Differences in excess mortality by recipient sex after heart transplant: An individual patient data meta-analysis.

BACKGROUND: Identification of differences in mortality risk between female and male heart transplant recipients may prompt sex-specific management strategies. Because worldwide, males of all ages have higher absolute mortality rates than females, we aimed to compare the excess risk of mortality (risk above the general population) in female vs male heart transplant recipients. METHODS: We used relative survival models conducted separately in SRTR and CTS cohorts from 1988-2019, and subsequently combined using 2-stage individual patient data meta-analysis, to compare the excess risk of mortality in female vs male first heart transplant recipients, accounting for the modifying effects of donor sex and recipient current age. RESULTS: We analyzed 108,918 patients. When the donor was male, female recipients 0-12 years (Relative excess risk (RER) 1.13, 95% CI 1.00-1.26), 13-44 years (RER 1.17, 95% CI 1.10-1.25), and ≥45 years (RER 1.14, 95% CI 1.02-1.27) showed higher excess mortality risks than male recipients of the same age. When the donor was female, only female recipients 13-44 years showed higher excess risks of mortality than males (RER 1.09, 95% CI 1.00-1.20), though not significantly (p = 0.05). CONCLUSIONS: In the setting of a male donor, female recipients of all ages had significantly higher excess mortality than males. When the donor was female, female recipients of reproductive age had higher excess risks of mortality than male recipients of the same age, though this was not statistically significant. Further investigation is required to determine the reasons underlying these differences.

Policies and practice of solid organ donation amongst people living with HIV in Canada: time for education and re-evaluation.

The numbers of organ donors in Canada and the USA fall short of increasing demand, resulting in increased morbidity, poor health outcomes, higher medical costs and death of many individuals waitlisted for transplantation. In the US, since 2013 when the US HIV Organ Policy Equity (HOPE) Act lifted the ban on organ donation between people living with HIV, the option of using organs from People with HIV became a reality. In Canada, HIV diagnosis was an exclusion criterion to organ donation until 2017, when permission was granted if requirements for 'exceptional distribution' could be met. Still, donation of organs from people with HIV poses challenges. Herein, we overview policies involving donors with HIV in Canada in order to inform healthcare providers, researchers and the community. We also advocate for the need to reassess these policies, highlight educational needs and engage interest in advancing research to inform policy reforms.

Immunosuppression and cancer risk in kidney transplant recipients: A retrospective cohort study.

We assessed whether contemporary immunosuppression agents were associated with cancer among kidney transplant recipients (KTR), and if this association varied by age and sex. We studied a retrospective province-wide cohort of primary KTR (1997-2016). Employing multivariable Cox models, we estimated associations of cumulative doses of prednisone, mycophenolate and tacrolimus administered over the past 10 years, lagged by 2 years, with the incidence of primary malignant neoplasms (PMN). We assessed interactions with age and sex. To assess the impact of exposure recency, we used weighted cumulative exposure (WCE) modeling. Among 1064 KTR, 108 (10.2%) developed PMN over median follow-up of 73 months (interquartile range: 32-120). Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of 0.96 (0.64-1.43), 1.34 (0.96-1.86), and 1.06 (0.88-1.29) were estimated for cumulative daily doses of prednisone (5 mg), mycophenolate (1000 mg), and tacrolimus (2 mg) administered continuously over the past 10 years, respectively. PMN risk associated with cumulative tacrolimus exposure was modified by age (interaction p = .035) and was more pronounced in 15-year and 30-year-old KTR (aHRs of 1.57 [1.08-2.28] and 1.31 [1.03-1.66], respectively) in comparison to older KTR. PMN risk increase associated with higher cumulative mycophenolate dose was more pronounced in females (aHR = 1.86 [1.15-3.00]) than in males (aHR = 1.16 [0.74-1.81]; interaction p = .131). WCE analyses suggested increased PMN risk the higher the mycophenolate doses taken 5-10 years ago. A trend toward increased PMN risk with long-term mycophenolate exposure, particularly in females, and more pronounced risk with long-term tacrolimus exposure in younger KTR, identify opportunities for tailored immunosuppression to mitigate cancer risk.

KEeP ACTIVe Club Study: Kidney Transplant Recipients' Experiences of a Physical Activity and Social Interaction Virtual Group.

