Patients with ESKD who would benefit from a kidney transplant face a critical and continuing shortage of kidneys from deceased human donors. As a result, such patients wait a median of 3.9 years to receive a donor kidney, by which time approximately 35% of transplant candidates have died while waiting or have been removed from the waiting list. Those of blood group B or O may experience a significantly longer waiting period. This problem could be resolved if kidneys from genetically engineered pigs offered an alternative with an acceptable clinical outcome. Attempts to accomplish this have followed two major paths: deletion of pig xenoantigens, as well as insertion of "protective" human transgenes to counter the human immune response. Pigs with up to nine genetic manipulations are now available. In nonhuman primates, administering novel agents that block the CD40/CD154 costimulation pathway, such as an anti-CD40 mAb, suppresses the adaptive immune response, leading to pig kidney graft survival of many months without features of rejection (experiments were terminated for infectious complications). In the absence of innate and adaptive immune responses, the transplanted pig kidneys have generally displayed excellent function. A clinical trial is anticipated within 2 years. We suggest that it would be ethical to offer a pig kidney transplant to selected patients who have a life expectancy shorter than the time it would take for them to obtain a kidney from a deceased human donor. In the future, the pigs will also be genetically engineered to control the adaptive immune response, thus enabling exogenous immunosuppressive therapy to be significantly reduced or eliminated.

中文翻译：

---

临床猪肾脏异种移植：我们有多近？

得益于肾脏移植的ESKD患者将面临死者捐赠者不断严重短缺的肾脏。结果，这类患者等待中位时间为3.9年才能接受供体肾脏，此时约有35％的移植候选者在等待期间死亡或从等待名单中删除。B或O血型的人可能会经历更长的等待时间。如果转基因猪的肾脏提供了可以接受的临床结果的替代方案，则可以解决该问题。尝试实现此目的的途径主要有两条：删除猪异种抗原，以及插入“保护性”人转基因以抵抗人的免疫反应。现在可以进行多达九种基因操作的猪。在非人类的灵长类动物中，施用可阻断CD40 / CD154共刺激途径的新型药物（例如抗CD40 mAb）可抑制适应性免疫反应，从而导致猪肾移植物存活数月而无排斥反应（由于感染并发症而终止实验）。在缺乏先天性和适应性免疫反应的情况下，移植的猪肾脏通常表现出出色的功能。预计将在2年内进行临床试验。我们建议，为预期寿命比从已故人类供体获得肾脏所需时间短的选定患者提供猪肾脏移植是合乎道德的。将来，也将对猪进行基因工程改造，以控制适应性免疫反应，