In vitro studies indicate that kidney transplantation from gene-edited pigs in which expression of all three of the known glycan xenoantigens has been deleted may be more challenging in nonhuman primates (NHPs) than it will be in human recipients. Furthermore, pig-to-human xenotransplantation offers several other advantages - (i) the patient can communicate with the surgical team; (ii) recipient microbiological monitoring and environment will be clinical-grade; and (iii) sophisticated graft monitoring and imaging techniques, (v) therapeutic interventions, e.g., dialysis, plasmapheresis, and (v) intensive care can be deployed that are not easily available in NHP laboratory models. We suggest, therefore, that progress to develop safe, informative human clinical trials will be accelerated if pilot clinical cases are initiated. The selection of patients for kidney xenotransplantation can include those who are at high risk of dying imminently, e.g., those experiencing increasing vascular access challenges with no realistic alternative therapy available, and those who have been accepted onto the waitlist for an allograft, but who are unlikely ever to receive one. Patients with an increased risk of dying include those with (i) age >60 years, (ii) blood groups O or B, and (iii) diabetic nephropathy. UNOS data indicate that an average of 25 patients on the kidney waitlist in the USA die or are removed from the list every day (i.e., >9,000 each year). Given the improved xenograft survival observed in preclinical studies, we suggest that it is time to plan a small pilot clinical trial for healthy dialysis patients who understand the risks and potential benefits of kidney xenotransplantation.

中文翻译：

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时机已经到来：启动猪肾异种移植试点临床试验的案例。


体外研究表明，所有三种已知聚糖异种抗原的表达均已被删除的基因编辑猪的肾移植在非人灵长类动物 (NHP) 中可能比在人类受体中更具挑战性。此外，猪到人的异种移植还具有其他几个优点 - (i) 患者可以与手术团队沟通； (ii) 接受者微生物监测和环境将达到临床级； (iii) 先进的移植物监测和成像技术，(v) 治疗干预，例如透析、血浆置换，以及 (v) 重症监护，这些在 NHP 实验室模型中不易实现。因此，我们建议，如果启动试点临床案例，将加快开发安全、信息丰富的人体临床试验的进展。肾异种移植患者的选择可以包括那些面临即将死亡的高风险的患者，例如，那些经历越来越多的血管通路挑战而没有可用的现实替代疗法的患者，以及那些已被接受进入同种异体移植等候名单但仍处于死亡状态的患者。不太可能收到一份。死亡风险增加的患者包括 (i) 年龄 >60 岁、(ii) 血型 O 或 B 以及 (iii) 糖尿病肾病的患者。 UNOS 数据表明，美国每天平均有 25 名肾脏候补名单上的患者死亡或从名单中删除（即每年 >9,000）。鉴于临床前研究中观察到的异种移植存活率有所提高，我们建议现在是时候为了解肾异种移植的风险和潜在益处的健康透析患者计划一项小型试点临床试验了。