The recent report of the first pig kidney transplant in a living human brings hope to thousands of people with end‐stage kidney failure. The scientific community views this early success with caution as kidney xenotransplantation exhibits many challenges and barriers. One of these is coagulation dysregulation. This includes (i) pig von Willebrand Factor (vWF) interaction with human platelets, which can induce abnormal clotting responses, heightening the risk of graft failure, (ii) the inefficiency of pig thrombomodulin in activating human protein C, which emphasizes the species‐specific variations that aggravate coagulation challenges, and (iii) the development of thrombotic microangiopathy in the pig grafts and the occurrence of systemic consumptive coagulopathy in the recipients. Indeed, coagulation dysregulation largely results from differences in endothelial cell response and incompatibilities between pig and human coagulation–anticoagulation pathways. These barriers can be resolved by modifications to pig vWF and the expression of human thrombomodulin and endothelial protein C receptors in pig cells, serving as strategic interventions to align the coagulation systems of the two species more closely. These coagulation challenges have clinical implications in how they affect graft survival and patient outcome. Genetic engineering of the organ‐source pig and the administration of various drugs have assisted in correcting this coagulation dysregulation. Hence, comprehending and controlling coagulation dysregulation is crucial for progress in xenotransplantation as a viable option for treating patients with terminal kidney disease.

中文翻译：

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描述肾异种移植后人类和非人灵长类动物的凝血反应——叙述性综述


最近报道了首例活体猪肾移植手术，为成千上万的终末期肾衰竭患者带来了希望。科学界对这一早期成功持谨慎态度，因为肾异种移植表现出许多挑战和障碍。其中之一是凝血功能障碍。这包括 （i） 猪血管性血友病因子 （vWF） 与人血小板的相互作用，可诱导异常凝血反应，增加移植物失败的风险，（ii） 猪血栓调节蛋白在激活人蛋白 C 方面的效率低下，这强调了加剧凝血挑战的物种特异性变异，以及 （iii） 猪移植物中血栓性微血管病的发展和受体中全身性消耗性凝血病的发生。事实上，凝血功能障碍主要是由于内皮细胞反应的差异以及猪和人凝血-抗凝途径之间的不相容性造成的。这些障碍可以通过修饰猪 vWF 以及猪细胞中人血栓调节蛋白和内皮蛋白 C 受体的表达来解决，作为战略干预措施，使两个物种的凝血系统更紧密地对齐。这些凝血挑战在如何影响移植物存活和患者预后方面具有临床意义。器官来源猪的基因工程和各种药物的施用有助于纠正这种凝血失调。因此，理解和控制凝血功能障碍对于异种移植作为治疗终末期肾病患者的可行选择的进展至关重要。