Effect of a Novel Multicomponent Intervention to Improve Patient Access to Kidney Transplant and Living Kidney Donation: The EnAKT LKD Cluster Randomized Clinical Trial.

Importance: Patients with advanced chronic kidney disease (CKD) have the best chance for a longer and healthier life if they receive a kidney transplant. However, many barriers prevent patients from receiving a transplant. Objectives: To evaluate the effect of a multicomponent intervention designed to target several barriers that prevent eligible patients from completing key steps toward receiving a kidney transplant. Design, Setting, and Participants: This pragmatic, 2-arm, parallel-group, open-label, registry-based, superiority, cluster randomized clinical trial included all 26 CKD programs in Ontario, Canada, from November 1, 2017, to December 31, 2021. These programs provide care for patients with advanced CKD (patients approaching the need for dialysis or receiving maintenance dialysis). Interventions: Using stratified, covariate-constrained randomization, allocation of the CKD programs at a 1:1 ratio was used to compare the multicomponent intervention vs usual care for 4.2 years. The intervention had 4 main components, (1) administrative support to establish local quality improvement teams; (2) transplant educational resources; (3) an initiative for transplant recipients and living donors to share stories and experiences; and (4) program-level performance reports and oversight by administrative leaders. Main Outcomes and Measures: The primary outcome was the rate of steps completed toward receiving a kidney transplant. Each patient could complete up to 4 steps: step 1, referred to a transplant center for evaluation; step 2, had a potential living donor contact a transplant center for evaluation; step 3, added to the deceased donor waitlist; and step 4, received a transplant from a living or deceased donor. Results: The 26 CKD programs (13 intervention, 13 usual care) during the trial period included 20 375 potentially transplant-eligible patients with advanced CKD (intervention group [n = 9780 patients], usual-care group [n = 10 595 patients]). Despite evidence of intervention uptake, the step completion rate did not significantly differ between the intervention vs usual-care groups: 5334 vs 5638 steps; 24.8 vs 24.1 steps per 100 patient-years; adjusted hazard ratio, 1.00 (95% CI, 0.87-1.15). Conclusions and Relevance: This novel multicomponent intervention did not significantly increase the rate of completed steps toward receiving a kidney transplant. Improving access to transplantation remains a global priority that requires substantial effort. Trial Registration: ClinicalTrials.gov Identifier: NCT03329521.

Enhance Access to Kidney Transplantation and Living Kidney Donation (EnAKT LKD): Statistical Analysis Plan of a Registry-Based, Cluster-Randomized Clinical Trial.

Background: Enhance Access to Kidney Transplantation and Living Kidney Donation (EnAKT LKD) is a quality improvement intervention designed to enhance access to kidney transplantation and living kidney donation. We conducted a cluster-randomized clinical trial to evaluate the effect of the intervention versus usual care on completing key steps toward receiving a kidney transplant. Objective: To prespecify the statistical analysis plan for the EnAKT LKD trial. Design: The EnAKT LKD trial is a pragmatic, 2-arm, parallel-group, registry-based, open-label, cluster-randomized, superiority, clinical trial. Randomization was performed at the level of the chronic kidney disease (CKD) programs (the "clusters"). Setting: Twenty-six CKD programs in Ontario, Canada. Participants: More than 10 000 patients with advanced CKD (ie, patients approaching the need for dialysis or receiving maintenance dialysis) with no recorded contraindication to receiving a kidney transplant. Methods: The trial data (including patient characteristics and outcomes) will be obtained from linked administrative health care databases (the "registry"). Stratified covariate-constrained randomization was used to allocate the 26 CKD programs (1:1) to provide the intervention or usual care from November 1, 2017, to December 31, 2021 (4.17 years). CKD programs in the intervention arm received the following: (1) support for local quality improvement teams and administrative needs; (2) tailored education and resources for staff, patients, and living kidney donor candidates; (3) support from kidney transplant recipients and living kidney donors; and (4) program-level performance reports and oversight by program leaders. Outcomes: The primary outcome is completing key steps toward receiving a kidney transplant, where up to 4 unique steps per patient will be considered: (1) patient referred to a transplant center for evaluation, (2) a potential living kidney donor begins their evaluation at a transplant center to donate a kidney to the patient, (3) patient added to the deceased donor transplant waitlist, and (4) patient receives a kidney transplant from a living or deceased donor. Analysis plan: Using an intent-to-treat approach, the primary outcome will be analyzed using a patient-level constrained multistate model adjusting for the clustering in CKD programs. Trial Status: The EnAKT LKD trial period is November 1, 2017, to December 31, 2021. We expect to analyze and report the results once the data for the trial period is available in linked administrative health care databases. Trial Registration: The EnAKT LKD trial is registered with the U.S. National Institute of Health at clincaltrials.gov (NCT03329521 available at https://clinicaltrials.gov/ct2/show/NCT03329521). Statistical Analytic Plan: Version 1.0 August 26, 2022.