Background: It can be difficult for kidney transplant recipients (KTRs) to be physically active after their transplantation. Physical inactivity is a risk factor for cardiovascular disease, one of the leading cause of death among KTRs. To help KTRs start and maintain a physical activity routine, we developed the KEeP ACTIVe Club, a 6-month online intervention with access to a kinesiologist, a patient partner, and a private support group with an online platform (Facebook). Objective: The objective of this study was to capture the participants' experiences of the KEeP ACTIVe Club. Design: Individual interviews. Setting: The Center hospitalier de l'Université de Montréal (CHUM) and the McGill University Health Center (MUHC) kidney transplant programs. Participants: Kidney transplant recipients who participated in the KEeP ACTIVe Club. Methods: Between October and December 2021, we conducted 11 individual semi-directed interviews with KTRs from 2 urban kidney transplant programs who participated in the KEeP ACTIVe Club. The interviews were digitally recorded and transcribed. Thematic analysis was conducted. Results: Participants' principal motivation to participate in the KEeP ACTIVe Club was to improve their physical fitness following their transplant in a pandemic period. One of the main benefits of the KEeP ACTIVe Club was the improvement of participant's self-confidence and the knowledge gained regarding exercises adapted to their reality as KTRs. However, the small number of participants and the schedules of classes offered were viewed as a pitfall of the current intervention. Finally, the peer mentoring and support gained by other participants were important and viewed as highly impactful aspects of the KEeP ACTIVe Club. Limitations: Only 11 of the 18 patients who participated in the KEeP ACTIVe Club took part in the interviews. Conclusion: Participants reported a positive experience with the KEeP ACTIVe Club. Peer mentoring and support gained from other participants seem to be essential aspects of the experience within the KEeP ACTIVe Club. This program is a good avenue to offer in post-transplant care to help KTRs to be more active and to connect with other patients.

Contexte: Il peut être difficile pour les receveurs d'une greffe de rein d'être actifs physiquement après la transplantation. L'inactivité est un facteur de risque de maladie cardiovasculaire, une des principales causes de décès chez les greffés du rein. Afin d'aider ces patients à entreprendre une routine d'activité physique et à la maintenir, nous avons développé le KEeP ACTIVe Club, une intervention en ligne d'une durée de six mois qui donne accès à un kinésiologue, à un patient partenaire et à un groupe privé de soutien par le biais d'une plateforme en ligne (Facebook). Objectifs: Connaître l'expérience des participants au KEeP ACTIVe Club. Conception: Entretiens individuels. Cadre: Les programme de transplantation rénale du Center hospitalier de l'Université de Montréal (CHUM) et du Centre universitaire de santé McGill (CUSM). Participants: Des receveurs d'une greffe de rein ayant participé au KEeP ACTIVe Club. Méthodologie: Entre octobre et décembre 2021, nous avons mené 11 entretiens individuels semi-dirigés avec des receveurs d'une greffe rénale qui ont participé au KEeP ACTIVe Club dans deux programmes de transplantation en center urbain. Les entretiens ont été enregistrés en mode numérique, transcrits, puis une analyze thématique a été réalisée. Résultats: La principale motivation des receveurs à participer au KEeP ACTIVe Club était d'améliorer leur condition physique après la greffe, en période pandémique. Les principaux avantages d'avoir participé au KEeP ACTIVe Club ont été l'augmentation de la confiance en soi et l'acquisition de connaissances sur des exercices adaptés à leur réalité de greffés du rein. Le faible nombre de participants et l'horaire des cours proposés ont été perçus comme des faiblesses de l'intervention. Enfin, le mentorat par les pairs et le soutien reçu des autres participants ont été jugés importants et perçus comme des aspects très positifs du KEeP ACTIVe Club. Limites: Sur les dix-huit patients inscrits au KEeP ACTIVe Club, seuls onze ont participé aux entrevues. Conclusion: Les participants ont déclaré avoir eu une expérience positive avec le KEeP ACTIVe Club. Le mentorat par les pairs et le soutien reçu des autres participants semblent être des aspects essentiels de l'expérience positive vécue au sein du KEeP ACTIVe Club. Ce programme est une bonne avenue à proposer dans les soins post-transplantation pour aider les greffés du rein à être plus actifs physiquement et à échanger avec d'autres patients.

Communicating About Precision Transplantation Tools.

Purpose of review: Precision tools that ensure molecular compatibility can help prevent rejection and improve kidney transplantation outcomes. However, these tools will generate controversy because they are perceived to and can in fact impact equity in the ethics of allocation. They may also affect the extent to which physicians can advocate for their patient fiduciaries, as generally required by Canadian professional ethics and law. Sources of information: Electronic databases such as Google Scholar and PubMed were searched for peer-reviewed literature, and Google search engine was used to identify the news articles, jurisprudence, legal information, and other relevant websites cited. Methods: We discuss controversies precision transplantation tools will likely generate, consider what challenges will arise from their implementation, and provide recommendations of avenues and content for communication to address these issues. Key findings: Communication about the translation of new precision tools will be challenging as media portrayals of transplantation often focus on individual narratives about access to transplantation and fail to center the issues of utility, allocation, and rejection. Incomplete portrayals of this nature will need to be countered with explanations of how new precision tools can be of net benefit when implemented equitably, as maintaining trust in the donation and transplantation system is key. Limitations: Our manuscript focuses on precision medicine applications pertaining to the implementation of molecular compatibility in transplantation. Distinct communication content and avenues may need to be considered in other contexts. Implications: Clear, accurate, and strategic communication is key to managing translation of precision medicine tools. For this purpose, we provide detailed recommendations for stakeholder engagement, content, and avenues for communicating about precision transplantation tools.

