The prevalence of postacute sequelae of coronavirus disease 2019 in solid organ transplant recipients: Evaluation of risk in the National COVID Cohort Collaborative.

Postacute sequelae after the coronavirus disease (COVID) of 2019 (PASC) is increasingly recognized, although data on solid organ transplant (SOT) recipients (SOTRs) are limited. Using the National COVID Cohort Collaborative, we performed 1:1 propensity score matching (PSM) of all adult SOTR and nonimmunosuppressed/immunocompromised (ISC) patients with acute COVID infection (August 1, 2021 to January 13, 2023) for a subsequent PASC diagnosis using International Classification of Diseases, 10th Revision, Clinical Modification codes. Multivariable logistic regression was used to examine not only the association of SOT status with PASC, but also other patient factors after stratifying by SOT status. Prior to PSM, there were 8769 SOT and 1 576 769 non-ISC patients with acute COVID infection. After PSM, 8756 SOTR and 8756 non-ISC patients were included; 2.2% of SOTR (n = 192) and 1.4% (n = 122) of non-ISC patients developed PASC (P value < .001). In the overall matched cohort, SOT was independently associated with PASC (adjusted odds ratio [aOR], 1.48; 95% confidence interval [CI], 1.09-2.01). Among SOTR, COVID infection severity (aOR, 11.6; 95% CI, 3.93-30.0 for severe vs mild disease), older age (aOR, 1.02; 95% CI, 1.01-1.03 per year), and mycophenolate mofetil use (aOR, 2.04; 95% CI, 1.38-3.05) were each independently associated with PASC. In non-ISC patients, only depression (aOR, 1.96; 95% CI, 1.24-3.07) and COVID infection severity were. In conclusion, PASC occurs more commonly in SOTR than in non-ISC patients, with differences in risk profiles based on SOT status.

Adherence to guideline-recommended care of late-onset hypertension in females versus males: A population-based cohort study.

BACKGROUND: Sex-based disparities in cardiovascular outcomes may be improved with appropriate hypertension management. OBJECTIVE: To compare the evidence-based evaluation and management of females with late-onset hypertension compared to males in the contemporary era. METHODS: Design: Retrospective population-based cohort study. SETTING: Ontario, Canada. PARTICIPANTS: Residents aged ≥66 years with newly diagnosed hypertension between January 1, 2010, and December 31, 2017. EXPOSURE: Sex (female vs. male). OUTCOMES AND MEASURES: We used Poisson and logistic regression to estimate adjusted sex-attributable differences in the performance of guideline-recommended lab investigations. We estimated adjusted differences in time to the prescription of, and type of, first antihypertensive medication prescribed between females and males, using Cox regression. RESULTS: Among 111,410 adults (mean age 73 years, 53% female, median follow-up 6.8 years), females underwent a similar number of guideline-recommended investigations (adjusted incidence rate ratio, 0.997 [95% confidence interval [CI] 0.99-1.002]) compared to males. Females were also as likely to complete all investigations (0.70% females, 0.77% males; adjusted odds ratio, 0.96 [95% CI 0.83-1.11]). Females were slightly less likely to be prescribed medication (adjusted hazard ratio [aHR] 0.98 [95% CI 0.96-0.99]) or, among those prescribed, less likely to be prescribed first-line medication (aHR, 0.995 [95% CI 0.994-0.997]). CONCLUSIONS: Compared to males, females with late-onset hypertension were equally likely to complete initial investigations with comparable prescription rates. These findings suggest that there may be no clinically meaningful sex-based differences in the initial management of late-onset hypertension to explain sex-based disparities in cardiovascular outcomes.

The Relative Risk of COVID-19 in Solid Organ Transplant Recipients Over Waves of the Pandemic.