Contexte: EnAKT LKD est une intervention d'amélioration de la qualité visant à améliorer l'accès à la transplantation rénale et au don vivant de rein. Nous avons mené un essai clinique randomisé par grappes afin d'évaluer l'effet de l'intervention, par rapport aux soins habituels, sur le taux d'étapes clés réalisées dans le processus de réception d'une greffe de rein. Objectif: Exposer les grandes lignes du plan d'analyse statistique de l'essai EAKT LKD. Conception: EAKT LKD est un essai clinique pragmatique ouvert, à deux bras, en groupes parallèles, basé sur un registre, et randomisé en grappes. La randomisation a été réalisée au niveau des programmes d'insuffisance rénale chronique (IRC) (les « grappes ¼). Cadre: 26 programmes d'IRC en Ontario (Canada). Sujets: Plus de 10 000 patients atteints d'IRC de stade avancé (des patients approchant le besoin de dialyse ou recevant une hémodialyse d'entretien) sans contre-indication documentée à la greffe rénale. Méthodologie: Les données de l'essai (y compris les caractéristiques et les résultats des patients) seront obtenues à partir de bases de données administratives en santé (le « registre ¼). La randomisation stratifiée avec contraintes de covariables a servi à répartir les 26 programmes d'IRC (1:1) selon qu'ils allaient fournir l'intervention ou les soins habituels entre le 1er novembre 2017 et le 31 décembre 2021 (4,17 ans). Les programmes d'IRC du bras d'intervention ont eu droit au soutien suivant: (1) des équipes locales d'amélioration de la qualité et du soutien administratif; (2) de l'information et des ressources sur mesure pour le personnel, les patients et les donneurs vivants; (3) du soutien de la part de receveurs et de donneurs vivants; et (4) des rapports sur le rendement au niveau du programme et une surveillance assurée par les chefs de programme. Résultats: Le principal critère d'évaluation est le taux d'étapes clés accomplies vers la réception d'une greffe de rein, où jusqu'à quatre étapes uniques par patient seront comptabilisées: (1) le patient est aiguillé vers un centre de transplantation pour évaluation; (2) un possible donneur vivant de rein contacte un centre de transplantation pour un receveur en particulier et amorce son évaluation; (3) le patient est ajouté à la liste d'attente pour une transplantation d'un donneur décédé, et (4) le patient reçoit une greffe de rein d'un donneur vivant ou décédé. Plan d'analyse: Selon une approche fondée sur l'intention de traiter, le critère d'évaluation principal sera analysé au niveau du patient en utilisant un modèle multiétats contraint, corrigé dans les programmes d'IRC en fonction du regroupement. Statut de l'essai: L'essai EnAKT LKD s'est tenu du 1er novembre 2017 au 31 décembre 2021. Nous analyserons les résultats et en rendrons compte dès que les données seront disponibles dans les bases de données administratives couplées du système de santé.

Post-transplant outcomes in recipients of living donor kidneys and intended recipients of living donor kidneys.

