Patient Oriented Research in Solid Organ Transplantation

总结 美国目前有超过10万名患者等待实体器官移植，但没有足够的器官可供保存 这些病人从等待名单死亡。安全地扩大捐助者库，并将捐助者与捐助者进行最佳匹配。 正确的受体是移植的关键申请人的首要目标是指导临床决策- 实体器官移植的决策和政策，特别是在艾滋病毒等新扩张的背景下， 受感染的捐赠者和接受者，扩大活体捐赠的标准，以及免疫不相容性。 这是一个K24中期职业生涯研究者奖Dorry Segev，医学博士，博士，移植的更新建议 约翰霍普金斯大学的外科医生和流行病学家，发表了422篇论文，并获得了4项NIH R 01和2 NIH U 01奖在他的12年的教师。K24的前5年提供了保护时间， Segev博士需要指导11名住院医生，16名医学生，5名研究生和14名初级教师 在一个令人兴奋的，富有成效的多学科环境;这些学员写了141第一作者的论文， 博士Segev的直接指导，并收到31 NIH/AHRQ赠款和13基金会赠款。此次更新将 利用Segev博士通过NIH资助的 研究，包括（1）将国家移植供体和受体登记数据与保险联系起来， （2）超过5500例活体供肾者的纵向多中心研究;（3） HLA颗粒不相容性活体供肾移植的长期预后和生存率 和超过2000名受体及其供体的抗体数据;和（4）一项关于虚弱的前瞻性多中心研究， 健康素养，认知功能障碍，生物标志物和其他新的风险预测因子，超过5000个肾脏 2000例肝移植患者此外，这次续约将利用两个新的U 01资助的 艾滋病毒对艾滋病毒肾和肝移植的研究，包括艾滋病毒相关并发症的测量， HIV相关肾脏疾病的特征，HIV重叠感染的测量，以及 潜伏感染的HIV前病毒群体的大小和遗传组成。 这些国家数据和大型多中心队列研究为辅助研究提供了丰富的基础， 学员，以及许多先进的方法培训的机会。具体而言，这一新目标 K24是：（1）为了更好地了解接受肝移植的HIV+患者的生存益处，使用 新的联系，以确定艾滋病毒患者的LT等候名单上的处方填写特定的艾滋病毒药物 治疗;（2）描述长期献血后eGFR轨迹和与随后的 活体供肾者的结果;（3）确定近期致敏患者的适当治疗方法， 死者捐赠者分配和肾脏交换的时代;和（4）扩大博士的能力。 下一代实体器官移植的临床科学家。

Summary Over 100,000 patients in the US currently await solid organ transplantation, with inadequate organs to save these patients from waitlist mortality. Safely expanding the donor pool, and optimally matching donors to the right recipient, is essential to transplantation. The overarching goal of the applicant is to guide clinical decision- making and policy in solid organ transplantation, particularly in the context of novel expansions such as HIV- infected donors and recipients, expanded criteria for living donation, and immunological incompatibility. This is a renewal proposal for a K24 Midcareer Investigator Award for Dorry Segev, MD, PhD, a transplant surgeon and epidemiologist at Johns Hopkins University who has published 422 papers and received 4 NIH R01 and 2 NIH U01 awards in his 12 years on faculty. The first 5 years of this K24 provided the protected time that Dr. Segev needed to mentor 11 residents, 16 medical students, 5 graduate students, and 14 junior faculty in an exciting, productive multidisciplinary environment; these mentees wrote 141 first-authored papers under Dr. Segev’s direct mentorship, and received 31 NIH/AHRQ grants and 13 foundation grants. This renewal will leverage carefully designed cohorts and data-driven tools that Dr. Segev has generated through NIH-funded studies, including (1) a linkage of national transplant donor and recipient registry data to insurance and pharmacy claims; (2) a longitudinal multicenter study of over 5500 living kidney donors; (3) multicenter study of long-term outcomes and survival benefit from incompatible live donor kidney transplantation, with granular HLA and antibody data on over 2000 recipients and their donors; and (4) a prospective multicenter study of frailty, health literacy, cognitive dysfunction, biomarkers, and other novel risk predictors, with over 5000 kidney transplant and 2000 liver transplant patients. In addition, this renewal will leverage two new U01-funded studies of HIV-to-HIV kidney and liver transplantation, including measurement of HIV-related complications, characterization of HIV-related kidney disease, measurement of HIV superinfection, and examination of the size and genetic composition of the latently infected HIV proviral population. These national data and large multicenter cohort studies provide rich substrate for ancillary studies by mentees, as well as many opportunities for advanced methodologic training. Specifically, the new aims of this K24 are: (1) to better understand survival benefit in HIV+ patients undergoing liver transplantation, using a novel linkage to identify patients with HIV on the LT waitlist by prescription fills of medications specific to HIV treatment; (2) to characterize long-term post-donation eGFR trajectories and associations with subsequent outcomes in living kidney donors; (3) to identify the appropriate treatment for sensitized patients in the recent era of deceased donor allocation and kidney exchange; and (4) to expand Dr. Segev’s capacity to mentor the next generation of clinician-scientists in solid organ transplantation.