿病（NODAT））之间的权衡，几乎没有研究或数据。随机试验或FDA批准的风险评估和缓解策略有助于非常具体的情况;但沿着先前对大型国家数据库的分析， 很多限制。 在这项研究中，我们建议使用一种新的三个数据库链接：a）美国国家器官采购和移植网络（OPTN）登记处：记录所有KTx和随后生存结果的初始数据，B）医疗保险账单索赔数据库：涵盖了KTx后的前3年，以及c）覆盖美国所有药物填充的60%的国家药房交换所数据库（PCD）。使用该集成，我们可以最小化现有方法的限制，关于移植手术、IS使用、生存率和非致死性发病率的国家级纵向数据。我们的KTx专家，经济学家和统计学家的调查团队，都具有移植数据库和结果研究专业知识，然后可以以比以前更严格的方式评估IS方案和剂量的疗效和发病率权衡。在拟议的CISTEM研究中，（通过疗效和发病率选择肾移植中的免疫抑制），我们将完成以下三个目标：1）构建来自OPTN登记处、更新的医疗保险索赔数据集和PCD的数据的新链接，以量化KTx IS与疗效和发病率的结果指标的关联，针对人口统计学、医学和免疫学参数进行调整;通过倾向评分和协变量校正的生存模型，量化IS方案或剂量与疗效（AR）或发病率的特定指标之间的相关性（主要感染，癌症，NODAT），有助于移植物生存和患者生存的硬结果，对关键种族和高风险亚组进行亚组分析; 2）使用目标1中产生的事件转移概率，建立马尔可夫模型，并按总体组和上述关键分组计算使用中的每种主要体制建设方案的总体成本效益，包括权衡成本;和3）使用目标1和2的决策分析，通过免费和可更新的以患者为中心的网络或移动的电话，生成不同KTx IS方案的预测疗效/并发症结局和成本的个性化和实时报告。基于风险引擎和沟通工具。长期意义在于，医生和患者将能够以比目前可用的任何其他策略更具有成本效益和更明智的方式做出IS选择。

项目成果

Impacts of center and clinical factors in antihypertensive medication use after kidney transplantation.

中心和临床因素对肾移植术后降压药物使用的影响。

• DOI: 10.1111/ctr.13803
• 发表时间: 2020
• 期刊: Clinical transplantation
• 影响因子: 2.1
• 作者: Koraishy,FarrukhM;Yamout,Hala;Naik,AbhijitS;Zhang,Zidong;Schnitzler,MarkA;Ouseph,Rosemary;Lam,NganN;Dharnidharka,VikasR;Axelrod,David;Hess,GregoryP;Segev,DorryL;Kasiske,BertramL;Lentine,KristaL
• 通讯作者: Lentine,KristaL

Economic Impacts of ABO-Incompatible Live Donor Kidney Transplantation: A National Study of Medicare-Insured Recipients.

• DOI: 10.1111/ajt.13616
• 发表时间: 2016-05
• 期刊: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
• 作者: Axelrod D;Segev DL;Xiao H;Schnitzler MA;Brennan DC;Dharnidharka VR;Orandi BJ;Naik AS;Randall H;Tuttle-Newhall JE;Lentine KL
• 通讯作者: Lentine KL

Long-term Effects of Gastric Acid Prophylaxis in Kidney Transplant Recipients.

胃酸预防对肾移植受者的长期影响。

• 发表时间: 2023
• 期刊: Revista de nefrologia, dialisis y transplante : publicacion conjunta de la Asociacion Regional de Dialisis y Trasplantes Renales de Capital Federal y Provincia de Buenos Aires y la Sociedad Argentina de Nefrologia
• 作者: Yazici,Halil;Oto,OzgurAkin;Mirioglu,Safak;Dirim,AhmetBurak;Demir,Erol;Uludag,Omer;Akardere,OmerFaruk;Caliskan,Yasar;Lentine,KristaL
• 通讯作者: Lentine,KristaL

Liver targeted therapies for hepatocellular carcinoma prior to transplant: contemporary management strategies.

移植前肝细胞癌的肝脏靶向治疗：当代管理策略。

• DOI: 10.15761/gos.1000171
• 发表时间: 2018
• 期刊: Global surgery (London)
• 作者: Nazzal,Mustafa;Gadani,Sameer;Said,Abdullah;Rice,Mandy;Okoye,Obi;Taha,Ahmad;Lentine,KristaL
• 通讯作者: Lentine,KristaL

Differential risks for adverse outcomes 3 years after kidney transplantation based on initial immunosuppression regimen: a national study.

• DOI: 10.1111/tri.12850
• 发表时间: 2016-11
• 期刊: Transplant international : official journal of the European Society for Organ Transplantation
• 作者: Dharnidharka VR;Schnitzler MA;Chen J;Brennan DC;Axelrod D;Segev DL;Schechtman KB;Zheng J;Lentine KL
• 通讯作者: Lentine KL