BACKGROUND: Long-term kidney transplant survival at the population level is consistently favorable, but this survival varies widely at an individual level due to both recipient and donor factors. The distinct contribution of recipient and donor factors to individual post kidney transplant outcome remains unclear. Comparing outcomes in deceased donor (DD) recipients with potential but non-actualized living donors (DD1) to those recipients with actualized living donors (LD), and to DD recipients without potential living donors (DD0) may provide transplant candidates with more information about their own post-transplant prognosis. METHODS: We conducted an observational retrospective cohort study of kidney transplant candidates presenting to our centre for evaluation between 01/01/06 and 31/12/18, and who also received a transplant during that time. Patients were followed to 31/08/2019. Candidates were classified as DD0, DD1, or LD based on whether they had an identified living donor at the time of initial pre-transplant assessment, and if the donor actualized or not. Primary outcome was 5-year death-censored graft survival, adjusted for common pre- and post-transplant donor and recipient risk factors. Secondary outcomes analyzed included patient survival and graft function. RESULTS: There were 453 kidney transplant recipients (LD = 136, DD1 = 83, DD0 = 234) who received a transplant during the study period. DD0 and DD1 did not differ in key donor organ characteristics. The 5-year death censored graft survival of DD1 was similar to LD (p = 0.19). DD0 graft survival was inferior to LD (p = 0.005), but also trended inferior to DD1 (p = 0.052). By multivariate Cox regression analysis, LD demonstrated similar 5-year graft survival to DD1 (HR for graft loss 0.8 [95% CI 0.25-2.6], p = 0.72) but LD graft survival was superior to DD0 (HR 0.34 [0.16-0.72], p = 0.005). The 5-year patient survival in DD1 was similar to LD (p = 0.26) but was superior to DD0 (p = 0.01). CONCLUSIONS: DD recipients with potential but non-actualized living donors exhibit similar mid-term graft and patient survival compared to LD recipients. Having an identified living donor at the time of pre-transplant assessment portends a favorable prognosis for the recipient.

Retrospective Analysis of Tacrolimus Intrapatient Variability as a Measure of Medication Adherence.

BACKGROUND: Increased intrapatient variability (IPV) in tacrolimus levels is associated with graft rejection, de novo donor-specific antibodies, and graft loss. Medication nonadherence may be a significant contributor to high IPV. OBJECTIVE: The objective of this study is to determine the utility of tacrolimus IPV in detecting nonadherence by examining the relationship between self-reported adherence and tacrolimus coefficient of variability (COV), a measure of IPV. DESIGN: Retrospective cohort study. SETTING: St. Michael's Hospital, Toronto, Ontario. PATIENTS: All patients who were at least 1-year post-kidney transplant as of March 31, 2019, prescribed tacrolimus as an immunosuppressant and had a self-reported adherence status. Patients were excluded from the primary analysis of examining the correlation between COV and self-reported adherence if they lacked a calculatable COV. MEASUREMENTS: Self-reported adherence, COV, demographic data, transplant, and medication history. METHODS: A modified Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS) administered by healthcare professionals to assess self-reported adherence was used. The COV of tacrolimus trough levels was calculated and its correlation to BAASIS response was noted. The median COV was used as a cutoff to examine the characteristics of patients deemed "high COV" and "low COV." RESULTS: A total of 591 patients fit the initial criteria; however, only 525 had a recent calculatable COV. Overall, 92.38% of the population were adherent by self-report. Primary analysis identified a COV of 25.2% and 29.6% in self-reported adherent and nonadherent patients, respectively, though the result was not significant (P = .2). Secondary analyses showed a significant correlation between younger age at transplant and at the time of adherence self-reporting with nonadherence (P = .01). In addition, there was a strong correlation between those nonadherent with routine post-transplant blood work and younger age (P < .01). LIMITATIONS: The limitations included modified nonvalidated BAASIS questionnaire, social desirability bias, BAASIS only administered in English, and patients with graft failure not active in clinic not being captured. CONCLUSIONS: The COV should not be used as the sole method for determining medication adherence. However, COV may have some utility in capturing individuals who are not adherent to their blood work or patients who are having a poor response to tacrolimus and should be switched to another medication.

