Cannabis use is associated with reduced access to kidney transplantation and an increased risk of acute rejection post-transplant.

BACKGROUND: The association between cannabis use and access to waitlisting, transplantation, and post-transplant outcomes remains uncertain. METHODS: Patients referred for kidney transplant (KT) to the University Health Network from January 1, 2003, to June 30, 2020, and followed until December 31, 2020, were included. Predictors of reported cannabis use were examined using a logistic regression model. The association between cannabis use and time to clearance for KT, undergoing KT, and post-transplant outcomes was evaluated using Cox proportional hazards models. RESULTS: Among 3734 patients, the prevalence of reported cannabis use was 11.8%. Cannabis use was associated with a lower likelihood of KT clearance (adjusted hazard ratio [aHR] .82 [95% confidence interval (CI): .72, .94]). Once cleared for KT, cannabis use did not predict the subsequent receipt of KT (aHR .92, [95% CI: .79, 1.08]). Among 2091 KT recipients, cannabis use was associated with a higher likelihood of biopsy-proven acute rejection (aHR 1.55, [95% CI: 1.06, 2.27]). The relative hazard of death-censored graft failure was similarly elevated (aHR 1.60 [95% CI: .95, 2.72]). Cannabis use did not predict total graft failure (aHR 1.33 [95% CI: .90, 1.96]), death with graft function (aHR 1.06 [95% CI: .59, 1.89]), or hospital readmission in the first-year post-transplant (aHR 1.26 [95% CI: .95, 1.68]). CONCLUSIONS: Cannabis users have less access to transplantation and an increased risk of acute rejection, possibly leading to more graft loss. Further studies are warranted to understand possible mechanisms for the increased risk of allograft immune injury among cannabis users.

Effectiveness of first, second, and third COVID-19 vaccine doses in solid organ transplant recipients: A population-based cohort study from Canada.

Limited data exists on the effectiveness of a third COVID-19 vaccine dose in solid organ transplant recipients. We conducted a population-based cohort study using linked healthcare databases from Ontario, Canada to answer this question. We included solid organ transplant recipients (n = 12,842) as of December 14, 2020, with follow-up until November 28, 2021. We used an extended Cox proportional hazards model with vaccination status, including BNT162b2, mRNA-1273, and ChAdOx1 vaccines, modeled as a time-dependent exposure. Individuals started in the unvaccinated category (reference) and could contribute person-time to first, second, and third doses. Over a median follow-up of 349 days, 12.7% (n = 1632) remained unvaccinated, 54.1% (n = 6953) received 3 doses, and 488 (3.8%) tested positive for SARS-CoV-2 (of which 260 [53.3%] had a clinically important outcome [i.e., hospitalization or death]). Adjusted vaccine effectiveness against infection was 31% (95% CI: 2, 51%), 46% (95% CI: 21, 63%), and 72% (95% CI: 43, 86%) for one, two, and three doses. Vaccine effectiveness against clinically important outcomes was 38% (95% CI: 4, 61%), 54% (95% CI: 23, 73%), and 67% (95% CI: 11, 87%). Vaccine effectiveness in solid organ transplant recipients is lower than the general population, however, vaccine effectiveness improved following a third dose.

Incidence, risk factors, outcomes, and clinical management of BK viremia in the modern era of kidney transplantation.

BK viremia is endemic among kidney transplant recipients (KTRs). Incidence, risk factors, outcomes, and clinical management of detectable versus high BK viremia have not been considered previously in KTR in the modern era. This observational study examined KTR transplanted between January 1, 2009 and December 31, 2016. Any BK viral load in the serum constituted detectable BK viremia and ≥103 copies/ml constituted high viremia. Among 1193 KTRs, the cumulative probability of developing detectable and high BK viremia within 2 years posttransplant were 27.8% and 19.6%, respectively. Significant risk factors for detectable BK viremia included recipient age (HR 1.02 [95% CI: 1.01, 1.03]) and donor age (HR 1.01 [95% CI: 1.00, 1.02]). Recipient age also predicted high BK viremia (HR 1.02 [95% CI: 1.01, 1.03]), whereas White race (HR 0.70 [95% CI: 0.52, 0.95]), nondepleting induction therapy (HR 0.61 [95% CI: 0.42, 0.89]), and delayed graft function (HR 0.61 [95% CI: 0.42, 0.88]) were protective. Mean estimated glomerular filtration rates were 4.28 ml/min/1.72 m2 (95% CI: 2.71, 5.84) lower with detectable BK viremia. Although low viral load was usually not acted upon at first presentation, antiproliferative dose reductions were the most common initial management. BK viremia remains a common early complication in a modern cohort of KTRs. These findings highlight the benefit of early BKV monitoring in addition to intensive clinical management. Clinical responses beyond first positive BK viremia tests, and their implications for graft outcomes, merit further investigation.