Motif de la revue: Les outils de précision assurant la compatibilité moléculaire peuvent aider à prévenir le rejet et à améliorer les résultats de la transplantation rénale. Or, ces outils susciteront une controverse parce qu'ils sont perçus comme ayant une incidence sur l'équité dans l'éthique de l'allocation, et qu'ils peuvent effectivement en avoir une. Ces outils sont également susceptibles d'influer sur les limites au sein desquelles les médecins peuvent défendre les intérêts de leurs patients fiduciaires, comme l'exigent l'éthique professionnelle et le droit canadien. Sources: Des bases de données électroniques telles que Google Scholar et PubMed ont été consultées à la recherche de la documentation évaluée par des pairs. Le moteur de recherche Google a servi à répertorier les articles de presse, la jurisprudence, les informations juridiques et les autres sites Web pertinents cités. Méthodologie: Nous discutons des controverses qui seront vraisemblablement générées par les nouveaux outils de précision liés à la transplantation. Nous examinons également les défis qui découleront de leur mise en œuvre et nous formulons des recommandations sur les stratégies et le contenu à adopter dans les communications qui aborderont ces questions. Principales observations: La communication entourant l'application des nouveaux outils de précision posera un défi, car les représentations médiatiques de la transplantation se concentrent le plus souvent sur des récits individuels liés à l'accès à la transplantation, et ne mettent pas en lumière les problèmes liés à l'utilité, l'attribution et le rejet. Ces représentations incomplètes devront être contrebalancées par des explications sur la façon dont les nouveaux outils de précision pourront être bénéfiques s'ils sont mis en œuvre équitablement; car il est essentiel de maintenir la confiance dans le système de don et de transplantation. Limites: Notre article porte sur les applications de la médecine de précision en lien avec la mise en œuvre d'outils mesurant la compatibilité moléculaire en transplantation. Il faudra possiblement envisager des stratégies et un contenu de communication distincts dans d'autres contextes. Conclusion: Une stratégie de communication claire et précise est essentielle pour gérer l'application des outils de la médecine de précision. À cette fin, nous fournissons des recommandations détaillées sur l'engagement des intervenants, ainsi qu'en matière de contenu et de stratégies pour les communications liées aux nouveaux outils de précision en transplantation.

A Multinational Cohort Study Examining Sex Differences in Excess Risk of Death With Graft Function After Kidney Transplant.

BACKGROUND: Kidney transplant recipients show sex differences in excess overall mortality risk that vary by donor sex and recipient age. However, whether the excess risk of death with graft function (DWGF) differs by recipient sex is unknown. METHODS: In this study, we combined data from 3 of the largest transplant registries worldwide (Scientific Registry of Transplant Recipient, Australia and New Zealand Dialysis and Transplant Registry, and Collaborative Transplant Study) using individual patient data meta-analysis to compare the excess risk of DWGF between male and female recipients of a first deceased donor kidney transplant (1988-2019), conditional on donor sex and recipient age. RESULTS: Among 463 895 individuals examined, when the donor was male, female recipients aged 0 to 12 y experienced a higher excess risk of DWGF than male recipients (relative excess risk 1.68; 95% confidence interval, 1.24-2.29); there were no significant differences in other age intervals or at any age when the donor was female. There was no statistically significant between-cohort heterogeneity. CONCLUSIONS: Given the lack of sex differences in the excess risk of DWGF (other than in prepubertal recipients of a male donor kidney) and the known greater excess overall mortality risk for female recipients compared with male recipients in the setting of a male donor, future study is required to characterize potential sex-specific causes of death after graft loss.

The Banff 2022 Kidney Meeting Report: Reappraisal of microvascular inflammation and the role of biopsy-based transcript diagnostics.

The XVI-th Banff Meeting for Allograft Pathology was held at Banff, Alberta, Canada, from 19th to 23rd September 2022, as a joint meeting with the Canadian Society of Transplantation. To mark the 30th anniversary of the first Banff Classification, premeeting discussions were held on the past, present, and future of the Banff Classification. This report is a summary of the meeting highlights that were most important in terms of their effect on the Classification, including discussions around microvascular inflammation and biopsy-based transcript analysis for diagnosis. In a postmeeting survey, agreement was reached on the delineation of the following phenotypes: (1) "Probable antibody-mediated rejection (AMR)," which represents donor-specific antibodies (DSA)-positive cases with some histologic features of AMR but below current thresholds for a definitive AMR diagnosis; and (2) "Microvascular inflammation, DSA-negative and C4d-negative," a phenotype of unclear cause requiring further study, which represents cases with microvascular inflammation not explained by DSA. Although biopsy-based transcript diagnostics are considered promising and remain an integral part of the Banff Classification (limited to diagnosis of AMR), further work needs to be done to agree on the exact classifiers, thresholds, and clinical context of use.

The Banff 2022 Kidney Meeting Work Plan: Data-driven refinement of the Banff Classification for renal allografts.

The XVIth Banff Meeting for Allograft Pathology was held in Banff, Alberta, Canada, from September 19 to 23, 2022, as a joint meeting with the Canadian Society of Transplantation. In addition to a key focus on the impact of microvascular inflammation and biopsy-based transcript analysis on the Banff Classification, further sessions were devoted to other aspects of kidney transplant pathology, in particular T cell-mediated rejection, activity and chronicity indices, digital pathology, xenotransplantation, clinical trials, and surrogate endpoints. Although the output of these sessions has not led to any changes in the classification, the key role of Banff Working Groups in phrasing unanswered questions, and coordinating and disseminating results of investigations addressing these unanswered questions was emphasized. This paper summarizes the key Banff Meeting 2022 sessions not covered in the Banff Kidney Meeting 2022 Report paper and also provides an update on other Banff Working Group activities relevant to kidney allografts.