CONTEXTE: Une plus grande variabilité intra-individuelle des taux de tacrolimus est associée au rejet de la greffe, aux anticorps spécifiques au donneur de novo et à la perte du greffon. La non-observance du traitement médicamenteux pourrait être un facteur important de cette variabilité élevée. OBJECTIF: L'objectif de cette étude était d'évaluer la pertinence de la variabilité intra-individuelle des taux de tacrolimus pour la détection de la non-observance en examinant la relation entre l'observance autodéclarée et le coefficient de variabilité (CoV) du tacrolimus, une mesure de la variabilité intra-individuelle. TYPE D'ÉTUDE: Étude de cohorte rétrospective. CADRE: L'hôpital St Michael's de Toronto (Ontario). SUJETS: Tous les patients qui, au 31 mars 2019, avaient subi une transplantation depuis au moins un an, à qui on avait prescrit du tacrolimus comme immunosuppresseur et qui déclaraient adhérer à leur traitement. Les patients qui ne disposaient pas d'un CoV calculable ont été exclus de l'analyse principale examinant la corrélation entre le CoV et l'observance autodéclarée. MESURES: L'observance autodéclarée, le CoV, les données démographiques, ainsi que les antécédents de transplantation et pharmaceutiques des patients. MÉTHODOLOGIE: Une version modifiée du questionnaire BAASIS (Basel Assessment of Adherence to Immunosuppressive Medications Scale) administrée par les professionnels de la santé a été employée pour évaluer l'observance autodéclarée. Le CoV des concentrations minimales de tacrolimus a été calculé et sa corrélation avec les réponses au questionnaire BAASIS a été notée. Le CoV médian a été employé comme mesure limite pour examiner les caractéristiques des patients réputés avoir un « CoV élevé ¼ ou un « CoV faible ¼. RÉSULTATS: Au total, 591 patients satisfaisaient aux critères initiaux, mais seulement 525 disposaient d'une mesure récente et calculable du CoV. Dans l'ensemble, 92,38 % de la population étudiée déclarait adhérer au traitement. L'analyse primaire a permis d'établir le CoV à 25,2 % chez les patients adhérents et à 29,6 % chez les patients non-adhérents; bien que les résultats n'aient pas été jugés significatifs (p = 0,2). Les analyses secondaires ont montré une corrélation significative entre la non-observance autodéclarée au traitement et le fait d'être plus jeune au moment de la transplantation (p = 0,01). On a en outre observé une forte corrélation entre la non-observance des bilans sanguins habituels post-transplantation et un plus jeune âge (p < 0,01). LIMITES: La version modifiée du questionnaire BAASIS n'a pas été validée, l'étude comporte de possibles biais de désirabilité sociale, le questionnaire BAASIS n'a été passé qu'en anglais et les patients avec échec de la greffe qui étaient inactifs en clinique n'ont pu être saisis. CONCLUSION: Le coefficient de variabilité ne devrait pas être le seul élément à considérer pour déterminer l'adhérence au traitement. Ce coefficient peut cependant avoir une certaine utilité pour repérer les patients qui ne font pas leurs bilans sanguins ou les patients qui répondent peu au tacrolimus et qui devraient passer à un autre médicament.

A Quality Improvement Intervention to Enhance Access to Kidney Transplantation and Living Kidney Donation (EnAKT LKD) in Patients With Chronic Kidney Disease: Clinical Research Protocol of a Cluster-Randomized Clinical Trial.