Engaging high school students about organ donation and transplantation: an evaluation of the High School Outreach Initiative (HSOI) program.

Adolescents can be influential in changing societal perceptions of organ donation and transplantation (ODT) but current studies on youth are limited. We sought to (1) assess the baseline knowledge in ODT among students in Toronto, Canada, and (2) evaluate the effectiveness of the High School Outreach Initiative (HSOI) program presentations in changing awareness and interest about ODT. Pre- and post-presentation surveys were administered to high school students about their knowledge of ODT, awareness of donor registration, importance of donation, intent to register, and willingness to talk to their families about donation. Descriptive statistics were used to characterize the students' baseline knowledge and interest. Wilcoxon and McNemar tests were used to analyze changes in perceptions before and after the presentation. A total of 449 HSOI presentations were delivered to 33,090 students at 102 high schools in the Greater Toronto Area between 2012 and 2019. Data from 3327 surveys completed by students before a presentation showed 46.5% were not knowledgeable about ODT. For the 2-year period between 2017 and 2019, 1224 matched pre- and post-presentation surveys were collected. The 49.8% of students who stated they were not knowledgeable about ODT prior to the presentation decreased to 3.8% after (p < 0.001). Those who were not willing to register decreased by half after the presentation (p < 0.001). The HSOI is an effective educational program in improving youth's attitudes and perceptions toward ODT. Further directions of the program include the expansion to other cities and the collection of demographic information of students.

Incidence of new-onset diabetes mellitus and association with mortality in childhood solid organ transplant recipients: a population-based study.

BACKGROUND: Precise estimates of the long-term risk of new-onset diabetes and its impact on mortality among transplanted children are not known. METHODS: We conducted a cohort study comparing children undergoing solid organ (kidney, heart, liver, lung and multiple organ) transplant (n = 1020) between 1991 and 2014 with healthy non-transplanted children (n = 7 134 067) using Ontario health administrative data. Outcomes included incidence of diabetes among transplanted and non-transplanted children, the relative hazard of diabetes among solid organ transplant recipients, overall and at specific intervals posttransplant, and mortality among diabetic transplant recipients. RESULTS: During 56 019 824 person-years of follow-up, the incidence rate of diabetes was 17.8 [95% confidence interval (CI) 15-21] and 2.5 (95% CI 2.5-2.5) per 1000 person-years among transplanted and non-transplanted children, respectively. The transplant cohort had a 9-fold [hazard ratio (HR) 8.9; 95% CI 7.5-10.5] higher hazard of diabetes compared with those not transplanted. Risk was highest within the first year after transplant (HR 20.7; 95% CI 15.9-27.1), and remained elevated even at 5 and 10 years of follow-up. Lung and multiple organ recipients had a 5-fold (HR 5.4; 95% CI 3.0-9.8) higher hazard of developing diabetes compared with kidney transplant recipients. Transplant recipients with diabetes had a three times higher hazard of death compared with those who did not develop diabetes (HR 3.3; 95% CI 2.3-4.8). CONCLUSIONS: The elevated risk of diabetes in transplant recipients persists even after a decade, highlighting the importance of ongoing surveillance. Diabetes after transplantation increases the risk of mortality among childhood transplant recipients.

Ethnic background is associated with no live kidney donor identified at the time of first transplant assessment-an opportunity missed? A single-center retrospective cohort study.

