Sex-Related Disparities in Cardiovascular Outcomes Among Older Adults With Late-Onset Hypertension.

BACKGROUND: It is unclear whether sex-based differences in cardiovascular outcomes exist in late-onset hypertension. METHODS: This is a population-based cohort study in Ontario, Canada of 266 273 adults, aged ≥66 years with newly diagnosed hypertension. We determined the incidence of the primary composite cardiovascular outcome (myocardial infarction, stroke, and congestive heart failure), all-cause mortality, and cardiovascular death by sex using Cox proportional hazard models adjusted for demographic factors and comorbidities. RESULTS: The mean age of the total cohort was 74 years, and 135 531 (51%) were female. Over a median follow-up of 6.6 (4.7-9.0) years, females experienced a lower crude incidence rate (per 1000 person-years) than males for the primary composite cardiovascular outcome (287.3 versus 311.7), death (238.4 versus 251.4), and cardiovascular death (395.7 versus 439.6), P<0.001. The risk of primary composite cardiovascular outcome was lower among females (adjusted hazard ratio, 0.75 [95% CI, 0.73-0.76]; P<0.001) than in males. This was consistent after adjusting for the competing risk of all-cause death with a subdistributional hazard ratio, 0.88 ([95% CI, 0.86-0.91]; P<0.001). CONCLUSIONS: Females had a lower risk of cardiovascular outcomes compared with males within a population characterized by advanced age and new hypertension. Our results highlight that the severity of outcomes is influenced by sex in relation to the age at which hypertension is diagnosed. Further studies are required to identify sex-specific variations in the diagnosis and management of late-onset hypertension due to its high incidence in this group.

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.

Association Between First Post-operative Day Urine Output Following Kidney Transplantation and Short-Term and Long-Term Outcomes: A Retrospective Cohort Study.

Background: The relationship between post-operative urine output (UO) following kidney transplantation and long-term graft function has not been well described. Objective: In this study, we examined the association between decreased UO on post-operative day 1 (POD1) and post-transplant outcomes. Design: This is a retrospective cohort study. Setting: Atlantic Canada. Patients: Patients from the 4 Atlantic Canadian provinces (Nova Scotia, New Brunswick, Newfoundland, and Prince Edward Island) who received a live or deceased donor kidney transplant from 2006 through 2019 through the multiorgan transplant program at the Queen Elizabeth II Health Sciences Centre (QEII) hospital in Halifax, Nova Scotia. Measurements: Using multivariable Cox proportional hazards models, we assessed the association of low POD1 UO (defined as ≤1000 mL) with death-censored graft loss (DCGL). In secondary analyses, we used adjusted logistic regression or Cox models as appropriate to assess the impact of UO on delayed graft function (DGF), prolonged length of stay (greater than the median for the entire cohort), and death. Results: Of the 991 patients included, 151 (15.2%) had a UO ≤1000 mL on POD1. Low UO was independently associated with DCGL (hazard ratio [HR] = 4.00, 95% confidence interval [CI] = 95% CI = 1.55-10.32), DGF (odds ratio [OR] = 45.25, 95% CI = 23.00-89.02), and prolonged length of stay (OR = 5.06, 95% CI = 2.95-8.69), but not death (HR = 0.81, 95% CI = 0.31-2.09). Limitations: This was a single-center, retrospective, observational study and therefore has inherent limitations of generalizability, data collection, and residual confounding. Conclusions: Overall, reduced post-operative UO following kidney transplantation is associated with an increased risk of DCGL, DGF, and prolonged hospital length of stay.