BACKGROUND: Many patients with kidney failure will live longer and healthier lives if they receive a kidney transplant rather than dialysis. However, multiple barriers prevent patients from accessing this treatment option. OBJECTIVE: To determine if a quality improvement intervention provided in chronic kidney disease (CKD) programs (vs. usual care) enables more patients with no recorded contraindications to kidney transplant to complete more steps toward receiving a kidney transplant. DESIGN: This protocol describes a pragmatic 2-arm, parallel-group, open-label, registry-based, cluster-randomized clinical trial-the Enhance Access to Kidney Transplantation and Living Kidney Donation (EnAKT LKD) trial. SETTING: All 26 CKD programs in Ontario, Canada, with a trial start date of November 1, 2017. The original end date of March 31, 2021 (3.4 years) has been extended to December 31, 2021 (4.1 years) due to the COVID-19 pandemic. PARTICIPANTS: During the trial, the 26 CKD programs are expected to care for more than 10 000 adult patients with CKD (including patients approaching the need for dialysis and patients receiving dialysis) with no recorded contraindications to a kidney transplant. INTERVENTION: Programs were randomly allocated to provide a quality improvement intervention or usual care. The intervention has 4 main components: (1) local quality improvement teams and administrative support; (2) tailored education and resources for staff, patients, and living kidney donor candidates; (3) support from kidney transplant recipients and living kidney donors; and (4) program-level performance reports and oversight by program leaders. PRIMARY OUTCOME: The primary outcome is the number of key steps completed toward receiving a kidney transplant analyzed at the cluster level (CKD program). The following 4 unique steps per patient will be counted: (1) patient referred to a transplant center for evaluation, (2) at least one living kidney donor candidate contacts a transplant center for an intended recipient and completes a health history questionnaire to begin their evaluation, (3) patient added to the deceased donor transplant wait list, and (4) patient receives a kidney transplant from a living or deceased donor. PLANNED PRIMARY ANALYSIS: Study data will be obtained from Ontario's linked administrative healthcare databases. An intent-to-treat analysis will be conducted comparing the primary outcome between randomized groups using a 2-stage approach. First stage: residuals are obtained from fitting a regression model to individual-level variables ignoring intervention and clustering effects. Second stage: residuals from the first stage are aggregated at the cluster level as the outcome. LIMITATIONS: It may not be possible to isolate independent effects of each intervention component, the usual care group could adopt intervention components leading to contamination bias, and the relatively small number of clusters could mean the 2 arms are not balanced on all baseline prognostic factors. CONCLUSIONS: The EnAKT LKD trial will provide high-quality evidence on whether a multi-component quality improvement intervention helps patients complete more steps toward receiving a kidney transplant. TRIAL REGISTRATION: Clinicaltrials.gov; identifier: NCT03329521.

CONTEXTE: Plusieurs patients atteints d'insuffisance rénale vivront plus longtemps et en meilleure santé s'ils reçoivent une greffe de rein plutôt que des traitements de dialyze. De nombreux obstacles empêchent cependant les patients d'accéder à la transplantation. OBJECTIF: Déterminer si une intervention visant l'amélioration de la qualité menée dans les programs d'insuffisance rénale chronique (IRC) permettrait à davantage de patients sans contre-indications à une greffe d'aller plus loin (comparativement aux soins habituels) dans le processus menant à la transplantation. TYPE D'ÉTUDE: Ce protocole décrit un essai clinique pragmatique ouvert, à deux bras, en groupes parallèles, à répartition aléatoire en grappes et fondé sur un registre ­ l'essai Enhance Access to Kidney Transplantation and Living Kidney Donation (EnAKT LKD). CADRE: Les 26 programs d'IRC de l'Ontario (Canada). L'essai a débuté le 1er novembre 2017 et devait initialement se terminer le 31 mars 2021 (3,4 ans); cette date a été reportée au 31 décembre 2021 (4,1 ans) en raison de la pandémie de COVID-19. SUJETS: Au cours de l'essai, on estime que les 26 programs d'IRC prendront en charge plus de 10 000 adultes atteints d'IRC (y compris des patients approchant le besoin de dialyze et des patients dialysés) sans contre-indications à une greffe. INTERVENTIONS: Les programs ont été répartis aléatoirement pour intégrer une intervention d'amélioration de la qualité ou pour prodiguer les soins habituels. L'intervention consiste en quatre composantes principales: (1) des équipes locales d'amélioration de la qualité et de soutien administratif; (2) de l'information et des ressources sur mesure pour le personnel, les patients et les donneurs vivants; (3) du soutien pour les receveurs et les donneurs vivants; et (4) des rapports sur le rendement au niveau du program et une surveillance assurée par les chefs de program. PRINCIPAUX RÉSULTATS: Le principal critère d'évaluation est le nombre d'étapes clés complétées en vue de la réception d'une greffe de rein tel qu'analysé au niveau de la grappe (program d'IRC). Pour chaque patient, quatre étapes spécifiques seront comptabilisées: (I) le patient est aiguillé vers un center de transplantation pour évaluation; (II) au moins un donneur vivant de rein contacte un center de transplantation pour un receveur en particulier et amorce son évaluation en remplissant un questionnaire sur ses antécédents médicaux; (III) le patient est ajouté à la liste d'attente pour une transplantation d'un donneur décédé, et (IV) le patient reçoit une greffe de rein d'un donneur vivant ou décédé. PRINCIPALE ANALYZE ENVISAGÉE: Les données sont tirées des bases de données administratives du système de santé ontarien. Une analyze en intention de traiter sera effectuée en comparant le principal critère d'évaluation entre les groupes répartis aléatoirement à l'aide d'une approche en deux étapes. Première étape: obtention de valeurs résiduelles en adaptant un modèle de régression aux variables de niveau individuel et en ignorant les effets de l'intervention et du regroupement. Deuxième étape: les valeurs résiduelles de la première étape agrégées au niveau du groupe constitueront le résultat. LIMITES: Il pourrait ne pas être possible d'isoler les effets indépendants de chaque composante de l'intervention. L'équipe prodiguant les soins habituels pourrait adopter des composantes de l'intervention menant à un biais de contamination. Le nombre relativement faible de groupes pourrait signifier que les deux bras ne sont pas équilibrés sur tous les facteurs pronostiques de base. CONCLUSION: L'essai EnAKT LKD fournira des données de haute qualité sur la question de savoir si une intervention à composantes multiples visant l'amélioration de la qualité aide effectivement les patients à franchir davantage d'étapes vers une transplantation rénale.

