Details

Autor(en) / Beteiligte

• Firl, Daniel J.
• Markmann, James F.

Titel

Measuring success in pig to non‐human‐primate renal xenotransplantation: Systematic review and comparative outcomes analysis of 1051 life‐sustaining NHP renal allo‐ and xeno‐transplants

Ist Teil von

• American journal of transplantation, 2022-06, Vol.22 (6), p.1527-1536

Ort / Verlag

United States: Wiley Subscription Services, Inc

Erscheinungsjahr

2022

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• Facile gene editing has accelerated progress in pig to non‐human‐primate (NHP) renal xenotransplantation, however, outcomes are considered inferior to NHP‐allotransplantation. This systematic review and outcomes analysis of life‐sustaining NHP‐renal transplantation aimed to benchmark “preclinical success” and aggregated 1051 NHP‐to‐NHP or pig‐to‐NHP transplants across 88 articles. Although protocols varied, NHP‐allotransplantation survival (1, 3, 12months, 67.5%, 37.1%, 13.2%) was significantly greater than NHP‐xenotransplantation (1, 3, 12 months, 38.8%, 14.0%, 4.4%; p < .001); a difference partially mitigated by gene‐edited donors containing at least knockout of alpha‐1,3‐galactosyltransferase (1, 3, 12 months, 47.1%, 24.2%, 7.6%; p < .001). Pathological analysis demonstrated more cellular rejection in allotransplantation (62.8% vs. 3.1%, p < .001) and more antibody‐mediated rejection in xenotransplantation (6.8% vs. 45.5%, p < .001). Nonrejection causes of graft loss between allotransplants and xenotransplants differed; infection and animal welfare (1.7% vs. 11.2% and 3.9% vs. 17.0%, respectively, p < .001 for both). Importantly, even among a subgroup of unsensitized rhesus macaques under long‐term immunosuppression, NHP‐allotransplant survival was significantly inferior to clinical allotransplantation (6 months, 36.1% vs. 94.0%; p < .001), which suggests clinical outcomes with renal xenografts may be better than predicted by current preclinical data. A systematic review and comparative outcomes analysis of life‐sustaining non‐human‐primate (NHP) kidney transplantation shows a survival gradient, highest for NHP‐to‐NHP allotransplantation, lowest for pig‐to‐NHP xenotransplantation, and intermediate for gene‐edited pig‐to‐NHP xenotransplantation.