Solid organ transplant recipients (SOTR) are at increased risk from COVID-19. Over time, the absolute risk of adverse outcomes after COVID-19 has decreased in both the non-immunosuppressed/immunocompromised (non-ISC) general population, and amongst SOTR. Using the N3C, we examined the absolute risk of mortality, major adverse renal or cardiac events, and hospitalization after COVID-19 diagnosis amongst non-ISC and SOTR populations over five waves of the pandemic (Wave 1: Ancestral COVID; Wave 2: Alpha; Wave 3: Delta; Wave 4: Omicron; Wave 5: Omicron). Within each wave, we determined the relative risk of each outcome for SOTR versus the non-ISC population based on crude event rates, and then used multivariable cox proportional hazards models and logistic regression to determine the adjusted risk of each outcome based on SOT status. Throughout the pandemic, including during the Omicron wave (Wave 5), SOTR were at greater absolute risk for each outcome than non-ISC patients (p-values all <0.001). The adjusted risk of SOT status for each outcome was relatively stable over time (aHR 1.28-1.61 for mortality; aHR 1.31-1.47 for MACE; aHR 1.72-1.90 for MARCE; aHR 1.75-2.07 for AKI; and aOR 1.53-1.81 for hospitalization). Despite a reduction in the absolute risk of COVID-19 complications, the relative risk for SOTR versus the non-ISC population has not improved.

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.

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.

Sex and organ-specific risk of major adverse renal or cardiac events in solid organ transplant recipients with COVID-19.

While older males are at the highest risk for poor coronavirus disease 2019 (COVID-19) outcomes, it is not known if this applies to the immunosuppressed recipient of a solid organ transplant (SOT), nor how the type of allograft transplanted may impact outcomes. In a cohort study of adult (>18 years) patients testing positive for COVID-19 (January 1, 2020-June 21, 2021) from 56 sites across the United States identified using the National COVID Cohort Collaborative (N3C) Enclave, we used multivariable Cox proportional hazards models to assess time to MARCE after COVID-19 diagnosis in those with and without SOT. We examined the exposure of age-stratified recipient sex overall and separately in kidney, liver, lung, and heart transplant recipients. 3996 (36.4%) SOT and 91 646 (4.8%) non-SOT patients developed MARCE. Risk of post-COVID outcomes differed by transplant allograft type with heart and kidney recipients at highest risk. Males with SOT were at increased risk of MARCE, but to a lesser degree than the non-SOT cohort (HR 0.89, 95% CI 0.81-0.98 for SOT and HR 0.61, 95% CI 0.60-0.62 for non-SOT [females vs. males]). This represents the largest COVID-19 SOT cohort to date and the first-time sex-age-stratified and allograft-specific COVID-19 outcomes have been explored in those with SOT.

The risk and consequences of breakthrough SARS-CoV-2 infection in solid organ transplant recipients relative to non-immunosuppressed controls.

Clinical outcomes in solid organ transplant (SOT) recipients with breakthrough COVID (BTCo) after two doses of mRNA vaccination compared to the non-immunocompromised/immunosuppressed (ISC) general population, are not well described. In a cohort of adult patients testing positive for COVID-19 between December 10, 2020 and April 4, 2022, we compared the cumulative incidence of BTCo in a non-ISC population to SOT recipients (overall and by organ type) using the National COVID Cohort Collaborative (N3C) including data from 36 sites across the United States. We assessed the risk of complications post-BTCo in vaccinated SOT recipients versus SOT with unconfirmed vaccination status (UVS) using multivariable Cox proportional hazards and logistic regression. BTCo occurred in 4776 vaccinated SOT recipients over a median of 149 days (IQR 99-233), with the highest cumulative incidence in heart recipients. The relative risk of BTCo was greatest in SOT recipients (relative to non-ISC) during the pre-Delta period (HR 2.35, 95% CI 1.80-3.08). The greatest relative benefit with vaccination for both non-ISC and SOT cohorts was in BTCo mortality (HR 0.37, 95% CI 0.36-0.39 for non-ISC; HR 0.67, 95% 0.57-0.78 for SOT relative to UVS). While the relative benefit of vaccine was less in SOT than non-ISC, SOT patients still exhibited significant benefit with vaccination.

