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用于终末期肾病的猪肾异种移植

Xenotransplantation of a Porcine Kidney for End-Stage Kidney Disease.

作者信息

Kawai Tatsuo, Williams Winfred W, Elias Nahel, Fishman Jay A, Crisalli Kerry, Longchamp Alban, Rosales Ivy A, Duggan Michael, Kimura Shoko, Morena Leela, Borges Thiago J, Tomosugi Toshihide, Karadagi Ahmad, Nakamura Tsukasa, Safa Kassem, Giarraputo Alessia, Avillach Claire T, Patalas Eva D, Smith R Neal, Sachs David H, Cosimi A Benedict, Madsen Joren C, Cooper David K C, Pierson Richard, Perrin Steve, Anand Ranjith P, Chhangawala Sagar, Coscarella Matthew, Daigneault Alexandre, Li Feng, Pearce Owen, Qin Wenning, Serkin William T, Yeung Vincent, Getchell Kristen, Low Susan C, Curtis Michael, Colvin Robert B, Riella Leonardo V

机构信息

Transplant Center, Massachusetts General Hospital, Boston.

Harvard Medical School, Boston.

出版信息

N Engl J Med. 2025 May 15;392(19):1933-1940. doi: 10.1056/NEJMoa2412747. Epub 2025 Feb 7.

Abstract

Xenotransplantation offers a potential solution to the organ shortage crisis. A 62-year-old hemodialysis-dependent man with long-standing diabetes, advanced vasculopathy, and marked dialysis-access challenges received a gene-edited porcine kidney with 69 genomic edits, including deletion of three glycan antigens, inactivation of porcine endogenous retroviruses, and insertion of seven human transgenes. The xenograft functioned immediately. The patient's creatinine levels decreased promptly and progressively, and dialysis was no longer needed. After a T-cell-mediated rejection episode on day 8, intensified immunosuppression reversed rejection. Despite sustained kidney function, the patient died from unexpected, sudden cardiac causes on day 52; autopsy revealed severe coronary artery disease and ventricular scarring without evident xenograft rejection. (Funded by Massachusetts General Hospital and eGenesis.).

摘要

异种移植为器官短缺危机提供了一种潜在的解决方案。一名62岁的长期依赖血液透析的男性,患有长期糖尿病、晚期血管病变且存在明显的透析通路难题,接受了一个经过基因编辑的猪肾,该猪肾有69处基因组编辑,包括删除三种聚糖抗原、使猪内源性逆转录病毒失活以及插入七种人类转基因。该异种移植物立即发挥了功能。患者的肌酐水平迅速且持续下降,不再需要透析。在第8天发生了一次由T细胞介导的排斥反应后,强化免疫抑制逆转了排斥反应。尽管肾功能持续存在,但患者在第52天死于意外的突发心脏原因;尸检显示严重冠状动脉疾病和心室瘢痕形成,未发现明显的异种移植排斥反应。(由马萨诸塞州总医院和eGenesis资助。)

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