Contexte: Le lien entre la diurèse postopératoire après une transplantation rénale et la fonction du greffon à long terme n'a pas été bien décrit. Objectif: Dans cette étude, nous avons examiné l'association entre la diminution de la diurèse au jour 1 postopératoire et les résultats après la transplantation. Conception: Étude de cohorte rétrospective. Cadre: Canada atlantique. Patients: Des patients des quatre provinces du Canada atlantique (Nouvelle-Écosse, Nouveau-Brunswick, Terre-Neuve et Île-du-Prince-Édouard) ayant reçu une greffe de rein provenant d'un donneur vivant ou décédé entre 2006 et 2019 dans le cadre du programme de transplantation multiorganes de l'hôpital QEII d'Halifax (Nouvelle-Écosse). Mesures: À l'aide de modèles à risques proportionnels de Cox multivariés, nous avons évalué l'association entre une faible diurèse (définie comme ≤ 1 000 ml) et la perte du greffon censurée par le décès (PGCD). Dans les analyses secondaires, nous avons utilisé des modèles de Cox ou des modèles de régression logistique ajustés, selon le cas, pour évaluer l'effet de la diurèse sur la fonction retardée du greffon, la durée prolongée du séjour (supérieure à la médiane pour l'ensemble de la cohorte) et le décès. Résultats: Des 991 patients inclus, 151 (15,2%) présentaient une diurèse inférieure à 1 000 ml au jour 1 postopératoire. Une faible diurèse a été indépendamment associée à la PGCD (rapport de risque [RR]: 4,00; IC 95 %: 1,55-10,32), à une fonction retardée du greffon (rapport de cotes [RC]: 45,25; IC 95 %: 23,00-89,02) et à un séjour prolongé à l'hôpital (RC: 5,06; IC 95 %: 2,95-8,69), mais pas au décès (RR: 0,81; IC 95 %: 0,31-2,09). Limites: Il s'agissait d'une étude observationnelle rétrospective monocentrique. L'étude présente ainsi des limites inhérentes à la généralisabilité, à la collecte des données et aux facteurs confondants résiduels. Conclusion: Dans l'ensemble, une diminution de la diurèse postopératoire après une transplantation rénale est associée à un risque accru de PGCD et de fonction retardée du greffon, ainsi qu'à un séjour prolongé à l'hôpital.

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.

Patient and Provider Gender and Kidney Transplant Referral in Canada: A Survey of Canadian Healthcare Providers.

BACKGROUND: Referral for kidney transplant (KT) is variable, with women often disadvantaged. This study aimed to better characterize Canadian transplant referral practices and identify potential differences by respondent and/or patient gender using surveys targeted at healthcare practitioners (HCPs) involved in KT. METHODS: Surveys consisting of 25 complex patient cases representing 7 themes were distributed to KT HCPs across Canada (March 3, 2022-April 27, 2022) using national nephrology/transplant society email registries. Respondents were asked whether they would refer the patient for transplant. Two identical surveys were created, differing only by gender/gender pronouns used in each case. Multivariable logistic regression was used to assess the association of respondent demographics and patient themes (including case gender) with the odds of transplant referral (overall and stratifying by respondent gender). RESULTS: Overall, the referral rate was 58.0% among 97 survey respondents (46.4% male). Case themes associated with a lower likelihood of referral included adherence concerns (adjusted odds ratio [aOR] 0.65; 95% confidence interval [CI], 0.45-0.94), medical complexity (aOR 0.57; 95% CI, 0.38-0.85), and perceived frailty (aOR 0.63; 95% CI, 0.47-0.84). Respondent gender was not associated with differences in KT referral (aOR 0.91; 95% CI, 0.65-1.26 for male versus female respondents) but modified the association of frailty (less referral for male than female respondents, P = 0.005) and medical complexity (less referral for female than male respondents, P = 0.009) with referral. There were no differences in referral rate by case gender ( P = 0.82). CONCLUSIONS: KT referral practices vary among Canadian HCPs. In this study, there were no differences in likelihood of transplant referral by candidate gender.

The Impact of Combined Warm and Cold Ischemia Time on Post-transplant Outcomes.