The First North American Experience Using Glycosorb Immunoadsorption Columns for Blood Group-Incompatible Kidney Transplantation.

BACKGROUND: Blood group incompatibility (ABOi) is the most common barrier to living donor kidney transplantation. Options for such recipients include kidney paired donation (KPD) or desensitization methodology to reduce blood antibody response. OBJECTIVE: The objective of this study is to report on the first North America experience in ABOi living donor kidney transplantation using Glycosorb ABO immunoadsorption columns. DESIGN: Retrospective observational cohort study. SETTING: Renal transplant program at St. Michael's Hospital, Unity Health Toronto, University of Toronto. PATIENTS: Twenty-six ABOi living donor transplants from August 2011 through February 2020 were undertaken at our center. MEASUREMENTS: Renal allograft and patient survival postdesensitization for ABOi living donor transplants and isohemagglutinin titer reduction. METHODS: Preoperative immunosuppressive regimen consisted of a single dose of Rituximab 375 mg/m2 IV on day -28; tacrolimus, mycophenolic acid, and prednisone to start on day -7. Immunoadsorption treatments with Glycosorb A or B columns were performed on day -7 through day -1 based on anti-A or anti-B titers on Spectra Optia Apheresis System. Immunosuppression included basiliximab, solumedrol followed by oral prednisone, once-daily tacrolimus, and mycophenolic acid. The mean follow-up was 53 months (3-96 months). RESULTS: A total of 26 individuals underwent an attempt at desensitization of whom 24 patients underwent immediate transplant. One patient had a rebound in titers and subsequently was transplanted from a blood group compatible living donor. A second patient had an unrelated medical issue and desensitization was discontinued. Five-year patient survival was 96% and death censored allograft survival was 92%. Posttransplant anti-A or anti-B titers were monitored daily for the first 7 days posttransplant and every 2 days from days 7 to 14. There were no acute rejections seen in this cohort of transplant recipients. LIMITATIONS: As our protocol was first initiated as proof of concept, a few recipients had low initial isohemagglutinin titers. This may have contributed to improved clinical outcomes. CONCLUSIONS: ABO column immunoadsorption with specific columns is a safe and effective method for ABOi living donor kidney transplantation, and an option when KPD is less than ideal.Trial not registered as this was a retrospective cohort review.