Patients from ethnocultural minorities have reduced access to live donor kidney transplant (LDKT). To explore early pretransplant ethnocultural disparities in LDKT readiness, and the impact of the interactions with the transplant program, we assessed if patients had a potential live donor (LD) identified at first pretransplant assessment, and if patients with no LD initially received LDKT subsequently. Single-center, retrospective cohort of adults referred for kidney transplant (KT) assessment. Multivariable logistic regression assessed the association between ethnicity and having a potential LD. Cox proportional hazard analysis assessed the association between no potential LD initially and subsequent LDKT. Of 1617 participants, 66% of Caucasians indicated having a potential LD, compared with 55% of South Asians, 44% of African Canadians, and 41% of East Asians (P < 0.001). In multivariable logistic regression analysis, the odds of having a potential LD identified was significantly lower for African, East and South Asian Canadians. No potential LD at initial KT assessment was associated with lower likelihood of LDKT subsequently (hazard ratio [HR], 0.14; [0.10-0.19]). Compared to Caucasians, African, East and South Asian and African Canadians are less likely to have a potential LD identified at first KT assessment, which predicts a lower likelihood of subsequent LDKT.

Postoperative surgical-site hemorrhage after kidney transplantation: incidence, risk factors, and outcomes.

Studies investigating the incidence, risk factors, and outcomes of surgical-site hemorrhage after kidney transplantation are limited. Patients who underwent a kidney transplant from 1 January 2000 to 30 September 2012 (followed until 31 December 2012) at Toronto General Hospital were included in this study. Postoperative surgical-site hemorrhage was defined as a drop in hemoglobin ≥20 g/l over a 24-hour period within 3 days of transplantation, followed by an ultrasound indicating a significant hematoma/collection. A total of 59 of 1203 (4.9%) kidney transplant recipients had postoperative surgical-site hemorrhage. Most cases (89.8%) occurred within 1 day after transplantation. Living donor transplants [OR 0.30 (95% CI: 0.16, 0.55)] and higher recipient BMI [OR 0.54 per 10 kg/m2 increase in BMI (95% CI: 0.30, 0.99)] were associated with a significantly lower risk of bleeding. Chronic preoperative anticoagulant usage led to an increased risk of bleeding but was not statistically significant [OR 1.75 (95% CI: 0.52, 5.88)]. Postoperative hemorrhage was associated with a higher risk of graft loss or death [HR 1.62 (95% CI: 1.01, 2.60)]. While the incidence of postoperative surgical-site hemorrhage in kidney transplantation is relatively low, it may be associated with an increased risk of graft loss or death.

Health information management for research and quality assurance: the Comprehensive Renal Transplant Research Information System.

The Kidney Transplant Program at the Toronto General Hospital uses numerous electronic health record platforms housing patient health information that is often not coded in a systematic manner to facilitate quality assurance and research. To address this, the comprehensive renal transplant research information system was conceived by a multidisciplinary healthcare team. Data analysis from comprehensive renal transplant research information system presented at programmatic retreats, scientific meetings, and peer-reviewed manuscripts contributes to quality improvement and knowledge in kidney transplantation.

Selective Elimination and Rationalization of Cell-based Assays in Deceased Donor Kidney Transplant Crossmatching.

Background: While there is increasing reliance on a negative virtual crossmatch to proceed with deceased donor kidney transplantation, a flow cytometry crossmatch (FCXM) is still usually performed after the transplant has already occurred. Our center has eliminated pretransplant physical crossmatches for most patients, and since 2018, we have eliminated the systematic performance of posttransplant FCXMs. Methods: We studied all deceased donor kidney transplants in our program between June 1, 2018, and March 31, 2021, to evaluate the impact of eliminating retrospective FCXMs on resource utilization and graft outcomes (ie, the occurrence of antibody-mediated rejection [AMR] in the first 3-mo posttransplant). Results: A total of 358 kidney transplants occurred during the study period, and approximately 70% of these transplants proceeded without the performance of any FCXM. Incidence rates of AMR were low (9.63 per 1000 person-months), which compared favorably with the incidence rate of AMR during the 3-y period preceding the policy (4.82 per 1000 person-months, P = 0.21). Conclusions: Our results suggest that moving away from retrospective FCXM and relying exclusively on the virtual crossmatch is safe and efficient for kidney allocation.

Performance measures for the evaluation of patients referred to the Toronto General Hospital's kidney transplant program.

