Allorecognition Unveiled: Integrating Recent Breakthroughs Into the Current Paradigm.

In transplantation, genetic differences between donor and recipient trigger immune responses that cause graft rejection. Allorecognition, the process by which the immune system discriminates allogeneic grafts, targets major histocompatibility complex (MHC) and minor histocompatibility antigens. Historically, it was believed that allorecognition was solely mediated by the recipient's adaptive immune system recognizing donor-specific alloantigens.

Donor Time to Death and Kidney Transplant Outcomes in the Setting of a 3-Hour Minimum Wait Policy.

Importance: Lengthening waiting lists for organ transplant mandates the development of strategies to expand the deceased donor pool. Due to concerns regarding organ viability, most organ donation organizations internationally wait no longer than 1 to 2 hours for potential donation after circulatory death (DCD), possibly underutilizing an important organ source; UK policy mandates a minimum 3-hour wait time.

Objective: To assess whether time to death (TTD) from withdrawal of life-sustaining treatment (WLST) is associated with kidney transplant outcomes.

Quantifying measurement uncertainty in renal transplant biopsy assessment.

Introduction: Renal transplant biopsies provide insights into graft health and support decision making. The current evidence on links between biopsy scores and transplant outcomes suggests there may be numerous factors affecting biopsy scores. Here we adopt measurement science approach to investigate the sources of uncertainty in biopsy assessment and suggest techniques to improve its robustness.

Doppler ultrasound surveillance of recently formed haemodialysis arteriovenous fistula: the SONAR observational cohort study.

Background: Arteriovenous fistulas are considered the best option for haemodialysis provision, but as many as 30% fail to mature or suffer early failure.

Objective: To assess the feasibility of performing a randomised controlled trial that examines whether, by informing early and effective salvage intervention of fistulas that would otherwise fail, Doppler ultrasound surveillance of developing arteriovenous fistulas improves longer-term arteriovenous fistula patency.

Design: A prospective multicentre observational cohort study (the 'SONAR' study).

Early Ultrasound Surveillance of Newly-Created Hemodialysis Arteriovenous Fistula.

Introduction: We assess if ultrasound surveillance of newly-created arteriovenous fistulas (AVFs) can predict nonmaturation sufficiently reliably to justify randomized controlled trial (RCT) evaluation of ultrasound-directed salvage intervention.

Methods: Consenting adults underwent blinded fortnightly ultrasound scanning of their AVF after creation, with scan characteristics that predicted AVF nonmaturation identified by logistic regression modeling.

Results: Of 333 AVFs created, 65.

The impact of time to death in donors after circulatory death on recipient outcome in simultaneous pancreas-kidney transplantation.

The time to arrest donors after circulatory death is unpredictable and can vary. This leads to variable periods of warm ischemic damage prior to pancreas transplantation. There is little evidence supporting procurement team stand-down times based on donor time to death (TTD).

Antibody prevalence after three or more COVID-19 vaccine doses in individuals who are immunosuppressed in the UK: a cross-sectional study from MELODY.

Background: In the UK, additional COVID-19 vaccine booster doses and treatments are offered to people who are immunosuppressed to protect against severe COVID-19, but how best to choose the individuals that receive these vaccine booster doses and treatments is unclear. We investigated the association between seropositivity to SARS-CoV-2 spike protein with demographic, disease, and treatment-related characteristics after at least three COVID-19 vaccines in three cohorts of people who are immunosuppressed.

Methods: In a cross-sectional study using UK national disease registries, we identified, contacted, and recruited recipients of solid organ transplants, participants with rare autoimmune rheumatic diseases, and participants with lymphoid malignancies who were 18 years or older, resident in the UK, and who had received at least three doses of a COVID-19 vaccine.

Artificial Intelligence You Can Trust: What Matters Beyond Performance When Applying Artificial Intelligence to Renal Histopathology?

Although still in its infancy, artificial intelligence (AI) analysis of kidney biopsy images is anticipated to become an integral aspect of renal histopathology. As these systems are developed, the focus will understandably be on developing ever more accurate models, but successful translation to the clinic will also depend upon other characteristics of the system.In the extreme, deployment of highly performant but "black box" AI is fraught with risk, and high-profile errors could damage future trust in the technology.

Passenger donor lymphocytes: To affinity and beyond.

Graft-versus-host recognition by passenger donor lymphocytes within organ transplants can trigger host alloantibody production (Charmetant .)

Kidney Transplantation From Deceased Donors With Vaccine-induced Immune Thrombocytopenia and Thrombosis: An Updated Analysis of the UK Experience.

Background: The emergence and attendant mortality of vaccine-induced immune thrombocytopenia and thrombosis (VITT) as a consequence of vaccination against severe acute respiratory syndrome coronavirus 2 have resulted in some patients with VITT being considered as deceased organ donors. Outcomes after kidney transplantation in this context are poorly described. Because the disease seems to be mediated by antiplatelet factor 4 antibodies, there is a theoretical risk of transmission via passenger leukocytes within the allograft.

Two subsets of human marginal zone B cells resolved by global analysis of lymphoid tissues and blood.

B cells generate antibodies that are essential for immune protection, but their subgroups are poorly defined. Here, we perform undirected deep profiling of B cells in matched human lymphoid tissues from deceased transplant organ donors and blood. In addition to identifying unanticipated features of tissue-based B cell differentiation, we resolve two subsets of marginal zone B (MZB) cells differing in cell surface and transcriptomic profiles, clonal relationships to other subsets, enrichment of genes in the NOTCH pathway, distribution bias within splenic marginal zone microenvironment, and immunoglobulin repertoire diversity and hypermutation frequency.

