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.).

Transplanting hepatitis C viremic donor organs into hepatitis C virus (HCV)-negative recipients is becoming increasingly common; however, practices for posttransplant direct-acting antiviral (DAA) treatment vary widely. Protracted insurance authorization processes for DAA therapy often lead to treatment delays.

Antibody responses among immunocompromised solid organ transplant recipients (SOT) infected with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) may be diminished compared to the general population and have not been fully characterized. We conducted a cohort study at our transplant center to investigate the rate of seroconversion for SARS-CoV-2 IgG antibodies among SOT recipients who were diagnosed with Coronavirus disease 2019 (COVID-19) and underwent serum SARS-CoV-2 IgG enzyme-linked immunosorbent assay (ELISA) testing. The 61 patients who were included in the final analysis underwent initial SARS-CoV-2 IgG testing at a median of 62 days (Interquartile range 55.0-75.0) from symptom onset. Note that, 51 of 61 patients (83.6%) had positive SARS-CoV-2 IgG results, whereas 10 (16.4%) had negative IgG results. Six (60%) out of 10 seronegative patients underwent serial IgG testing and remained seronegative up to 17 weeks post-diagnosis. Use of belatacept in maintenance immunosuppression was significantly associated with negative IgG antibodies to SARS-CoV-2 both in univariate and multivariate analyses (Odds ratio 0.04, p = .01). In conclusion, the majority of organ transplant recipients with COVID-19 in our study developed SARS-CoV-2 antibodies. Further longitudinal studies of the durability and immunologic role of these IgG responses and the factors associated with lack of seroconversion are needed.

The current kidney allocation system (KAS) preferentially allocates kidneys from blood type A2 or A2B (A/A2B) donors to blood type B candidates. We used national data to evaluate center-level performance of A2/A2B to B transplants, and organ procurement organization (OPO) reporting of type A or AB donor subtyping, in 5-year time periods prior to (2009-2014) and following (2015-2019) KAS implementation. The number of centers performing A2/A2B to B transplants increased from 17 pre-KAS to 76 post-KAS, though this still represents only a minority of centers (7.3% pre-KAS and 32.6% post-KAS). For high-performing centers, the median net increase in A2/A2B to B transplants was 19 cases (range -2-72) per center in the 5 years post-KAS. The median net increase in total B recipient transplants was 21 cases (range -17-119) per center. Despite requirements for performance of subtyping, in 2019 subtyping was reported on only 56.4% of A/AB donors. This translates into potential missed opportunities for B recipients, and even post-KAS up to 2322 A2/A2B donor kidneys may have been allocated for transplantation as A/AB. Further progress must be made both at center and OPO levels to broaden implementation of A2/A2B to B transplants for the benefit of underserved recipients.