Canadian Kidney Transplant Professionals' Perspectives on Precision Medicine and Molecular Matching in Kidney Allocation.

Background: Antibody-mediated rejection is an important cause of kidney transplant loss. A new strategy requiring application of precision medicine tools in transplantation considers molecular compatibility between donors and recipients and holds the promise of improved immunologic risk, preventing rejection and premature graft loss. The objective of this study was to gather Canadian transplant professionals' perspectives on molecular compatibility in kidney transplantation. Methods: Seventeen Canadian transplant professionals (14 nephrologists, 2 nurses, and 1 surgeon) participated in semistructured interviews in 2021. The interviews were digitally recorded, transcribed, and analyzed using the qualitative description approach. Results: Participants identified fair access to transplantation as the most important principle in kidney allocation. Molecular compatibility was viewed as a promising innovation. However, participants were concerned about increased waiting times, negative impact on some patients, and potential problems related to the adequacy of information explaining this new technology. To mitigate the challenges associated with molecular matching, participants suggested integrating a maximum waiting time for molecular-matched kidneys and expanding the program nationally/internationally. Conclusions: Molecular matching in kidney transplantation is viewed as a promising technology for decreasing the incidence of antibody-mediated rejection and improving graft survival. Further studies are needed to determine how to ethically integrate this technology into the kidney allocation algorithm.

NephroCAGE-German-Canadian Consortium on AI for Improved Kidney Transplantation Outcome: Protocol for an Algorithm Development and Validation Study.

BACKGROUND: Recent advances in hardware and software enabled the use of artificial intelligence (AI) algorithms for analysis of complex data in a wide range of daily-life use cases. We aim to explore the benefits of applying AI to a specific use case in transplant nephrology: risk prediction for severe posttransplant events. For the first time, we combine multinational real-world transplant data, which require specific legal and technical protection measures. OBJECTIVE: The German-Canadian NephroCAGE consortium aims to develop and evaluate specific processes, software tools, and methods to (1) combine transplant data of more than 8000 cases over the past decades from leading transplant centers in Germany and Canada, (2) implement specific measures to protect sensitive transplant data, and (3) use multinational data as a foundation for developing high-quality prognostic AI models. METHODS: To protect sensitive transplant data addressing the first and second objectives, we aim to implement a decentralized NephroCAGE federated learning infrastructure upon a private blockchain. Our NephroCAGE federated learning infrastructure enables a switch of paradigms: instead of pooling sensitive data into a central database for analysis, it enables the transfer of clinical prediction models (CPMs) to clinical sites for local data analyses. Thus, sensitive transplant data reside protected in their original sites while the comparable small algorithms are exchanged instead. For our third objective, we will compare the performance of selected AI algorithms, for example, random forest and extreme gradient boosting, as foundation for CPMs to predict severe short- and long-term posttransplant risks, for example, graft failure or mortality. The CPMs will be trained on donor and recipient data from retrospective cohorts of kidney transplant patients. RESULTS: We have received initial funding for NephroCAGE in February 2021. All clinical partners have applied for and received ethics approval as of 2022. The process of exploration of clinical transplant database for variable extraction has started at all the centers in 2022. In total, 8120 patient records have been retrieved as of August 2023. The development and validation of CPMs is ongoing as of 2023. CONCLUSIONS: For the first time, we will (1) combine kidney transplant data from nephrology centers in Germany and Canada, (2) implement federated learning as a foundation to use such real-world transplant data as a basis for the training of CPMs in a privacy-preserving way, and (3) develop a learning software system to investigate population specifics, for example, to understand population heterogeneity, treatment specificities, and individual impact on selected posttransplant outcomes. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/48892.

Updates in Kidney Transplantation From the 2022 Banff-Canadian Society of Transplantation Joint Meeting: Conference Report.