Background: Prolonged warm ischemia time (WIT) and cold ischemia time (CIT) are independently associated with post-transplant graft failure; their combined impact has not been previously studied. We explored the effect of combined WIT/CIT on all-cause graft failure following kidney transplantation. Methods: The Scientific Registry of Transplant Recipients was used to identify kidney transplant recipients from January 2000 to March 2015 (after which WIT was no longer separately reported), and patients were followed until September 2017. A combined WIT/CIT variable (excluding extreme values) was separately derived for live and deceased donor recipients using cubic splines; for live donor recipients, the reference group was WIT 10 to <23 minutes and CIT >0 to <0.42 hours, and for deceased donor recipients the WIT was 10 to <25 minutes and CIT 1 to <7.75 hours. The adjusted association between combined WIT/CIT and all-cause graft failure (including death) was analyzed using Cox regression. Secondary outcomes included delayed graft function (DGF). Results: A total of 137 125 recipients were included. For live donor recipients, patients with prolonged WIT/CIT (60 to ≤120 minutes/3.04 to ≤24 hours) had the highest adjusted hazard ratio (HR) for graft failure (HR = 1.61, 95% confidence interval [CI] = 1.14-2.29 relative to the reference group). For deceased donor recipients, a WIT/CIT of 63 to ≤120 minutes/28 to ≤48 hours was associated with an adjusted HR of 1.35 (95% CI = 1.16-1.58). Prolonged WIT/CIT was also associated with DGF for both groups although the impact was more driven by CIT. Conclusions: Combined WIT/CIT is associated with graft loss following transplantation. Acknowledging that these are separate variables with different determinants, we emphasize the importance of capturing WIT and CIT independently. Furthermore, efforts to reduce WIT and CIT should be prioritized.

Contexte: La période prolongée d'ischémie à chaud (WIT­warm ischemia time) et la période prolongée d'ischémie à froid (CIT­cold ischemia time) ont été associées de façon indépendante à une défaillance du greffon post-transplantation, mais leur effet combiné n'a jamais été étudié. Nous avons examiné l'effet combiné WIT/CIT sur la défaillance du greffon toutes causes confondues après une transplantation rénale. Méthodologie: Le Scientific Registry of Transplant Recipients a été utilisé pour identifier les receveurs d'une greffe de rein entre janvier 2000 et mars 2015 (date après laquelle la WIT n'a plus été rapportée séparément). Les patients ont été suivis jusqu'en septembre 2017. Une variable combinée WIT/CIT (excluant les valeurs extrêmes) a été dérivée de façon isolée pour les donneurs vivants et les donneurs décédés à l'aide d'une fonction spline cubique. La WIT du groupe référence pour les donneurs vivants se situait entre 10 et <23 minutes, et la CIT entre 0 et <0,42 heure; pour les donneurs décédés, la WIT se situait entre 10 et <25 minutes, et la CIT entre 1 et <7,75 heures. L'association corrigée entre une combinaison WIT/CIT et la défaillance du greffon toutes causes confondues (y compris le décès) a été analysée à l'aide de la régression de Cox. Les résultats secondaires incluaient une reprise retardée de la fonction du greffon (RRFG). Résultats: Un total de 137 125 receveurs d'un rein a été inclus. Dans le groupe des receveurs d'un organe provenant d'un donneur vivant, les patients avec une WIT/CIT prolongée (60 à ≤120 minutes/3,04 à ≤24 heures) présentaient un risque relatif corrigé plus élevé de défaillance du greffon (RRc: 1,61; IC 95 %: 1,14-2,29) par rapport au groupe de référence. Dans le groupe des receveurs d'un organe provenant d'un donneur décédé, une combinaison WIT/CIT de 63 à ≤120 minutes/28 à ≤48 heures a été associée à un RRc de 1,35 (IC 95 %: 1,16-1,58). La WIT/CIT prolongée a également été associée à une RRFG pour les deux groupes, bien que cet effet ait été davantage influencé par la CIT. Conclusion: La combinaison WIT/CIT est associée à la perte du greffon après la transplantation. Sachant qu'il s'agit de variables distinctes avec des déterminants différents, nous soulignons l'importance de rapporter la WIT et la CIT de façon indépendante. Qui plus est, les efforts visant à réduire la WIT et la CIT devraient être prioritaires.

Patterns in Use and Transplant Outcomes Among Adult Recipients of Kidneys From Deceased Donors With COVID-19.

