List of cohorts.

The demand for transplant organs far exceeds the available supply. In the United States alone, more than 90,000 patients are currently on the kidney transplant waitlist, yet only about one third of them will ever receive a transplant. Xenotransplantation, organ transplants from gene edited pigs, offers a potential solution to this shortage. Successful investigational transplants of pig kidneys into brain-dead recipients and expanded access cases involving living human recipients have resulted in the green-lighting of the first human clinical trials. Using the benchmark of 2-year survival of non-human primates in pre-clinical studies, we developed a tool that can identify individual wait-listed patients predicted to have a shorter life expectancy than with a xenotransplant, utilizing Random Survival Forest, DeepSurv and Cox Proportional-Hazards models. We found that it is hard to identify patients that reach clinical equipoise unless the expected xenograft survival exceeds two years, with the Random Survival Forest model identifying less than 5% of such patients. Few patients would benefit based on survival alone and potential beneficiaries are spread across more than 200 transplant centers. Several incentives could allow more patients to reach equipoise. At the same benchmark of 2-year xenograft survival, keeping patients inactive on the waitlist while they have a functioning xeno-kidney increases the percentage achieving equipoise by up to 1.7% across cohorts. Granting patients with failed xenografts the same priority as prior living donors increases this by up to 17.9%, while assigning them the highest priority raises it by up to 28.5%. We are able, however, to identify phenotypes that have a high mortality and low transplant rates in the current allocation system that could serve as acceptable candidates; while not achieving equipoise, they would enjoy the benefits of being dialysis free.

移植器官的需求远大于供给。仅美国一地，目前就有超过9万名患者处于肾脏移植等待队列中，但最终仅约三分之一的患者能够接受移植手术。异种移植（Xenotransplantation），即源自基因编辑猪的器官移植，为缓解器官短缺问题提供了潜在解决方案。针对脑死亡受体的猪肾脏试验性移植成功，以及涉及活体人类受体的扩大准入病例，推动了首例人类异种移植临床试验的获批。本研究以临床前研究中非人类灵长类动物的2年存活率为基准，利用随机生存森林（Random Survival Forest）、DeepSurv及Cox比例风险（Cox Proportional-Hazards）模型，开发了一款可识别等待队列中预期寿命较接受异种移植更短的患者的工具。研究发现，除非异种移植物的预期存活时间超过2年，否则很难识别达到临床平衡的患者，其中随机生存森林模型仅能识别出不到5%的此类患者。仅基于生存获益而言，能从异种移植中获益的患者寥寥无几，且潜在获益患者分布于200余家移植中心。多项激励策略可帮助更多患者达到临床平衡。在异种移植物2年存活率的同一基准下，当患者拥有功能正常的异种肾脏时，维持其在等待队列中处于非活跃状态，可使各队列中达到临床平衡的患者比例最高提升1.7%。将异种移植失败患者的优先级与既往活体器官捐献者等同，可使该比例最高提升17.9%；若将其优先级设为最高，则可使比例最高提升28.5%。不过，本研究仍可识别出现行分配体系中死亡率高、移植率低的表型人群，这类人群可作为可接受的候选受体；尽管未达到临床平衡，但他们可免于透析治疗，从而获益。