Given the increasing number of patients with end-stage renal disease in Ontario, there is a need to improve the efficiency and effectiveness of the pretransplant evaluation, to allow for a seamless progression through the various steps in the process. Toronto General Hospital's kidney transplant program is evaluating various performance measures, specifically looking at waiting times from referral to initial evaluation and initial evaluation to final disposition, to use as metrics for monitoring program performance and stimulate quality improvement.

Older Age is Associated With Lower Utilization of Living Donor Kidney Transplant.

Introduction: Older adults (65 years or older) constitute a substantial and increasing proportion of patients with kidney failure, potentially needing kidney replacement therapy. Living donor kidney transplant (LDKT) offers superior outcomes for suitable patients of all ages. However, exploring LDKT and finding a living donor could be challenging for older adults. Here, we assessed the association between age and utilization of LDKT and assessed effect modification of key variables such as ethnicity and language. Methods: This is a retrospective cohort study of patients with kidney failure referred for kidney transplant (KT) assessment in Toronto between January 2006 and December 2013. The association between age and having a potential living donor identified was assessed using logistic regression and the association between age and the receipt of LDKT was assessed using Cox proportional hazards models. Results: Of the 1617 participants, 50% were middle-aged (45-64 years old), and 17% were ≥65 years old. In our final multivariable adjusted models, compared to young adults, middle-aged and older adults had lower odds of having a potential living donor identified (odds ratio [OR], 0.47; confidence interval [CI], [0.35-0.63]; OR, 0.30; CI, [0.20-0.43]; P < 0.001, for middle-aged and older adults, respectively), and were less likely to receive LDKT (hazard ratio [HR], 0.79; CI, [0.63-0.99]; P = 0.04; HR, 0.47; CI, [0.30-0.72]; P = 0.001, for middle-aged and older adults, respectively.). Conclusion: Age is an independent predictor of receiving LDKT. Considering that nearly 90% of patients with kidney failure in Canada are >45 years of age, these results point to important and potentially modifiable age-related barriers to LDKT.

Organ donation after cardiac death: donor and recipient outcomes after the first three years of the Ontario experience.

PURPOSE: The aim of this study was to explore donor and recipient outcomes from organ donation after cardiac death (DCD) in Ontario and to examine the impact of DCD on deceased donation rates in Ontario since its implementation. METHODS: Donor data were obtained from the Trillium Gift of Life Network (TGLN) TOTAL database from June 1, 2006 until May 31, 2009. All DCDs were tracked, including unsuccessful DCD attempts during that time. For the first 36 months after DCD implementation, all Ontario solid organ transplant programs that utilized organs from DCD provided clinical outcome data at one year. Total DCD activity until December 1, 2010 was also tracked. In addition, we compared organ donation and DCD rates across all Canadian jurisdictions and the USA. RESULTS: For the first 36 months of DCD activity in Ontario, June 1, 2006 to May 31, 2009, there were 67 successful DCDs out of 87 attempted DCDs in 18 Ontario hospitals, resulting in 128 kidney, 41 liver, and 21 lung transplants. The one-year kidney patient and death-censored allograft survivals were 96 and 97%, respectively. Mean (SD) creatinine at 12 months was 150 (108) µmol·L(-1). In 26 (20%) extended criteria donors (ECD-DCD), the one-year creatinine was 206 (158) µmol·L(-1) vs 137 (80) µmol·L(-1) in 102 standard criteria donors (SCD-DCD) (P = 0.002). The one-year liver and lung allograft survivals were 78% and 70%, respectively. Since its implementation four and a half years ago, DCD has accounted for 10.9% of deceased donor activity in Ontario. In 2009, Ontario had a record number of organ donors. Of the 221 deceased donors, 37 (17%) donors were DCD. By December 1, 2010 there were 121 DCD Ontario donors resulting in > 300 solid organ transplants and accounting for 90% of all DCD activity in the country. CONCLUSION: The rapid update of DCD in Ontario can be attributed to strong proponents in the critical care and transplantation communities with continued support from Trillium Gift of Life Network (TGLN). Ontario is the only province to demonstrate growth in deceased donor rates over the last decade (25% over the last four years), which can be attributed primarily to the success of its DCD activity.

Randomized Controlled Trial of a Computer-Based Education Program in the Home for Solid Organ Transplant Recipients: Impact on Medication Knowledge, Satisfaction, and Adherence.