Importance: While the COVID-19 pandemic enters a new phase and the proportion of individuals with a previous COVID-19 diagnosis increases, the national patterns in kidney use and medium-term kidney transplant (KT) outcomes among patients receiving kidneys from active or resolved COVID-19-positive donors remain unknown. Objective: To evaluate the patterns in kidney use and KT outcomes among adult recipients of kidneys from deceased donors with active or resolved COVID-19. Design, Setting, and Participants: This retrospective cohort study was conducted using national US transplant registry data from 35 851 deceased donors (71 334 kidneys) and 45 912 adult patients who received KTs from March 1, 2020, to March 30, 2023. Exposure: The exposure was donor SARS-CoV-2 nucleic acid amplification test (NAT) results, with positive NAT results within 7 days before procurement defined as active COVID-19 and positive NAT results 1 week (>7 days) before procurement defined as resolved COVID-19. Main Outcomes and Measures: Primary outcomes were kidney nonuse, all-cause kidney graft failure, and all-cause patient death. Secondary outcomes were acute rejection (ie, rejection in the first 6 months after KT), transplant hospitalization length of stay (LOS), and delayed graft function (DGF). Multivariable logistic regression analyses were performed for kidney nonuse, rejection, and DGF; multivariable linear regression analyses were performed for LOS; and multivariable Cox regression analyses were performed for graft failure and all-cause death. All models were adjusted for inverse probability treatment weighting. Results: Among 35 851 deceased donors, the mean (SD) age was 42.5 (15.3) years; 22 319 (62.3%) were men and 23 992 (66.9%) were White. Among 45 912 recipients, the mean (SD) age was 54.3 (13.2) years; 27 952 (60.9%) were men and 15 349 (33.4%) were Black. The likelihood of nonuse of kidneys from active or resolved COVID-19-positive donors decreased over time. Overall, kidneys from active COVID-19-positive donors (adjusted odds ratio [AOR], 1.55; 95% CI, 1.38-1.76) and kidneys from resolved COVID-19-positive donors (AOR, 1.31; 95% CI, 1.16-1.48) had a higher likelihood of nonuse compared with kidneys from COVID-19-negative donors. From 2020 to 2022, kidneys from active COVID-19-positive donors (2020: AOR, 11.26 [95% CI, 2.29-55.38]; 2021: AOR, 2.09 [95% CI, 1.58-2.79]; 2022: AOR, 1.47 [95% CI, 1.28-1.70]) had a higher likelihood of nonuse compared with kidneys from donors without COVID-19. Kidneys from resolved COVID-19-positive donors had a higher likelihood of nonuse in 2020 (AOR, 3.87; 95% CI, 1.26-11.90) and 2021 (AOR, 1.94; 95% CI, 1.54-2.45) but not in 2022 (AOR, 1.09; 95% CI, 0.94-1.28). In 2023, kidneys from both active COVID-19-positive donors (AOR, 1.07; 95% CI, 0.75-1.63) and resolved COVID-19-positive donors (AOR, 1.18; 95% CI, 0.80-1.73) were not associated with higher odds of nonuse. No higher risk of graft failure or death was found in patients receiving kidneys from active COVID-19-positive donors (graft failure: adjusted hazard ratio [AHR], 1.03 [95% CI, 0.78-1.37]; patient death: AHR, 1.17 [95% CI, 0.84-1.66]) or resolved COVID-19-positive donors (graft failure: AHR, 1.10 [95% CI, 0.88-1.39]; patient death: AHR, 0.95 [95% CI, 0.70-1.28]). Donor COVID-19 positivity was not associated with longer LOS, higher risk of acute rejection, or higher risk of DGF. Conclusions and Relevance: In this cohort study, the likelihood of nonuse of kidneys from COVID-19-positive donors decreased over time, and donor COVID-19 positivity was not associated with worse KT outcomes within 2 years after transplant. These findings suggest that the use of kidneys from donors with active or resolved COVID-19 is safe in the medium term; further research is needed to assess longer-term transplant outcomes.

Hormone replacement therapy and COVID-19 outcomes in solid organ transplant recipients compared with the general population.

