results of two cases of pig-to-human kidney xenotransplantation | NEJM


Abstract

Background

Genetically modified pig xenografts have emerged as one of the most promising solutions to the shortage of human organs available for transplantation. The challenge in this model has been hyperacute rejection. To avoid this, pigs were bred knockout of the alpha-1,3-galactosyltransferase gene and with subcapsular autologous thymic tissue.

Methods

We transplanted kidneys from these genetically modified pigs into two brain-dead human recipients whose circulatory and respiratory activity was maintained on a ventilator for the duration of the study. We performed serial biopsies and monitored urine output and kinetic estimated glomerular filtration rate (eGFR) to assess renal function and xenograft rejection.

Results

The xenograft in both recipients began producing urine within moments of reperfusion. During the 54-hour study, kinetic eGFR increased from 23 ml per minute per 1.73 m2 of body surface area before transplantation at 62 ml per minute per 1.73 m2 after transplantation in recipient 1 and from 55 to 109 ml per minute per 1.73 m2 in recipient 2. In both recipients, the creatinine level, which was at steady state, decreased after implantation of the xenograft, from 1.97 to 0.82 mg per deciliter in the recipient 1 and 1.10 to 0.57 mg per deciliter in recipient 2. The transplanted kidneys remained pink and well perfused, continuing to produce urine throughout the study. Biopsies performed at 6, 24, 48, and 54 hours revealed no evidence of hyperacute or antibody-mediated rejection. Hourly urine output with the xenograft was more than double the output with native kidneys.

conclusion

Genetically engineered kidney xenografts from pigs remained viable and functioned in brain-dead human recipients for 54 hours, with no signs of hyperacute rejection. (Funded by Lung Biotechnology.)


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