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

Acute Allograft Rejection in Kidney Transplant Recipients Treated With Immune Checkpoint Inhibitors: An Educational Case Report.

Rationale: Kidney transplant (KT) recipients have an increased risk of malignancy due to chronic immunosuppression. The emerging use of immune checkpoint inhibitors (ICIs) has been a promising development for the treatment of malignancy, but their use adds to the complexity of immunosuppression management for KT recipients. This case report describes 2 cases of acute rejection in KT recipients following ICI initiation and discusses the balance of malignancy treatment with adequate immunosuppression. Presenting Concerns of Patients: The first patient is a 44-year-old male KT recipient with a diagnosis of metastatic renal cell carcinoma presenting with acute kidney injury 6 days following initiation of an ICI. The second patient is a 73-year-old male KT recipient with a diagnosis of squamous cell carcinoma presenting with acute kidney injury 2 weeks following initiation of an ICI. Diagnoses: Both patients were diagnosed with acute rejection in the setting of reduced immunosuppression and initiation of an ICI. Interventions: Both cases received an increased dose of steroid without improvement of graft function. The first patient subsequently underwent a delayed graft nephrectomy due to complications of acute rejection, whereas the second patient did not undergo nephrectomy. Outcomes: The first patient experienced complications including perioperative bleeding requiring multiple operations, but ultimately stabilized on hemodialysis and showed a durable response to ICI. The second patient remained dialysis-dependent post-ICI treatment and was readmitted with allograft complications leading to his eventual death. Teaching Points: This study underscores the complexity of managing KT recipients diagnosed with malignancy and receiving ICIs. The balance between immunosuppression reduction to treat malignancy and preventing allograft rejection presents a significant challenge. Key considerations include the risk of acute allograft rejection and patient-centered decision-making. These cases highlight the need for further research to develop evidence-based guidelines for managing this patient population. In addition, the patient perspective in this study highlights the importance of careful risk-benefit analysis and the impact of treatment decisions on patient-focused outcomes.

Contexte: Les receveurs d'une greffe rénale (RGR) présentent un risque accru de cancer en raison de l'immunosuppression chronique. L'utilisation émergente des inhibiteurs du point de contrôle immunitaire (IPCI) s'est avérée un développement prometteur pour traiter les cancers, mais elle ajoute à la complexité de la gestion de l'immunosuppression chez les RGR. Cette étude décrit deux cas de rejet aigu chez des RGR après l'initiation des IPCI et discute du difficile équilibre entre le traitement du cancer et une immunosuppression adéquate. Présentation des cas: Le premier patient est un homme de 44 ans ayant reçu un diagnostic de carcinome à cellules rénales métastatique qui a présenté une insuffisance rénale aiguë six jours après l'initiation des IPCI. Le second patient est un homme de 73 ans ayant reçu un diagnostic de carcinome épidermoïde qui a présenté une insuffisance rénale aiguë deux semaines après l'initiation des IPCI. Diagnostic: Dans les deux cas, le rejet aigu a été diagnostiqué à la suite de la réduction de l'immunosuppression et de l'initiation des IPCI. Intervention: Les deux patients ont reçu une dose plus élevée de stéroïdes sans amélioration de la fonction du greffon. Le premier patient a subi une néphrectomie retardée du greffon en raison de complications de rejet aigu, ce qui n'a pas été le second patient. Résultats: Le premier patient a subi des complications, notamment des saignements périopératoires qui ont nécessité de multiples opérations, mais s'est finalement stabilisé avec l'hémodialyse et a montré une réponse durable aux IPCI. Le second patient est demeuré sous dialyse après le traitement aux IPCI et a été réadmis avec des complications de l'allogreffe qui ont entraîné son décès. Enseignements tirés: Cette étude souligne la complexité de la prise en charge des RGR qui reçoivent un diagnostic de tumeur maligne et des traitements par IPCI. L'équilibre entre la réduction de l'immunosuppression pour traiter le cancer et la prévention du rejet de l'allogreffe constitue un important défi. Le risque de rejet aigu de l'allogreffe et la prise de décision centrée sur le patient sont des éléments clés à prendre en compte. Ces deux cas soulignent la nécessité de poursuivre les recherches afin d'élaborer des lignes directrices fondées sur des données probantes pour la gestion de cette population de patients. De plus, le point de vue du patient dans cette étude met en évidence l'importance d'analyser rigoureusement le rapport risques-bénéfices et l'impact des décisions de traitement sur les résultats axés sur le patient.