Exogenous estrogen is associated with reduced coronavirus disease (COVID) mortality in nonimmunosuppressed/immunocompromised (non-ISC) postmenopausal females. Here, we examined the association of estrogen or testosterone hormone replacement therapy (HRT) with COVID outcomes in solid organ transplant recipients (SOTRs) compared to non-ISC individuals, given known differences in sex-based risk in these populations. SOTRs ≥45 years old with COVID-19 between April 1, 2020 and July 31, 2022 were identified using the National COVID Cohort Collaborative. The association of HRT use in the last 24 months (exogenous systemic estrogens for females; testosterone for males) with major adverse renal or cardiac events in the 90 days post-COVID diagnosis and other secondary outcomes were examined using multivariable Cox proportional hazards models and logistic regression. We repeated these analyses in a non-ISC control group for comparison. Our study included 1135 SOTRs and 43 383 immunocompetent patients on HRT with COVID-19. In non-ISC, HRT use was associated with lower risk of major adverse renal or cardiac events (adjusted hazard ratio [aHR], 0.61; 95% confidence interval [CI], 0.57-0.65 for females; aHR, 0.70; 95% CI, 0.65-0.77 for males) and all secondary outcomes. In SOTR, HRT reduced the risk of acute kidney injury (aHR, 0.79; 95% CI, 0.63-0.98) and mortality (aHR, 0.49; 95% CI, 0.28-0.85) in males with COVID but not in females. The potentially modifying effects of immunosuppression on the benefits of HRT requires further investigation.

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.

Community risks for SARS-CoV-2 infection among fully vaccinated US adults by rurality: A retrospective cohort study from the National COVID Cohort Collaborative.

BACKGROUND: While COVID-19 vaccines reduce adverse outcomes, post-vaccination SARS-CoV-2 infection remains problematic. We sought to identify community factors impacting risk for breakthrough infections (BTI) among fully vaccinated persons by rurality. METHODS: We conducted a retrospective cohort study of US adults sampled between January 1 and December 20, 2021, from the National COVID Cohort Collaborative (N3C). Using Kaplan-Meier and Cox-Proportional Hazards models adjusted for demographic differences and comorbid conditions, we assessed impact of rurality, county vaccine hesitancy, and county vaccination rates on risk of BTI over 180 days following two mRNA COVID-19 vaccinations between January 1 and September 21, 2021. Additionally, Cox Proportional Hazards models assessed the risk of infection among adults without documented vaccinations. We secondarily assessed the odds of hospitalization and adverse COVID-19 events based on vaccination status using multivariable logistic regression during the study period. RESULTS: Our study population included 566,128 vaccinated and 1,724,546 adults without documented vaccination. Among vaccinated persons, rurality was associated with an increased risk of BTI (adjusted hazard ratio [aHR] 1.53, 95% confidence interval [CI] 1.42-1.64, for urban-adjacent rural and 1.65, 1.42-1.91, for nonurban-adjacent rural) compared to urban dwellers. Compared to low vaccine-hesitant counties, higher risks of BTI were associated with medium (1.07, 1.02-1.12) and high (1.33, 1.23-1.43) vaccine-hesitant counties. Compared to counties with high vaccination rates, a higher risk of BTI was associated with dwelling in counties with low vaccination rates (1.34, 1.27-1.43) but not medium vaccination rates (1.00, 0.95-1.07). Community factors were also associated with higher odds of SARS-CoV-2 infection among persons without a documented vaccination. Vaccinated persons with SARS-CoV-2 infection during the study period had significantly lower odds of hospitalization and adverse events across all geographic areas and community exposures. CONCLUSIONS: Our findings suggest that community factors are associated with an increased risk of BTI, particularly in rural areas and counties with high vaccine hesitancy. Communities, such as those in rural and disproportionately vaccine hesitant areas, and certain groups at high risk for adverse breakthrough events, including immunosuppressed/compromised persons, should continue to receive public health focus, targeted interventions, and consistent guidance to help manage community spread as vaccination protection wanes.

Predictors of Urgent Dialysis Following Ambulance Transport to the Emergency Department in Patients Treated With Maintenance Hemodialysis.