Purpose of the Conference: The 2022 Banff-Canadian Society of Transplantation Meeting in Banff, Alberta, brought together transplant professionals to review new developments across various aspects of solid organ transplantation (SOT) in Canada. Sources of Information: Presentations included consensus recommendations from expert-led forums; experiences with new procedures and legislation; reports from public health data repositories; original clinical and laboratory research; and industry updates regarding novel technologies. Speakers referenced articles and reports published in peer-reviewed journals and online, and unpublished data and preliminary findings. Methods: All authors attended presentations in-person or virtually. Recordings of select presentations were available for later review. Summaries emphasize concepts indicated by speakers as new and clinically relevant. Key Findings: The COVID-19 pandemic disproportionately affected solid organ transplant recipients (SOTRs), who experience worse outcomes of COVID-19 infection than the general population. Vaccinations demonstrate an attenuated immunological response in SOTRs yet provide meaningful protection. Monoclonal antibodies are effective for both passive immunization and treatment of COVID-19 in SOTRs. Infection control protocols have driven the development of virtual methods for clinical research, such as using home blood draws and virtual follow-up to evaluate vaccine efficacy in SOTRs; and patient care delivery, such as employing telerehabilitation post transplant. Access to living kidney donation is limited by various disincentives experienced by potential donors, which may be overcome by more efficient evaluations including a One-Day Living Kidney Donor Assessment Clinic. The International Donation and Transplantation Legislative and Policy Forum provided a means of establishing consensus guidance for organ donation and transplantation (ODT) program policy to standardize delivery across jurisdictions. The implementation of a deemed consent model for organ and tissue donation in Nova Scotia may provide insight as to whether this model indeed improves access to organs. Canada's Indigenous population experiences unique barriers to transplantation, prompting efforts for more inclusive ODT policy-making. The Pan-Canadian ODT Data and Performance Reporting System Project has defined performance quality indicators, of which iTransplant and other point-of-care software solutions may facilitate collection; however, these endeavors ultimately require information technology infrastructure that exceeds the capabilities of the existing Canadian Organ Replacement Register and Canadian Transplant Registry. Pig-to-human xenotransplantation requires genetic modification of pigs and xenoantibody testing in recipients but may yet prove viable. Serum cell-free DNA, urine biomarkers, and genetic markers offer an alternative to routine biopsy for identifying subclinical rejection. Modified perfusion temperatures and perfusion solutions with hydrogen sulfide donor compounds may improve organ preservation. Molecular compatibility tools provide another means of improving SOTR outcomes, and the Genome Canada Transplant Consortium has been examining important considerations of their implementation. Limitations: We were unable to capture all presentations and topics at the meeting due to the sizable quantity and variety. Topics ultimately excluded from this summary include those in pathology including Banff Classification updates; those unique to extra-renal SOT; as well as numerous abstract and poster presentations, allied health provider forums, and business meetings. A portion of the material was presented by speakers prior to peer-review or publication. Implications: The various conference presentations summarized in this report identify methods by which individual clinicians and provincial ODT programs may improve access, delivery, and quality of SOT care in Canada, while additionally identifying gaps in the literature that investigators are encouraged to pursue.

Objectifs de la conférence: En 2022, le congrès annuel de la Société canadienne de transplantation qui s'est tenu à Banff (Alberta) a réuni des professionnels de la transplantation qui se sont penchés sur les nouveaux développements dans divers aspects de la transplantation d'organes solides (TOS) au Canada. Sources: Les présentations portaient notamment sur : les recommandations consensuelles issues de forums dirigés par des experts; l'expérience avec les nouvelles procédures et lois; des rapports provenant de dépôts de données de santé publique; des recherches cliniques et des recherches de laboratoire originales; et les mises à jour du secteur sur les nouvelles technologies. Les intervenants ont fait référence à des articles et rapports publiés en ligne et dans des revues évaluées par les pairs, ainsi qu'à des données non publiées et des conclusions préliminaires. Méthodologie: Tous les auteurs ont assisté aux présentations en personne ou virtuellement. Les enregistrements de certaines présentations étaient disponibles pour visionnement ultérieur. Les résumés mettent l'accent sur les concepts jugés comme nouveaux et cliniquement pertinents par les intervenants. Principaux résultats: La pandémie de COVID-19 a affecté les receveurs d'une transplantation d'organe solide (RTOS) de manière disproportionnée; ces derniers ayant suivi une évolution plus défavorable que la population générale à la suite d'une infection à la COVID-19. La vaccination, bien qu'elle offre une protection significative, montre une réponse immunologique plus faible chez les RTOS. Les anticorps monoclonaux sont efficaces à la fois pour l'immunization passive et le traitement de la COVID-19 chez les RTOS. Les protocoles de contrôle des infections ont mené au développement de méthodes virtuelles pour la recherche clinique (p. ex. prélèvements sanguins à domicile, suivi virtuel pour évaluer l'efficacité du vaccin chez les RTOS) et la prestation de soins aux patients (p. ex. rééducation à distance) après la transplantation. L'accès au don de rein vivant est limité par divers facteurs dissuasifs pour les donneurs potentiels, mais ces obstacles peuvent être surmontés par des évaluations plus efficaces, notamment par une clinique d'un jour pour évaluer la candidature des donneurs vivants de rein. Le Forum législatif et politique international sur le don et la transplantation a fourni un moyen d'établir des lignes directrices consensuelles pour la politique du program de dons d'organes et de transplantation (DOT), dans l'objectif de normaliser la prestation d'une juridiction à l'autre. La mise en œuvre en Nouvelle-Écosse du consentement présumé pour le don d'organes et de tissus pourrait aider à déterminer si un tel modèle améliore effectivement l'accès aux organes. Les populations autochtones du Canada sont confrontées à des obstacles uniques en matière de transplantation, ce qui encourage les efforts visant l'élaboration de politiques plus inclusives en matière de DOT. Le Projet de système pancanadien de données et de mesure de la performance pour les DOT a défini des indicateurs de performance, dont iTransplant et d'autres solutions logicielles pour les points de soins, qui peuvent faciliter la collecte des données; ces derniers nécessitent toutefois une infrastructure informatique qui dépasse les capacités du Registre canadien des insuffisances et des transplantations d'organes et du Registre canadien de transplantation. La xénogreffe de porc à humain requiert une modification génétique des porcs et le dépistage de xénoanticorps chez les receveurs, mais elle peut encore s'avérer viable. L'ADN acellulaire sérique, les biomarqueurs urinaires et les marqueurs génétiques offrent une alternative à la biopsie de routine pour identifier les rejets subcliniques. Des températures de perfusion modifiées et des solutions de perfusion contenant des composés générateurs de sulfure d'hydrogène peuvent améliorer la conservation des organes. Les outils de compatibilité moléculaire offrent un autre moyen d'améliorer les résultats des RTOS, et le Genome Canada Transplant Consortium a examiné les aspects importants à prendre en considération pour leur mise en œuvre. Limites: Nous n'avons pas été en mesure d'assister à toutes les présentations en raison du grand nombre et de la grande diversité des sujets abordés. Les sujets exclus de ce résumé incluent la pathologie, notamment les mises à jour de la classification Banff; les sujets propres à la TOS extrarénale; ainsi que de nombreux résumés et présentations d'affiches, forums de prestataires de soins de santé alliés et réunions d'affaires. Une partie du matériel présenté l'a été avant l'examen par les pairs ou la publication. Conclusion: Les présentations du congrès qui sont résumées dans le présent rapport identifient les méthodes que les programs provinciaux de DOT et les cliniciens pourraient employer pour améliorer l'accès, la prestation et la qualité des soins en TOS au Canada, et soulignent des lacunes dans la littérature que les chercheurs sont encouragés à creuser.