CONTEXTE: L'incompatibilité du système ABO (ABOi) est l'obstacle le plus fréquent à la transplantation d'un rein provenant d'un donneur vivant. Un don croisé ou une désensibilisation visant à atténuer la réponse immunitaire constituent les seules options pour les receveurs de ce type de greffe. OBJECTIF: Faire état de la première expérience nord-américaine d'utilisation des colonnes d'immunoadsorption Glycosorb ABO pour la transplantation d'un rein ABOi provenant d'un donneur vivant. TYPE D'ÉTUDE: Étude de cohorte observationnelle rétrospective. CADRE: Le programme de transplantation rénale du centre hospitalier universitaire St Michael's de l'Unity Health Toronto. SUJETS: L'étude porte sur les 26 transplantations de reins ABOi provenant de donneurs vivants pratiquées à notre centre entre août 2011 et février 2020. MESURES: La survie du patient et de l'allogreffe après une désensibilisation en vue de la transplantation d'un rein ABOi provenant d'un donneur vivant, ainsi que la réduction du titre d'isohémagglutinine. MÉTHODOLOGIE: Le traitement préopératoire immunosuppressif consistait en une dose unique de 375 mg/m2 de Rituximab par voie intraveineuse (IV) au jour -28; et l'administration de tacrolimus, d'acide mycophénolique et de prednisone à partir du jour -7. Les traitements d'immunoadsorption avec les colonnes Glycosorb A ou B ont été effectués du jour -7 au jour -1 en fonction des titres anti-A ou anti-B obtenus avec le système d'apharèse Spectra Optia. Le traitement immunosuppressif était constitué de basiliximab, de solumédrol suivi de prednisone par voie orale, et d'une dose quotidienne de tacrolimus et d'acide mycophénolique. Le suivi s'est étalé sur une moyenne de 53 mois (3 à 96 mois). RÉSULTATS: En tout, 26 patients avaient tenté une désensibilisation, desquels 24 ont immédiatement subi une transplantation. Un rebond des titres a été observé chez un patient, lequel a par la suite été transplanté avec un organe provenant d'un donneur de groupe sanguin compatible. La désensibilisation a dû être interrompue chez un autre patient en raison d'un problème médical non relié. Cinq ans après la greffe, 96% des patients et 92% des allogreffes avaient survécu. Les titres d'anti-A et d'anti-B post-transplantation avaient été mesurés quotidiennement pour les sept premiers jours suivant l'intervention, puis tous les deux jours entre le jour 7 et le jour 14. Aucun rejet aigu n'est survenu dans la cohorte étudiée. LIMITES: Notre protocole ayant d'abord été utilisé comme preuve de concept, certains patients présentaient de faibles titres initiaux d'isohémagglutinine, ce qui pourrait avoir contribué à l'amélioration des résultats cliniques. CONCLUSIONS: L'immunoadsorption sur colonne ABO avec colonnes spécifiques s'avère une méthode sûre et efficace pour la transplantation d'un rein ABOi provenant d'un donneur vivant, et constitue une option valable lorsque le don croisé n'est pas idéal.Essai non enregistré puisqu'il s'agit d'une étude de cohorte rétrospective.

COVID-19 Outbreak in an Urban Hemodialysis Unit.

RATIONALE & OBJECTIVE: Hemodialysis patients are at increased risk for coronavirus disease 2019 (COVID-19) transmission due in part to difficulty maintaining physical distancing. Our hemodialysis unit experienced a COVID-19 outbreak despite following symptom-based screening guidelines. We describe the course of the COVID-19 outbreak and the infection control measures taken for mitigation. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 237 maintenance hemodialysis patients and 93 hemodialysis staff at a single hemodialysis center in Toronto, Canada. EXPOSURE: Universal screening of patients and staff for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). OUTCOMES: The primary outcome was detection of SARS-CoV-2 in nasopharyngeal samples from patients and staff using reverse transcriptase-polymerase chain reaction (RT-PCR). ANALYTICAL APPROACH: Descriptive statistics were used for clinical characteristics and the primary outcome. RESULTS: 11 of 237 (4.6%) hemodialysis patients and 11 of 93 (12%) staff members had a positive RT-PCR test result for SARS-CoV-2. Among individuals testing positive, 12 of 22 (55%) were asymptomatic at time of testing and 7 of 22 (32%) were asymptomatic for the duration of follow-up. One patient was hospitalized at the time of SARS-CoV-2 infection and 4 additional patients with positive test results were subsequently hospitalized. 2 (18%) patients required admission to the intensive care unit. After 30 days' follow-up, no patients had died or required mechanical ventilation. No hemodialysis staff required hospitalization. Universal droplet and contact precautions were implemented during the outbreak. Hemodialysis staff with SARS-CoV-2 infection were placed on home quarantine regardless of symptom status. Patients with SARS-CoV-2 infection, including asymptomatic individuals, were treated with droplet and contact precautions until confirmation of negative SARS-CoV-2 RT-PCR test results. Analysis of the outbreak identified 2 index cases with subsequent nosocomial transmission within the dialysis unit and in shared shuttle buses to the hemodialysis unit. LIMITATIONS: Single-center study. CONCLUSIONS: Universal SARS-CoV-2 testing and universal droplet and contact precautions in the setting of an outbreak appeared to be effective in preventing further transmission.