Background: Patients receiving maintenance hemodialysis frequently require ambulance transport to the emergency department (ambulance-ED transport). Identifying predictors of outcomes after ambulance-ED transport, especially the need for timely dialysis, is important to health care providers. Objective: The purpose of this study was to derive a risk-prediction model for urgent dialysis after ambulance-ED transport. Design: Observational cohort study. Setting and Patients: All ambulance-ED transports among incident and prevalent patients receiving maintenance hemodialysis affiliated with a regional dialysis program (catchment area of approximately 750 000 individuals) from 2014 to 2018. Measurements: Patients' vital signs (systolic blood pressure, oxygen saturation, respiratory rate, and heart rate) at the time of paramedic transport and time since last dialysis were utilized as predictors for the outcome of interest. The primary outcome was urgent dialysis (defined as dialysis in a monitored setting within 24 hours of ED arrival or dialysis within 24 hours with the first ED patient blood potassium level >6.5 mmol/L) for an unscheduled indication. Secondary outcomes included, hospitalization, hospital length of stay, and in-hospital mortality. Methods: A logistic regression model to predict outcomes of urgent dialysis. Discrimination and calibration were assessed using the C-statistic and Hosmer-Lemeshow test. Results: Among 878 ED visits, 63 (7.2%) required urgent dialysis. Hypoxemia (odds ratio [OR]: 4.04, 95% confidence interval [CI]: 1.75-9.33) and time from last dialysis of 24 to 48 hours (OR: 3.43, 95% CI: 1.05-11.9) and >48 hours (OR: 9.22, 95% CI: 3.37-25.23) were strongly associated with urgent dialysis. A risk-prediction model incorporating patients' vital signs and time from last dialysis had good discrimination (C-statistic 0.8217) and calibration (Hosmer-Lemeshow goodness of fit P value .8899). Urgent dialysis patients were more likely to be hospitalized (63% vs 34%), but there were no differences in inpatient mortality or length of stay. Limitations: Missing data, requires external validation. Conclusion: We derived a risk-prediction model for urgent dialysis that may better guide appropriate transport and care for patients requiring ambulance-ED transport.

Contexte: Les patients sous hémodialyse chronique doivent souvent être transportés au service des urgences par ambulance (transport ambulance-SU). Il est important pour les prestataires de soins de santé que l'on détermine les facteurs prédictifs des résultats après un transport ambulance-SU, en particulier le besoin de dialyze d'urgence. Objectifs: Cette étude visait à établir un modèle de prédiction du risque pour une dialyze d'urgence après un transport ambulance-SU. Type d'étude: Étude de cohorte observationnelle. Participants et cadre de l'étude: Tous les transports ambulance-SU de patients incidents et prévalents recevant une hémodialyse chronique affiliée à un program régional de dialyze (zone desservant environ 750 000 personnes) entre 2014 et 2018. Prédicteurs: Les signes vitaux du patient (pression artérielle systolique, saturation en oxygène, fréquence respiratoire et fréquence cardiaque) au moment du transport par ambulance et le temps écoulé depuis la dernière dialyze. Résultats: La dialyze d'urgence (définie comme une dialyze en environnement monitoré dans les 24 heures suivant l'arrivée aux urgences ou une dialyze dans les 24 heures avec une première mesure du taux de potassium sanguin aux urgences supérieure à 6,5 mmol/L) pour une indication non programmée. Résultats secondaires: hospitalization, durée du séjour à l'hôpital et mortalité à l'hôpital. Méthodologie: Un modèle de régression logistique a servi à prédire le résultat de dialyze d'urgence. La discrimination et la calibration ont été évalués à l'aide de la statistique C et du test Hosmer-Lemeshow. Résultats: Parmi les 878 visites aux urgences, 63 (7,2 %) ont nécessité une dialyze d'urgence. L'hypoxémie (rapport de cote [RC]: 4,04; IC à 95 %: 1,75-9,33) et des périodes de 24 à 48 heures (RC: 3,43; IC à 95 %: 1,05-11,9) et de plus de 48 heures (RC: 9,22; IC à 95 %: 3,37-25,23) depuis la dernière dialyze sont les facteurs qui ont été les plus fortement associés à une dialyze d'urgence. Un modèle de prédiction du risque intégrant les signes vitaux du patient et le temps depuis la dernière dialyze a présenté une bonne discrimination (statistique C: 0,8217) et une bonne calibration (qualité de l'ajustement selon Hosmer-Lemeshow: P =,8899). Les patients qui avaient reçu une dialyze d'urgence étaient plus susceptibles d'être hospitalisés (63% contre 34%), mais aucune différence n'a été observée pour le taux de mortalité ou la durée du séjour en milieu hospitalier. Limites: Données manquantes, validation externe requise. Conclusion: Nous avons dérivé un modèle de prédiction du risque de dialyze d'urgence susceptible de mieux guider le transport et les soins appropriés pour les patients nécessitant un transport ambulance-SU.

