Expression of Resistin, Chemerin, and Chemerin's Receptor in the Unstable Carotid Atherosclerotic Plaque.

Background and Purpose: Unstable carotid plaques are a common cause of ischemic strokes. Identifying markers that reflect/contribute to plaque instability has become a prominent focus in cardiovascular research. The adipokines, resistin and chemerin, and ChemR23 (chemerin receptor), may play a role in carotid atherosclerosis, making them potential candidates to assess plaque instability. However, the expression and interrelationship of resistin and chemerin (and ChemR23) protein and mRNA within the carotid atherosclerotic plaque remains elusive. Thus, we investigated herein, the association between plaque mRNA and protein expression of resistin and chemerin (and ChemR23) and carotid plaque instability in humans, and whether sex differences exist in the relationship between these adipokines and plaque instability. Methods: Human carotid plaques were processed for immunohistochemical/mRNA analysis of resistin, chemerin, and ChemR23. Plaque instability was assessed by gold-standard histological classifications. A semi-quantitative scoring system was used to determine the intensity of adipokine expression on macrophages/foam cells, as well as the percentage of inflammatory cells stained positive. Plaque adipokine protein expression was also digitally quantified and mRNA expression was assessed by qRT-PCR. Results: Resistin and chemerin mRNA expression was 80% and 32% lower, respectively, in unstable versus stable plaques (P<0.05), while no difference in ChemR23 mRNA expression was observed. In contrast, greater resistin staining intensity and percentage of cells stained positive were detected in unstable versus stable plaques (P<0.01). Similarly, chemerin and ChemR23 staining intensity and percentage of cells stained were positively associated with plaque instability (P<0.05). No strong sex-specific relationship was observed between adipokines and plaque instability. Conclusions: This study examined the relationship between resistin, chemerin, and ChemR23, and carotid plaque instability, with a specific analysis at the plaque level. We reported a positive association between plaque instability and protein levels of resistin, chemerin, and ChemR23 but a negative association with resistin and chemerin mRNA expression. This suggests these adipokines exert proinflammatory roles in the process of carotid atherosclerosis and may be regulated via a negative feedback regulatory mechanism.

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.

The Use of Kidneys With Lower Longevity From Deceased Donors to Improve Access to Preemptive Renal Transplantation for Elderly Patients: A Qualitative Study.

Background: There is a gap between the number of patients waiting for a transplant and the number of kidneys available. Some deceased donor kidneys are currently nonutilized, as medical teams fear that they will experience suboptimal graft survival. However, these organs could provide an acceptable therapeutic option if they were allocated for preemptive kidney transplantation in elderly candidates. Objective: This project aims to gather patients' perspectives on the allocation of kidneys with lower longevity for preemptive kidney transplantation in elderly patients. Design: Individual interviews. Setting: The Center hospitalier de l'Université de Montréal (CHUM) chronic kidney disease (CKD) clinic. Participants: Patients aged between 64 and 75 years with CKD G4-5 ND, followed at the CHUM and who have not initiated dialysis yet. Methods: Between March and July 2023, we conducted 14 individual interviews with patients aged between 64 and 75 years who had CKD G4-5 ND and were followed at the CHUM. The interviews were digitally recorded and transcribed. Thematic analysis was conducted. Results: Most participants were in favor of using kidneys with lower longevity to increase their access to transplantation, improve their quality of life, enable accelerated transplantation, and avoid dialysis. Patients also wanted to be engaged in the decision-making process, underlining the importance of informed consent. Although the use of kidneys with lower longevity offers the hope of returning to "normal" life, some patients were concerned about the risk of reduced graft survival and the need for a subsequent kidney transplant. In these cases, patients were interested in using mitigation strategies, such as prioritization for kidney transplantation from standard donors in case of early graft loss associated with receiving kidneys with lower longevity. They also recommended the development of a separate waiting list for patients consenting to preemptive transplantation with kidneys with lower longevity. Limitations: This study was conducted in only 1 nephrology clinic in the province of Quebec with French-speaking patients. Consequently, the results may not be generalizable to other populations, including ethnic minorities. Conclusion: The use of kidneys with lower longevity for preemptive kidney transplantation appears to be an interesting option for elderly kidney transplant candidates. However, patient information and participation in the decision-making process are essential. Moreover, organ donation organizations and transplant programs should develop a separate waitlist for transplant candidates who have preconsented to receive organ offers of deceased donor kidneys with lower longevity. Trial registration: Not registered.

Mise en contexte: Il existe un écart entre le nombre de patients en attente d'une greffe et le nombre de reins disponibles. À l'heure actuelle, un certain nombre de reins de donneurs décédés ne sont pas utilisés, car les équipes médicales craignent que la survie des greffons ne soit pas optimale. Ces organes pourraient toutefois constituer une option thérapeutique acceptable s'ils étaient attribués à des candidats âgés pour une transplantation pré-emptive. Objectifs de l'étude: Ce projet vise à connaître la position des patients quant à la transplantation pré-emptive de reins jugés de moindre longévité chez des candidats âgés. Conception: Entretiens individuels. Cadre: La clinique d'insuffisance rénale chronique du Center hospitalier de l'Université de Montréal (CHUM). Sujets: Des patients âgés de 64 à 75 ans atteints d'IRC G4-5 suivis au CHUM et n'ayant pas encore amorcé la dialyse. Méthodologie: Entre mars et juillet 2023, nous avons mené 14 entretiens individuels avec des patients de 64 à 75 ans non dialysés atteints d'IRC G4-5 suivis au CHUM. Les entrevues ont été enregistrées sous forme numérique, puis transcrites. Une analyze thématique a été effectuée. Résultats: La plupart des personnes interrogées étaient en faveur de l'utilisation de reins de moindre longévité en vue d'augmenter leur accès à la transplantation, d'améliorer leur qualité de vie, d'accélérer la transplantation et d'éviter la dialyse. Les patients souhaitaient également participer au processus décisionnel, ce qui met en lumière l'importance du consentement éclairé. Bien que l'utilisation de reins de moindre longévité offre l'espoir d'un retour à une vie « normale ¼, certains patients s'inquiétaient du risque de survie réduite du greffon et, dès lors, de l'éventuelle nécessité d'une nouvelle greffe. Dans ces cas, les personnes interrogées étaient intéressées par des stratégies d'atténuation comme une priorité donnée à la transplantation de reins provenant de donneurs standards en cas de perte précoce du greffon liée au fait d'avoir reçu un rein de moindre longévité. Les personnes répondantes ont également proposé l'établissement d'une liste d'attente distincte pour les patients qui consentent à une transplantation pré-emptive avec des reins de moindre longévité. Limites de l'étude: Cette étude a été menée dans une seule clinique de néphrologie au Québec auprès de patients francophones. Par conséquent, les résultats pourraient ne pas être généralisables à d'autres populations, notamment à des personnes issues de minorités ethniques. Conclusion: L'utilisation de reins de moindre longévité pour la transplantation rénale pré-emptive semble être une option thérapeutique intéressante pour les candidats âgés. Toutefois, il est essentiel que les patients soient bien informés et qu'ils participent au processus décisionnel. Enfin, les organismes de don d'organes et les programs de transplantation devraient établir une liste d'attente distincte pour les candidats ayant préalablement consenti à recevoir des offres d'organes pour des reins de moindre longévité provenant de donneurs décédés.