Faculty Bibliography

BACKGROUND:Understanding immunogenicity and alloimmune risk following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in kidney transplant recipients is imperative to understanding the correlates of protection and to inform clinical guidelines. METHODS:We studied 50 kidney transplant recipients following SARS-CoV-2 vaccination and quantified their anti-spike protein antibody, donor-derived cell-free DNA (dd-cfDNA), gene expression profiling (GEP), and alloantibody formation. RESULTS:Participants were stratified using nucleocapsid testing as either SARS-CoV-2-naïve or experienced prior to vaccination. One of 34 (3%) SARS-CoV-2 naïve participants developed anti-spike protein antibodies. In contrast, the odds ratio for the association of a prior history of SARS-CoV-2 infection with vaccine response was 18.3 (95% confidence interval 3.2, 105.0, p < 0.01). Pre- and post-vaccination levels did not change for median dd-cfDNA (0.23% vs. 0.21% respectively, p = 0.13), GEP scores (9.85 vs. 10.4 respectively, p = 0.45), calculated panel reactive antibody, de-novo donor specific antibody status, or estimated glomerular filtration rate. CONCLUSIONS:SARS-CoV-2 vaccines do not appear to trigger alloimmunity in kidney transplant recipients. The degree of vaccine immunogenicity was associated most strongly with a prior history of SARS-CoV-2 infection.

In July 2022, the Scientific Registry of Transplant Recipients (SRTR) hosted an innovative, multistakeholder consensus conference to identify information and metrics desired by stakeholders in the transplantation system, including patients, living donors, caregivers, deceased donor family members, transplant professionals, organ procurement organization professionals, payers, and regulators. Crucially, patients, caregivers, living donors, and deceased donor family members were included in all aspects of this conference, including serving on the planning committee, participating in preconference focus groups and learning sessions, speaking at the conference, moderating conference sessions and breakout groups, and shaping the conclusions. Patients constituted 24% of the meeting participants. In this report, we document the proceedings and enumerate 160 recommendations, 10 of which have been highly prioritized. SRTR will use the recommendations to develop new presentations of information and metrics requested by stakeholders to support informed decision-making.

Mycotic pseudoaneurysms are a rare, life-threatening complication after pancreas transplant. There have been limited reports of endovascular treatment of mycotic pseudoaneurysms in pancreas transplant recipients. Herein, we report on a case of a mycotic pseudoaneurysm from Pseudomonas aeruginosa after pancreas transplant. A 53-year-old male recipient underwent an uneventful simultaneous pancreas and kidney transplant. He was readmitted 48 days posttransplant with fevers and rigors. Pan-cultures were performed and broad-spectrum antibiotics were initiated. Imaging studies demonstrated a large mycotic pseudoaneurysm arising from the right common iliac artery adjacent to the arterial Y-graft anastomosis of the transplant pancreas. Endovascular stent placement was used to exclude the pseudoaneurysm prior to transplant pancreatectomy. During pancreatectomy, the lateral wall of the common iliac artery was found to be necrotic with significant exposure of the endovascular stent. After ligation and excision of the common iliac artery, a femorofemoral bypass was performed to revascularize the lower extremity. This case report highlights the advantage of a staged endovascular and surgical management strategy for complex mycotic pseudoaneurysms after pancreas transplant.

Purpose of Review: This review will highlight how gene editing technology using clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9) has revolutionized the xenotransplantation field, leading to the first pig-to-human kidney and heart xenotransplants. Recent Findings: CRISPR/Cas9 gene editing technology has significantly accelerated the development of multi-gene modified pigs to address the major immunological and physiological incompatibilities between pigs and humans. These gene edits include the knockout (KO) of the three porcine-specific glycan epitopes responsible for hyperacute rejection and human transgene expression targeting the coagulation and complement pathways. CRISPR/Cas9 genetic editing has also addressed a critical concern for the potential for cross-species transmission of porcine endogenous retroviruses (PERVs) by allowing the successful generation of pigs with genomically inactivated PERVs to eliminate the risk of viral transmission. Summary: CRISPR/Cas9 multi-gene edited pigs are likely to be used in the first human clinical xenotransplant trials. While genetic modifications will help protect pig xenografts from innate immune responses, genetic engineering alone will not be sufficient to prevent chronic rejection, given the overwhelming number of possible xenoantigens that can trigger adaptive immune responses and antibody-mediated rejection. Additional immunomodulatory strategies, such as targeted immunosuppression or tolerance induction, will be required for long-term survival of porcine xenografts.