Recent progress in the pig-to-nonhuman primate kidney transplantation model: Report of a symposium

Three excellent presentations at an industry-sponsored symposium at the (virtual) congress of the combined IXA/CTRMS (September 23-25, 2021) were directed to the value and limitations of the pig-to-nonhuman primate (NHP) kidney transplantation model. Daniel Firl and James Markmann provided a meta-analysis comparing the results of kidney allotransplantation and xenotransplantation in NHPs during the past 25 years. Remarkably, the authors had identified 73 published reports that included 910 individual experiments. Although recipient survival after allotransplantation was longer, the superiority over the survival of xenografts was less than anticipated. Given the excellent short- and medium-term results of clinical kidney allotransplantation today, these data provide hope that the results of clinical pig kidney xenotransplantation may prove significantly better than in NHPs. The authors identified several factors that were shown to statistically influence the success or failure of xenotransplantation. Jean Kwun provided valuable information relating to the longstanding question of whether the survival of a pig organ would be jeopardized if transplanted into an allosensitized recipient. He demonstrated that pig kidney transplantation in an HLA-sensitized patient may be at a disadvantage, although multiple genetic engineering of the organ-source pig significantly delayed rejection. In the initial clinical trials, therefore, it would seem wise to exclude any patient with evidence of anti-HLA antibodies. Andrew Adams reported longer survival (>1 year) of Rhesus monkeys with life-supporting pig kidney grafts than has been achieved previously. Although not consistently achieved, these excellent results were obtained with an anti-CD154mAb-based regimen after CD4⁺ T cell and partial CD20⁺ B cell depletion. Factors that might have contributed to this success, including the phenotype of the pig, the species of the recipient, the recipient's anti-pig antibody level, and the immunosuppressive regimen, were discussed. Importantly, pig kidney function appeared to be normal in long-term surviving monkeys. Each study contributed to our goal of introducing xenotransplantation into the clinic.