Faculty Bibliography

BACKGROUND:Xenografts from genetically modified pigs have become one of the most promising solutions to the dearth of human organs available for transplantation. The challenge in this model has been hyperacute rejection. To avoid this, pigs have been bred with a 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 ventilators for the duration of the study. We performed serial biopsies and monitored the urine output and kinetic estimated glomerular filtration rate (eGFR) to assess renal function and xenograft rejection. RESULTS:in Recipient 2. In both recipients, the creatinine level, which had been at a steady state, decreased after implantation of the xenograft, from 1.97 to 0.82 mg per deciliter in Recipient 1 and from 1.10 to 0.57 mg per deciliter in Recipient 2. The transplanted kidneys remained pink and well-perfused, continuing to make urine throughout the study. Biopsies that were performed at 6, 24, 48, and 54 hours revealed no signs of hyperacute or antibody-mediated rejection. Hourly urine output with the xenograft was more than double the output with the native kidneys. CONCLUSIONS:Genetically modified kidney xenografts from pigs remained viable and functioning in brain-dead human recipients for 54 hours, without signs of hyperacute rejection. (Funded by Lung Biotechnology.).

Donation after circulatory determination of death (DCDD) has increased organ donation rates in the US over the past decade within an established legal framework, which is consistent with and supports individual and family decisions regarding organ donation in the context of end-of-life care. A new application, controlled DCDD donation utilizing thoracoabdominal normothermic regional perfusion (NRP) protocols (cDCDD-NRP), provides the opportunity to maximize a donation decision by recovering additional organs for transplant, including the heart, and to limit the detrimental impact of warm ischemic time by perfusing organs in situ following the declaration of circulatory death. In this viewpoint, we narrate our rationale for why cDCDD-NRP is consistent within the existing legal framework for organ donation in the United States and recommend no changes to the Uniform Determination of Death Act.