Influence of donor sex and age on graft outcome in kidney transplantation.

BACKGROUND AND HYPOTHESIS: There is a known recipient sex-dependent association between donor sex and kidney transplant survival. We hypothesized that donor age also modifies the association between donor sex and graft survival. METHODS: First deceased donor kidney transplant recipients (1988-2019, n = 461 364) recorded in the Scientific Registry of Transplant Recipients, Australia and New Zealand Dialysis and Transplant Registry, and the Collaborative Transplant Study were analyzed. We used multivariable Cox regression models to estimate the association between donor sex and death censored graft loss, accounting for the modifying effects of recipient sex and donor age; donor age was categorized as 5-19, 20-34, 35-49, 50-59, and ≥ 60 years. Results from cohort-specific Cox models were combined using individual patient data meta-analysis. RESULTS: Among female recipients of donors aged < 60 years, graft loss hazards did not differ by donor sex; recipients of female donors ≥ 60 years showed significantly lower graft loss hazards than recipients of male donors of the same age (combined adjusted hazard ratio, aHR 0.90, 95% CI 0.86-0.94). Among male recipients, female donors aged < 50 years were associated with significantly higher graft loss hazards than same-aged male donors (5-19 years: aHR 1.11, 95% CI 1.02-1.21; 20-34 years: aHR 1.08, 95% CI 1.02-1.15; 35-49 years: aHR 1.07, 95% CI 1.04-1.10). There were no significant differences in graft loss by donor sex among male recipients of donors aged ≥ 50 years. CONCLUSION: Donor age modifies the association between donor sex and graft survival. Older female donors were associated with similar or lower hazards of graft failure than older male donors in both male and female recipients, suggesting a better functional reserve of older female donor kidneys.

Storytelling for impact: the creation of a storytelling program for patient partners in research.

Storytelling is a powerful means to evoke empathy and understanding among people. When patient partners, which include patients, family members, caregivers and organ donors, share their stories with health professionals, this can prompt listeners to reflect on their practice and consider new ways of driving change in the healthcare system. However, a growing number of patient partners are asked to 'share their story' within health care and research settings without adequate support to do so. This may ultimately widen, rather than close, the gap between healthcare practitioners and people affected by chronic disease in this new era of patient and public involvement in research. To better support patient partners with storytelling in the context of a patient-oriented research network, Canadians Seeking Solutions and Innovations to Overcome Chronic Kidney Disease (Can-SOLVE CKD) Network adapted an existing in-person storytelling workshop for patient educators within a hospital setting. The result is a 6-week virtual program called Storytelling for Impact, which guides patients, family members, caregivers and organ donors in developing impactful stories and sharing them at health care and research events, e.g., conferences. The online series of synchronous workshops is co-facilitated by story coaches, who are program alumni and Can-SOLVE CKD staff with trained storytelling experience. Each story follows a structure that includes a call to action, which aims to positively impact the priority-setting and delivery of care and research in Canada. The program has been a transformational process for many who have completed it, and numerous other health organizations have expressed interest in sharing this tool with their own patient partners. As result, we have also created an asynchronous online program that can be used by other interested parties outside our network. Patient partners who share their stories can be powerful mediators for inspiring changes in the health care and research landscape, with adequate structured support. We describe two novel programs to support patient partners in impactful storytelling, which are applicable across all health research disciplines. Additional resources are required for sustainability and scale up of training, by having alumni train future storytellers.

