Results of Two Cases of Pig-to-Human Kidney XenotransplantationRobert A. Montgomery, Jeffrey Stern, Bonnie E. Lonze et al.|New England Journal of Medicine|2022 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.).
International Kidney Paired DonationCASE REPORT We report a 10-way domino transplant (Fig. 1), which was initiated in September 2009 and concluded in July 2010. The uniqueness of this chain was that it included the international exchange of kidneys between the United States and Canada. The chain was initiated by an altruistic donor and included three hospitals, four flights, one international exchange, and one pediatric recipient. The international donor and recipient procedures were performed at McGill University (Montreal, Quebec, Canada) and Johns Hopkins University (Baltimore, MD). Both organs were transported via chartered international flights with cold ischemia times of less than 6 hr, which included not only procurement and travel time but also time for customs clearance. Donor-related expenses were charged at the institution where donation occurred.FIGURE 1: Schematic illustration of international domino-paired donation chain. Three institutions participated in this 10-way KPD, which resulted in 10 successful living-donor renal transplants. Intended donor (D)–recipient (R) pairs are depicted on the face of the same domino. Actual donor–recipient pairs are indicated by the colored arrows that correspond to the month of the transplant. The chain was initiated by a nondirected donor (D1) who underwent nephrectomy and donated to the first recipient (R1) on September 8, 2009 at Johns Hopkins (Baltimore, MD). Both international donors were shipped on chartered flights, had less than 7 hr of cold ischemia time, and functioned immediately.Additional arrangements were necessary to account for a newly developed United Network for Organ Sharing (UNOS) policy. UNOS Policy 3.3.7 was implemented shortly before this planned kidney paired donation (KPD). This policy required that all living-donor kidneys be recovered at Organ Procurement and Transplantation Network member centers in the United States (1). We requested a waiver, given the imminent donor procurement date, allowing this KPD to proceed as planned and requested that UNOS revisit this policy, with such international exchanges in mind. To proceed, we were required to provide a detailed list of McGills’ living-donor protocols, along with written proof that we verified that McGill complied with these protocols. Additionally, McGill University agreed to follow the UNOS policy for living-donor follow-up to ensure that the donor care met certain standards. Currently, all recipients are alive with functioning grafts. DISCUSSION Connolly et al. (2) recently highlighted the advantages of international cooperation and organ sharing in KPD. Successful KPD hinges on a sufficient number of donor–recipient pairs to maximize match rates (3–5). This is especially true for broadly sensitized patients who are searching for rare donor genotypes found in large KPD pools (6). Expansion of KPD practices to include international registries would be the most logical way to increase the donor pool. Currently, active KPD registries exist in many countries including the United States, Canada, the United Kingdom, The Netherlands, Korea, and Spain. KPD sharing between Canada and the United States is logistically tenable due to a shared border, language, and relatively short travel distances. In fact, a chartered flight from Baltimore to Montreal is shorter than many of the current flights for live-donor organ transport in other areas of the United States, which have resulted in prompt allograft function (7). Additionally, the American Society of Transplantation, the American Society of Transplant Surgeons, and the Canadian Society of Transplantation share close collaboration and similar philosophical understandings. It seems logical that the transplant centers in the United States and Canada would benefit by combining KPD pools and allowing more patients to be transplanted. We would suggest re-looking at this UNOS policy with revisions in mind to allow for international exchanges with centers that have regulations and mission to that of UNOS. In 2009, we demonstrated the feasibility of international participation in a KPD chain by performing a 10-way exchange starting with a nondirected donor, which included one Canadian donor–recipient pair. Both donor and recipient operations were performed simultaneously, requiring meticulous planning to minimize cold ischemia time while transporting the organs on international flights. Factoring time for customs clearance was something that had not previously been a part of organ transport logistics. Additionally, because this exchange occurred before guidance from the Centers for Medicare & Medicaid Services encouraging donor costs to follow a donated kidney to the recipient hospital, donation costs were directed to the donation center. If this exchange were to happen today, arrangements would need to be made with the international donation center to determine how to handle these expenses. This exchange allowed for both centers to successfully transplant sensitized recipients. In the past two decades, KPD has allowed many highly sensitized patients to identify suitable matches and undergo transplantation, greatly improving their life expectancy, quality of life, and reducing their cost of care (8). New methods to increase KPD pools would only further enhance match rates especially for the most highly sensitized. Expansion of KPD to geographically related countries is the next logical step. The transplant community must act now to remove barriers to a broader implementation of international sharing of KPD lists to further optimize the potential of this modality. Jacqueline M. Garonzik-Wang 1 Brigitte Sullivan1 Janet M. Hiller1 Valerie Cass2 Jean Tchervenkow2 Liane Feldman2 Dana Baran2 Prosanto Chaudhury2 Marcelo Cantarovich2 Dorry L. Segev1,3 Robert A. Montgomery1 1 Division of Transplant Surgery Department of Surgery Johns Hopkins University School of Medicine Baltimore, MD 2 Multi-Organ Transplant Program McGill University Health Center Montreal, Quebec, Canada 3 Department of Epidemiology Johns Hopkins School of Public Health Baltimore, MD
Survey of Transplant-Related Pharmacy Services at Large Comprehensive Transplant Centers in the United StatesCarmelina Staino, John J. Lewin, Todd Nesbit et al.|Progress in Transplantation|2013 CONTEXT: United Network for Organ Sharing (UNOS) 2011 bylaws and Centers for Medicare and Medicaid Services (CMS) regulations require a transplant pharmacist to be an active participant in the care of transplant patients. Transplant centers must be members in good standing with UNOS in order to perform transplants and must be certified by CMS to participate with Medicare. OBJECTIVE: To identify characteristics of transplant-related pharmacy services at comprehensive transplant centers. DESIGN: Survey regarding number of full-time equivalent (FTE) transplant pharmacists relative to number of annual transplants, transplant pharmacy model, roles in inpatient and clinic environments, training and specialization, funding sources, and expansion plans.Participants-Surveys were received from 14 (74%) of 19 identified centers that performed 200 to 400 kidney, liver, pancreas, simultaneous kidney/pancreas, heart, and lung transplants in 2010, representing 55 transplant pharmacists. RESULTS: A mean of 325 transplants were performed in 2010 at the surveyed centers. The mean number of pharmacist FTEs was 4.25, which yielded a transplant-to-pharmacist ratio of 76.5. Nine centers (64%) practiced in a pharmacy specialist-only model, 12 (86%) practiced in a service-based fashion, and 10 (71%) saw patients in clinic. Fifty-four pharmacists (98%) had obtained a PharmD degree, 45 (82%) had completed 1 postgraduate year, and 28 (51%) had completed 2 postgraduate years of training. Nine centers (64%) funded FTEs solely through the pharmacy department. Ten centers (71%) plan to expand transplant pharmacist staff by a mean of 1.4 FTEs. CONCLUSIONS: Large comprehensive transplant centers use multiple transplant pharmacists to perform patient care in the inpatient and outpatient environments. Most centers plan to expand FTEs. Further characterization of transplant pharmacists appears warranted.