BACKGROUND: De novo solid organ transplant recipients (SOTR) have a steep learning curve to acquire medication knowledge. Without adequate knowledge, SOTR are at risk of nonadherence and poor transplant outcomes. METHODS: In this nonblinded, randomized controlled trial, de novo SOTR received standard teaching with or without postdischarge computer-based education (CBE) at home. Primary outcomes were change in knowledge (quiz and recall) and satisfaction, assessed by questionnaires at baseline and 3 months. Adherence was evaluated via self-report and immunosuppressant levels. RESULTS: Two hundred forty-six patients were randomized and 209 completed the 3-month analysis. In the intervention arm, 73 (57.9%) used the CBE program. Change in knowledge quiz score did not differ between groups (4.9% vs 0.6%; P = 0.084), despite a significant increase within the intervention (72.4% vs 77.3%, P = 0.007) but not the control (76.0% vs 76.6%, P = 0.726) arms. Both groups had a significant improvement in recall (intervention, 56.7% vs 82.1%, P < 0.001; control, 51.3% vs 79.7%, P < 0.001), with similar changes in scores (25.4% vs 28.4%, P = 0.55). Change in satisfaction differed between groups (intervention, 1.2% vs control, -4.9%; P = 0.050). There was a significant decline in satisfaction within the control group (88.4% vs 83.5%, P = 0.035), whereas satisfaction was maintained with the intervention (85.6% vs 86.8%, P = 0.55). Adherence was similar in both groups. CONCLUSIONS: Knowledge improved over the study period in both groups, with no incremental benefit for the intervention. Patient satisfaction was maintained with the CBE program. More research is needed to identify barriers to uptake of CBE at home and to develop effective strategies for posttransplant education.

Kidney function before pancreas transplant alone predicts subsequent risk of end-stage renal disease.

BACKGROUND: Recipients of a pancreas transplant alone (PTA) have varying levels of kidney function at the time of transplantation, but the role of kidney function in predicting the risk of end-stage renal disease (ESRD) after PTA remains unclear. METHODS: A study was conducted on 1,135 adult recipients of a first PTA from January 1, 1994 to December 31, 2009 in the Scientific Registry of Transplant Recipients. ESRD events were derived from the United States Renal Data System. Cox proportional hazards models were fitted to determine the independent association of the estimated glomerular filtration rate (eGFR) by the Chronic Kidney Disease Epidemiology Collaboration formula before PTA and ESRD. The continuous relation between eGFR and ESRD was modeled using fractional polynomial terms. RESULTS: The cumulative probabilities of ESRD for eGFR ≥ 90, 60 to 89.9, and <60 mL/min/1.73 m(2) at 5 years were 3.5, 12.2, and 26.0%, and at 10 years were 21.8, 29.9, and 52.2%, respectively. Patients with eGFR <60 and 60 to 89.9 mL/min/1.73 m(2) were 7.74 (95% CI: 4.37, 13.74) and 3.25 (95% CI: 1.77, 5.97) times more likely to develop ESRD than patients with eGFR ≥ 90 mL/min/1.73 m(2). The fractional polynomial model showed a log-linear relation between eGFR and the hazard ratio for ESRD. The results were robust to several sensitivity analyses. CONCLUSIONS: Kidney function before PTA is a strong independent predictor of ESRD. These results may inform patient selection and the use of targeted interventions to reduce the risk of progressive kidney impairment in this patient population.

A cross-sectional study examining the functional independence of elderly individuals with a functioning kidney transplant.

BACKGROUND: Cross-sectional studies of patients dependent on dialysis show that they have a high need for help with routine daily activities. In many cases, individuals who undergo kidney transplantation have previously been treated with dialysis for a significant period of time, thus many of the characteristics may be similar. The purpose of this study was to estimate the rate of functional disability in a cross-sectional population of older patients with a functioning kidney transplant. METHODS: Kidney transplant patients, aged 65 years or more, were approached to participate. Patients were interviewed to ascertain current living situation, employment status, and 1-year fall history. Functional assessments included the Barthel Index, the Lawton-Brody Scale, the Timed Up and Go (TUG) test, and dynamometer handgrip strength. RESULTS: Eighty-two patients (71%) agreed to participate. Over half (54%) reported being disabled or requiring assistance for at least one daily-living activity, with housekeeping, grocery shopping, and laundry being the activities most commonly affected. Most patients had markedly impaired TUG and handgrip tests, and 21% recalled having fallen more than once in the past year. LIMITATIONS: We used a single-center, cross-sectional study design. CONCLUSIONS: These results demonstrate a high prevalence of functional dependence, unintentional falls, and significant morbidity associated with decreased muscle strength in the older kidney transplant population.