Storytelling is a powerful means to evoke empathy and understanding among people. When patient partners share their stories with health professionals, this can prompt listeners to reflect on their practice and consider new ways of improving the healthcare system. However, as a growing number of patient partners are asked to 'share their story' within health care and research settings, there is often not enough tools and resources to support them in preparing their stories in a way that will be impactful for the audience members. Our kidney research network sought to create a novel in-person storytelling program to address this gap within our health research context. The result is a 6-week program called Storytelling for Impact, which guides patient partners­which includes patients, family members, caregivers and organ donors­in developing impactful stories and sharing them in a formal setting. The program is led by story coaches, who are patient partners and staff with trained storytelling experience. Participants are encouraged to include a call to action in their story, which aims to outline clear ways in which health professionals can facilitate positive change in health research or care. Many participants have described the program as transformational, and numerous other health organizations have expressed interest in sharing this tool with their own patient partners. As a result, we have also created a second online program that can be used by other interested parties outside our network. This paper highlights the adaptation process, content, participant feedback and next steps for the program.

A registry-based population study of the HLA in Québec, Canada.

As part of the worldwide effort to better characterize HLA diversity in populations, we have studied the population of Québec in Canada. This province has been defined by a complex history with multiple founder effects and migration patterns. We analyzed the typing data of 3806 individuals registered in Héma-Québec's Registry, which covered most administrative regions in Québec. Typing information was resolved at the second field level of resolution by next-generation sequencing (NGS) or by Sanger sequencing. We used the HLA-net.eu GENE[RATE] tools to estimate allele and two-locus haplotype frequencies for HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1, as well as Hardy-Weinberg equilibrium (HWE), selective neutrality, and linkage disequilibrium. The chord genetic distance was also calculated between administrative regions and was visualized using non-metric multidimensional scaling (NMDS) analysis. While most individual regions were in HWE, HWE was rejected for the province considered as a whole. Some regions exhibited signatures of selection, mostly toward an excess of heterozygotes. Allele and haplotype frequencies revealed outlier regions that strongly differed from the other regions. NMDS plots also showed differences between regions. The administrative regions of the province of Québec displayed heterogeneity in their HLA profiles. This heterogeneity was attributable to differing allele and haplotype specificities by region. In particular, regions 02-Saguenay-Lac-Saint-Jean and 01-Bas-St-Laurent diverged from the rest of the regions. The urban regions 06-Montréal and 13-Laval were very diversified in their HLA profiles. Together, these results will help optimize donor recruitment strategies in Québec.

Adding epitope compatibility to deceased donor kidney allocation criteria: recommendations from a pan-Canadian online public deliberation.

BACKGROUND: The widening supply-demand imbalance for kidneys necessitates finding ways to reduce rejection and improve transplant outcomes. Human leukocyte antigen (HLA) epitope compatibility between donor and recipient may minimize premature graft loss and prolong survival, but incorporating this strategy to deceased donor allocation criteria prioritizes transplant outcomes over wait times. An online public deliberation was held to identify acceptable trade-offs when implementing epitope compatibility to guide Canadian policymakers and health professionals in deciding how best to allocate kidneys fairly. METHODS: Invitations were mailed to 35,000 randomly-selected Canadian households, with over-sampling of rural/remote locations. Participants were selected for socio-demographic diversity and geographic representation. Five two-hour online sessions were held from November-December 2021. Participants received an information booklet and heard from expert speakers prior to deliberating on how to fairly implement epitope compatibility for transplant candidates and governance issues. Participants collectively generated and voted on recommendations. In the final session, kidney donation and allocation policymakers engaged with participants. Sessions were recorded and transcribed. RESULTS: Thirty-two individuals participated and generated nine recommendations. There was consensus on adding epitope compatibility to the existing deceased donor kidney allocation criteria. However, participants recommended including safeguards/flexibility around this (e.g., mitigating declining health). They called for a transition period to epitope compatibility, including an ongoing comprehensive public education program. Participants unanimously recommended regular monitoring and public sharing of epitope-based transplant outcomes. CONCLUSIONS: Participants supported adding epitope compatibility to kidney allocation criteria, but advised safeguards and flexibility around implementation. These recommendations provide guidance to policymakers about incorporating epitope-based deceased donor allocation criteria.

Public values and guiding principles for implementing epitope compatibility in kidney transplantation allocation criteria: results from a Canadian online public deliberation.

BACKGROUND: Epitope compatibility in deceased donor kidney allocation is an emerging area of precision medicine (PM), seeking to improve compatibility between donor kidneys to transplant candidates in the hope of avoiding kidney rejection. Though the potential benefits of using epitope compatibility are promising, the implied modification of deceased organ allocation criteria requires consideration of significant clinical and ethical trade-offs. As a matter of public policy, these trade-offs should consider public values and preferences. We invited members of the Canadian public to participate in a deliberation about epitope compatibility in deceased donor kidney transplantation; to identify what is important to them and to provide recommendations to policymakers. METHODS: An online public deliberation was conducted with members of the Canadian public, in which participants were asked to construct recommendations for policymakers regarding the introduction of epitope compatibility to kidney allocation criteria. In the present paper, a qualitative analysis was conducted to identify the values reflected in participants' recommendations. All virtual sessions were recorded, transcribed, and analyzed using NVivo 12 software. RESULTS: Thirty-two participants constructed nine recommendations regarding the adoption of epitope compatibility into deceased donor kidney allocation. Five values were identified that drove participants' recommendations: Health Maximization, Protection/Mitigation of Negative Impacts, Fairness, Science/Evidence-based Healthcare, and Responsibility to Maintain Trust. Conflicts between these values were discussed in terms of operational principles that were required for epitope compatibility to be implemented in an acceptable manner: the needs for Flexibility, Accountability, Transparent Communication and a Transition Plan. All nine recommendations were informed by these four principles. Participant deliberations were often dominated by the conflict between Health Maximization and Fairness or Protection/Mitigation of Negative Impacts, which was discussed as the need for Flexibility. Two additional values (Efficient Use of Resources and Logic/Rationality) were also discussed and were reasons for some participants voting against some recommendations. CONCLUSIONS: Public recommendations indicate support for using epitope compatibility in deceased donor kidney allocation. A flexible approach to organ allocation decision-making may allow for the balancing of Health Maximization against maintaining Fairness and Mitigating Negative Impacts. Flexibility is particularly important in the context of epitope compatibility and other PM initiatives where evidence is still emerging.