Real-world Effectiveness of the Pfizer-BioNTech BNT162b2 and Oxford-AstraZeneca ChAdOx1-S Vaccines Against SARS-CoV-2 in Solid Organ and Islet Transplant Recipients.

Background: The clinical effectiveness of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in immunosuppressed solid organ and islet transplant (SOT) recipients is unclear.

Methods: We linked 4 national registries to retrospectively identify laboratory-confirmed SARS-CoV-2 infections and deaths within 28 d in England between September 1, 2020, and August 31, 2021, comparing unvaccinated adult SOT recipients and those who had received 2 doses of ChAdOx1-S or BNT162b2 vaccine. Infection incidence rate ratios were adjusted for recipient demographics and calendar month using a negative binomial regression model, with 95% confidence intervals.

Utilization and Outcomes of Single and Dual Kidney Transplants from Older Deceased Donors in the United Kingdom.

Background And Objectives: Kidneys from elderly deceased donors are often discarded after procurement if the expected outcomes from single kidney transplantation are considered unacceptable. An alternative is to consider them for dual kidney transplantation. We aimed to examine the utilization of kidneys from donors aged ≥60 years in the United Kingdom and compare clinical outcomes of dual versus single kidney transplant recipients.

Humoral autoimmunity after solid organ transplantation: Germinal ideas may not be natural.

Non-HLA antibody responses following solid organ transplantation have become increasingly emphasised, with several large clinical series suggesting that such responses contribute to late graft failure. Many of the responses described recognise both recipient and donor moieties of the target antigen and thus represent auto-, rather than allo-immunity. Within this rapidly evolving field, many questions remain unanswered: what triggers the response; how innate and adaptive humoral autoimmunity integrate; and most pressingly, how autoimmunity contributes to graft damage and its relationship to other effector mechanisms of graft rejection.

Kidney transplantation following uncontrolled donation after circulatory death.

Purpose Of Review: The identification and utilization of kidneys from uncontrolled donation after circulatory death (uDCD) donors for transplantation may increase transplantation rates markedly. This article summarizes the latest international results from successful uDCD kidney transplant programmes and considers how such programmes may impact on the transplant waiting list.

Recent Findings: The results of more than 1000 uDCD donor kidney transplants have been reported since 2007 from France and Spain.

A Systematic Review of Opt-out Versus Opt-in Consent on Deceased Organ Donation and Transplantation (2006-2016).

Background: Significant numbers of patients in the USA and UK die while waiting for solid organ transplant. Only 1-2% of deaths are eligible as donors with a fraction of the deceased donating organs. The form of consent to donation may affect the organs available.

Relative Frequencies of Alloantigen-Specific Helper CD4 T Cells and B Cells Determine Mode of Antibody-Mediated Allograft Rejection.

Humoral alloimmunity is now recognized as a major determinant of transplant outcome. MHC glycoprotein is considered a typical T-dependent antigen, but the nature of the T cell alloresponse that underpins alloantibody generation remains poorly understood. Here, we examine how the relative frequencies of alloantigen-specific B cells and helper CD4 T cells influence the humoral alloimmune response and how this relates to antibody-mediated rejection (AMR).

Germinal Center Alloantibody Responses Mediate Progression of Chronic Allograft Injury.

Different profiles of alloantibody responses are observed in the clinic, with those that persist, often despite targeted treatment, associated with poorer long-term transplant outcomes. Although such responses would suggest an underlying germinal center (GC) response, the relationship to cellular events within the allospecific B cell population is unclear. Here we examine the contribution of germinal center (GC) humoral alloimmunity to chronic antibody mediated rejection (AMR).

Data regarding transplant induced germinal center humoral autoimmunity.

This data is related to the research article entitled "Germinal center humoral autoimmunity independently mediates progression of allograft vasculopathy" (Harper et al., 2016) [2]. The data presented here focuses on the humoral autoimmune response triggered by transferred allogeneic CD4 T cells and includes details on: (a) the recipient splenic germinal center (GC) response; (b) augmentation of humoral autoimmunity and accelerated heart allograft rejection following transplantation from donors primed against recipient; (c) flow cytometric analysis of donor and recipient CD4 T cells for signature markers of T follicular helper cell differentiation; (d) donor endothelial cell migration in response to column purified autoantibody from recipient sera; (e) analysis of development of humoral responses in recipients following adoptive transfer of donor CD4 T cells and; (f) the development of humoral autoimmunity in mixed haematopoietic chimeric mice.

Uncontrolled DCD donation-tilting at windmills or pushing against an open door?

Wider use of donation after circulatory death donors may increase transplant numbers substantially. Most countries that have adopted donation after circulatory death donation have focused on controlled donation after circulatory death donors, whereby life-supporting treatment is withdrawn in a coordinated manner. In this issue, del Río and colleagues report the Spanish experience for kidneys transplanted from uncontrolled donation after circulatory death donors (typically individuals with sudden cardiorespiratory arrest in the community).

PreImplantation Trial of Histopathology In renal Allografts (PITHIA): a stepped-wedge cluster randomised controlled trial protocol.

Introduction: Most potential kidney transplant donors in the UK are aged over 60 years, yet increasing donor age is associated with poorer graft survival and function. Urgent preimplantation kidney biopsy can identify chronic injury, and may aid selection of better 'quality' kidneys from this group. However, the impact of biopsy on transplant numbers remains unproven.