The Association of Pre-Transplant C-Peptide Level with the Development of Post-Transplant Diabetes: A Cohort Study.

Background: Post-transplant diabetes mellitus (PTDM) is an important complication after kidney transplantation that results in reduced patient and allograft survival. Although there are established risk factors for PTDM, whether pretransplant C-peptide levels associate with PTDM is unknown. Therefore, in this study, we aimed to examine the association of pretransplant C-peptide levels with PTDM. Methods: This was a cohort study of nondiabetic adult patients who underwent kidney transplant in Nova Scotia, Canada, between January 1, 2016, and March 31, 2021, with fasting C-peptide levels measured before transplant. Multivariable logistic regression was used to determine the association of pretransplant C-peptide (dichotomized around the median) with PTDM at 1 year post transplant. Given the known association between pretransplant obesity and PTDM, we repeated our primary analysis in a cohort restricted to a BMI of 20-35 kg/m2. Results: The median C-peptide value was 3251 (Q1 2480, Q3 4724); pretransplant C-peptide level was dichotomized at 3000 pmol/L. PTDM occurred in 25 (19%) individuals. Thirty percent of patients in the high and only 2% of patients in the low C-peptide groups developed PTDM (P<0.001). A C-peptide level ≥3000 pmol/L was strongly associated with PTDM in multivariable analysis (OR=18.9, 95% CI, 2.06 to 174.2). In a restricted cohort with a BMI of 20-35 kg/m2, an elevated pretransplant C-peptide remained independently associated with the risk of PTDM (OR=15.7, 95% CI, 1.64 to 150.3). C-peptide was the only factor independently associated with PTDM in this restricted BMI cohort. Conclusions: A pretransplant C-peptide level ≥3000 pmol/L was associated with a nearly 20-fold increased odds of PTDM at 1 year post kidney transplantation. Identifying patients with high pretransplant C-peptide levels may therefore help identify those at risk for PTDM who may benefit from focused preventative and therapeutic interventions and support.

Combined Donor-Recipient Obesity and the Risk of Graft Loss After Kidney Transplantation.

Background: As the prevalence of obesity increases globally, appreciating the effect of donor and recipient (DR) obesity on graft outcomes is of increasing importance. Methods: In a cohort of adult, kidney transplant recipients (2000-2017) identified using the SRTR, we used Cox proportional hazards models to examine the association between DR obesity pairing (body mass index (BMI) >30 kg/m2), and death-censored graft loss (DCGL) or all-cause graft loss, and logistic regression to examine risk of delayed graft function (DGF) and ≤30 days graft loss. We also explored the association of DR weight mismatch (>30 kg, 10-30 kg (D>R; D

Comparing the Net Benefits of Adult Deceased Donor Kidney Transplantation for a Patient on the Preemptive Waiting List vs a Patient Receiving Dialysis.