Organ donation and transplantation in Canada: insights from the Canadian Organ Replacement Register.

PURPOSE OF REVIEW: To provide an overview of the transplant component of the Canadian Organ Replacement Register (CORR). FINDINGS: CORR is the national registry of organ failure in Canada. It has existed in some form since 1972 and currently houses data on patients with end-stage renal disease and solid organ transplants (kidney and/or non-kidney). The transplant component of CORR receives data on a voluntary basis from individual transplant centres and organ procurement organizations across the country. Coverage for transplant procedures is comprehensive and complete. Long-term outcomes are tracked based on follow-up reports from participating transplant centres. The longitudinal nature of CORR provides an opportunity to observe the trajectory of a patient's journey with organ failure over their life span. Research studies conducted using CORR data inform both practitioners and health policy makers alike. IMPLICATIONS: The importance of registry data in monitoring and improving care for Canadian transplant candidates/recipients cannot be over-stated. This paper provides an overview of the transplant data in CORR including its history, data considerations, recent findings, new initiatives, and future directions.

BUT DE LA REVUE: Offrir un aperçu du volet « transplantation d'organes ¼ du Registre canadien des insuffisances et des transplantations d'organes (RCITO). RÉSULTATS: Le RCITO est le Registre canadien des insuffisances d'organes au Canada. Il a commencé à prendre forme en 1972, et contient à l'heure actuelle des données sur des patients atteints de néphropathie terminale et sur des transplantations (rénales ou non rénales) d'organes pleins. Le volet « transplantation d'organes ¼ du RCITO collige des données qui ont été envoyées, sur une base volontaire, par des centres de transplantation et des services d'approvisionnement en organes à travers le pays. Le Registre offre une couverture exhaustive et complète des différentes interventions de transplantation. Les résultats à long terme sont retracés à partir de rapports de rendez-vous de suivi des centres de transplantation participants. L'ampleur longitudinale du RCITO offre la possibilité d'observer le parcours, tout au long de sa vie, du patient atteint d'une insuffisance organique. Les études produites à partir des données du RCITO éclairent à la fois les praticiens et les décideurs du domaine de la santé. IMPLICATIONS: On ne peut surestimer l'importance des données du Registre lorsqu'il s'agit d'effectuer le suivi des candidats canadiens potentiels à une transplantation, ou d'améliorer les soins qui leur sont offerts. Cette revue offre un aperçu des données du RCITO qui se rapportent à la transplantation d'organes, dont : l'historique, les éléments à considérer sur les données, des résultats récents, de nouvelles initiatives et les orientations futures.

Discovering misattributed paternity in living kidney donation: prevalence, preference, and practice.

When evaluating a living kidney donor and recipient with a father-child relationship, it may be discovered that the two are not biologically related. We analyzed data from the United Network for Organ Sharing and the Canadian Organ Replacement Registry to determine how frequently this occurs. We surveyed 102 potential donors, recipients, and transplant professionals for their opinion on whether such information should be disclosed to the donor-recipient pair. We communicated with transplant professionals from 13 Canadian centers on current practices for handling this information. In the United States and Canada, the prevalence of father-child living kidney donor-recipient pairs with less than a one-haplotype human leukocyte antigen match (i.e., misattributed paternity) is between 1% and 3%, or approximately 0.25% to 0.5% of all living kidney donations. Opinions about revealing this information were variable: 23% strongly favored disclosure; whereas, 24% were strongly opposed to it. Current practices are variable; some centers disclose this information, whereas others do not. Discovering misattributed paternity in living donation is uncommon but can occur. Opinions on how to deal with this sensitive information are variable. Discussion among transplant professionals will facilitate best practices and policies. Strategies adopted by some centers can be considered.