Exploring Potential Gender-Based Disparities in Referral for Transplant, Activation on the Waitlist and Kidney Transplantation in a Canadian Cohort.

Introduction: In the United States, women are less likely to be referred, activated on the waitlist, or undergo kidney transplant (KT) than men; contemporary Canadian data regarding access to transplant for women are lacking. Methods: Among patients initiating dialysis in Nova Scotia (NS), Canada from 2010 to 2020, we examined the association of candidate gender with overall access to KT, including the following: (i) odds of transplant referral within 1 year of dialysis initiation, (ii) odds of activation on the transplant waitlist (if referred), and (iii) time-to-transplantation (if activated) using logistic regression or Cox proportional hazards models as appropriate. Results: Among 749 patients deemed potentially eligible for transplant, women had lower transplant rates than men (adjusted hazard ratio [aHR]: 0.53, 95% confidence interval [CI]: 0.36-0.78); this was amplified among patients aged >60 years (aHR: 0.25, 95% CI: 0.09-0.69). Compared with men, women had a lower adjusted odds of transplant referral (adjusted odds ratio [aOR]: 0.57, 95% CI: 0.35-0.93) by 1 year after dialysis initiation. Among those referred, women had lower odds of waitlist activation than men (aOR: 0.58, 95% CI: 0.30-1.11); and among those activated, women had lower hazard of KT (aHR: 0.74, 95% CI: 0.51-1.09), though these differences were not statistically significant. Women in NS experience lower overall access to transplant, including less referral, activation and KT compared with men. Conclusion: Gender-based barriers to any of (or in this case each of) referral, activation, or transplantation result in inequities in access; identification of disparities at these critical decision points is an important first step toward ensuring equal access for all.

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.

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.

Systematic Review of Women Leading and Participating in Nephrology Randomized Clinical Trials.

Introduction: Women are underrepresented in the leadership of and participation in randomized controlled trials (RCTs). We conducted a bibliometric review of nephrology RCTs to examine trial leadership by women and participation of women in nephrology RCTs. Methods: A bibliometric review of RCTs published in top medical, surgical, or nephrology journals was conducted using MEDLINE and EMBASE from January 2011 to December 2021. Leadership by women as corresponding authors, women trial participation, and trial characteristics were examined with duplicate independent data extraction. Logistic regression was used to examine associations between trial characteristics and women leadership and trial participation. Results: A total of 1770 studies were screened and 395 RCTs met eligibility criteria. The number (%) of women in corresponding, first, and last authorship positions were as follows: 89 (22%), 109 (28%), and 74 (19%), respectively, without change over time (P = 0.94). The median percentage (interquartile range [IQR]) of women trial participants was 39.0% (13.5%) with no difference between women or men lead authors (P = 0.15). Men lead authors were statistically less likely to enroll women in RCTs. Women lead authors were less likely to be funded by industry (odds ratio [OR]: 0.30; 95% confidence interval [CI]: 0.14-0.63; P = 0.002) or lead international trials (OR: 0.11; 95% CI: 0.01-0.83; P = 0.03). Trials with sex-specific eligibility criteria were more likely to have women leaders (OR: 2.56; 95% CI: 1.19-5.49; P = 0.02) than those without. Discussion: Gender inequalities in RCT leadership and RCT participation exist in nephrology and did not improve over time. Strategies to improve inequalities need to be implemented and evaluated.

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.