Importance: Preemptive kidney transplantation is the preferred treatment for end-stage kidney disease. However, deceased donor (DD) kidneys are limited, and the net benefit of allocating kidneys to a preemptively waitlisted patient rather than to a patient receiving dialysis is unclear. Objective: To estimate the net benefit and costs of allocating kidneys to preemptively waitlisted patients vs those receiving dialysis. Design, Setting, and Participants: This medical decision analytical model used data from the 2020 US Renal Data System to calculate patient survival among waitlisted patients who received a DD kidney transplant. Four patients were simulated, with similar characteristics: (1) a patient on the preemptive waiting list receiving a DD transplant, (2) a patient on the preemptive waiting list never receiving a transplant, (3) a waitlisted patient already receiving dialysis (dialysis vintage <1 year) receiving a transplant, and (4) a waitlisted patient already receiving dialysis (dialysis vintage <1 year) never receiving a transplant. Annual probability of initiating dialysis (for patients 1 and 2) and duration of dialysis (for patients 3 and 4) were varied in sensitivity analyses. Exposures: Allocating a DD kidney to a patient on the preemptive waiting list vs the same kidney to a patient receiving dialysis for less than 1 year, with similar recipient characteristics. Main Outcomes and Measures: Differences in projected quality-adjusted life-years (QALYs) and total costs. Results: In a simulated patient with a mean start age of 50 years (range, 30-64 years), the patient receiving a preemptive DD transplantation experienced 10.58 (95% CI, 10.36-10.80) QALYs, and the patient on the preemptive waiting list never transplanted experienced 6.83 (95% CI, 6.67-6.99) QALYs. The patient receiving DD transplantation after less than 1 year of dialysis experienced 10.33 (95% CI, 10.21-10.55) QALYs, and the patient receiving dialysis who remained on the waiting list experienced 6.20 (95% CI, 6.04-6.36) QALYs; allocating a DD kidney to the preemptive patient added 3.75 (95% CI, 3.57-3.93) QALYs, whereas allocating the kidney to the patient already receiving dialysis added 4.13 (95% CI, 3.92-4.31) QALYs. While the estimated posttransplant survival was longest for the preemptive transplant recipient, preferentially allocating the kidney to the preemptive patient results in 0.39 (95% CI, 0.49-0.29) fewer QALYs. The net cost of preemptive transplantation was $54 100 (95% CI, $44 100-$64 100) more than transplantation to a waitlisted patient. If the rate of transitioning to dialysis was 20 (rather than 33) events per 100 patient waiting list-years, the net QALYs were -0.67 (95% CI, -0.78 to -0.56). If the patient was receiving dialysis for 3 to 4 years (vs <1 year) the net benefit was not significantly different; however, net costs were considerably higher for the preemptive option. Conclusions and Relevance: In this decision analytic model study, although allocating DD kidneys to patients preemptively was the best option from a patient perspective, allocating DD kidneys to patients receiving dialysis was a better use of a scare resource from a societal perspective.

Predictors of Hyperkalemia among Patients on Maintenance Hemodialysis Transported to the Emergency Department by Ambulance.

Background: Hyperkalemia is common among patients on maintenance hemodialysis (HD) and is associated with mortality. We hypothesized that clinical characteristics available at time of paramedic assessment before emergency department (ED) ambulance transport (ambulance-ED) would associate with severe hyperkalemia (K≥6 mmol/L). Rapid identification of patients who are at risk for hyperkalemia and thereby hyperkalemia-associated complications may allow paramedics to intervene in a timely fashion, including directing emergency transport to dialysis-capable facilities. Methods: Patients on maintenance HD from a single paramedic provider region, who had at least one ambulance-ED and subsequent ED potassium from 2014 to 2018, were examined using multivariable logistic regression to create risk prediction models inclusive of prehospital vital signs, days from last dialysis, and the presence of prehospital electrocardiogram (ECG) features of hyperkalemia. We used bootstrapping with replacement to validate each model internally, and performance was assessed by discrimination and calibration. Results: Among 704 ambulance-ED visits, severe hyperkalemia occurred in 75 (11%); 26 patients with ED hyperkalemia did not have a prehospital ECG. Younger age at transport, longer HD vintage, more days from last hemodialysis session (OR=49.84; 95% CI, 7.72 to 321.77 for ≥3 days versus HD the same day [before] ED transport), and prehospital ECG changes (OR=6.64; 95% CI, 2.31 to 19.12) were independently associated with severe ED hyperkalemia. A model incorporating these factors had good discrimination (c-statistic 0.82; 95% CI, 0.76 to 0.89) and, using a cutoff of 25% probability, correctly classified patients 89% of the time. Conclusions: Characteristics available at the time of ambulance-ED were associated with severe ED hyperkalemia. An awareness of these associations may allow health care providers to define novel care pathways to ensure timely diagnosis and management of hyperkalemia.