Clinical application of immune repertoire sequencing in solid organ transplant.

Background: Measurement of T cell receptor (TCR) or B cell receptor (BCR) gene utilization may be valuable in monitoring the dynamic changes in donor-reactive clonal populations following transplantation and enabling adjustment in therapy to avoid the consequences of excess immune suppression or to prevent rejection with contingent graft damage and to indicate the development of tolerance. Objective: We performed a review of current literature to examine research in immune repertoire sequencing in organ transplantation and to assess the feasibility of this technology for clinical application in immune monitoring. Methods: We searched MEDLINE and PubMed Central for English-language studies published between 2010 and 2021 that examined T cell/B cell repertoire dynamics upon immune activation. Manual filtering of the search results was performed based on relevancy and predefined inclusion criteria. Data were extracted based on study and methodology characteristics. Results: Our initial search yielded 1933 articles of which 37 met the inclusion criteria; 16 of these were kidney transplant studies (43%) and 21 were other or general transplantation studies (57%). The predominant method for repertoire characterization was sequencing the CDR3 region of the TCR ß chain. Repertoires of transplant recipients were found to have decreased diversity in both rejectors and non-rejectors when compared to healthy controls. Rejectors and those with opportunistic infections were more likely to have clonal expansion in T or B cell populations. Mixed lymphocyte culture followed by TCR sequencing was used in 6 studies to define an alloreactive repertoire and in specialized transplant settings to track tolerance. Conclusion: Methodological approaches to immune repertoire sequencing are becoming established and offer considerable potential as a novel clinical tool for pre- and post-transplant immune monitoring.

P32: a sex- and gender-sensitive model for evidence-based precision medicine: from knowledge generation to implementation in the field of kidney transplantation.

Precision medicine emerged as a promising approach to identify suitable interventions for individual patients with a particular health concern and at various time points. Technology can enable the acquisition of increasing volumes of clinical and "omics" data at the individual and population levels and support advanced clinical decision making. However, to keep pace with evolving societal realities and developments, it is important to systematically include sex- and gender-specific considerations in the research process, from the acquisition of knowledge to implementation. Building on the foundations of evidence-based medicine and existing precision medicine frameworks, we propose a novel evidence-based precision medicine framework in the form of the P32model, which considers individual sex-related (predictive [P1], preventive [P2], and personalized [P3] medicine) and gender-related (participatory [P4], psychosocial [P5], and percipient [P6] medicine) domains and their intersection with ethnicity, geography, and other demographic and social variables, in addition to population, community, and public dimensions (population-informed [P7], partnered with community [P8], and public-engaging [P9] medicine, respectively). Through its ability to contextualize and reflect on societal realities and developments, our model is expected to promote consideration of diversity, equity, and inclusion principles and, thus, enrich science, increase reproducibility of research, and ensure its social impact.

A multinational cohort study uncovered sex differences in excess mortality after kidney transplant.

Worldwide and at all ages, males have a higher mortality risk than females. This mortality bias should be preserved in kidney transplant recipients unless there are sex differences in the effects of transplantation. Here we compared the excess risk of mortality (risk above the general population) in female versus male recipients of all ages recorded in three large transplant databases. This included first deceased donor kidney transplant recipients and accounted for the modifying effects of donor sex and recipient age. After harmonization of variables across cohorts, relative survival models were fitted in each cohort separately and results were combined using individual patient data meta-analysis among 466,892 individuals (1988-2019). When the donor was male, female recipients 0-12 years (Relative Excess Risk 1.54, 95% Confidence Interval 1.20-1.99), 13-24 years (1.17, 1.01-1.34), 25-44 years (1.11, 1.05-1.18) and 60 years and older (1.05, 1.02-1.08) showed higher excess mortality risks than male recipients of the same age. When the donor was female, the Relative Excess Risk for those over 12 years were similar to those when the donor was male. There is a higher excess mortality risk in female than male recipients with differences larger at younger than older ages and only statistically significant when the donor was male. While these findings may be partly explained by the known sex differences in graft loss risks, sex differences in the risks of death with graft function may also contribute. Thus, higher risks in females than males suggest that management needs to be modified to optimize transplant outcomes among females.