Projecting the Number of Posttransplant Clinic Visits With a Rise in the Number of Kidney Transplants: A Case Study From Ontario, Canada.

BACKGROUND: In Ontario, kidney transplants have risen by 4% annually in recent years. An understanding of how this will affect the future annual number of posttransplant follow-up visits informs how to organize and deliver care. OBJECTIVE: We projected the required number of annual posttransplant follow-up nephrology visits to inform posttransplant care delivery. DESIGN: Population-based retrospective cohort study. SETTING: Linked databases from Ontario, Canada (population 14 million). PATIENTS: Incident kidney transplant recipients from years 2008 to 2013. MEASUREMENTS: Frequency, distance traveled, and current and projected visits for posttransplant follow-up. METHODS: Assuming a graft survival of 13 years and using the mean number of posttransplant clinic visits in years 1, 2, and 3, we forecasted the number of clinic visits needed in the year 2027. RESULTS: Using data from 2443 recipients, the mean (SD) number of clinic visits per recipient was 14.0 (9.2) in the first year after transplant, and 3.9 (6.2) and 3.0 (5.3) in the second and third year, respectively. If transplant rates rise by 4% per year until 2027, the estimated annual visits number will increase from 30 622 to 43 948. The median (25th, 75th percentile) distance between transplant center and patient's home was 30 (13, 65) km. The median round-trip travel distance for these visits in the first year after transplantation was 603 km per recipient, and median driving cost was Can$344 (2017). LIMITATIONS: Regarding patient expense, limitations include that distances traveled were calculated orthodromically, and we did not account for patient cost of follow-up beyond that of vehicular travel. Regarding follow-up projections, limitations include the assumption that graft life span will not change, follow-up patterns do not differ between donor kidney type, and we did not survey stakeholders as to their preferred method of follow-up. CONCLUSION: We quantified the increase in posttransplant visits when regional annual rates of transplantation rise. Strategies recognizing the burden of these visits may enhance patient-centered care, as it is unclear how some patients manage costs, nor how the current health care system will manage the demand.

CONTEXTE: Au cours des dernières années, le nombre de transplantations rénales a augmenté de 4 % annuellement en Ontario. Comprendre l'impact qu'aura cette augmentation sur le nombre annuel de visites de suivi post-transplantation dans les années à venir permettra d'organiser et de prodiguer les soins aux patients. OBJECTIF: Prévoir le nombre de visites de suivi post-transplantation qui seront requises dans le futur, de façon à orienter la prestation des soins. TYPE D'ÉTUDE: Étude de cohorte rétrospective basée sur une population. CADRE: Les bases de données couplées de l'Ontario, au Canada (population: 14 millions). SUJETS: Les receveurs d'une greffe rénale entre 2008 et 2013. MESURES: La fréquence des visites post-transplantation, la distance à parcourir pour s'y rendre, de même que leur nombre actuel et projeté. MÉTHODOLOGIE: Nous avons estimé le nombre de visites cliniques qui seront nécessaires en 2027 à partir d'une survie du greffon estimée à 13 ans et du nombre moyen de visites pour les années 1, 2 et 3 post-transplantation. RÉSULTATS: À partir des données de 2 443 receveurs, nous avons établi le nombre moyen (ET) de visites cliniques par receveur à 14,0 (9,2) pour la première année post-transplantation, à 3,9 (6,2) pour l'an 2 et à 3,0 (5,3) pour l'an 3. Si le nombre de greffes poursuit sa croissance au rythme de 4 % par an jusqu'en 2027, on estime que le nombre annuel de visites passera de 30 622 à 43 948. La distance médiane (25e, 75e percentile) entre le centre de greffe et la résidence du patient était de 30 km (13, 65). Dans l'année suivant la greffe, chaque patient avait parcouru une distance médiane totale (aller-retour) de 603 km et avait dépensé 344 $ (coût médian en dollars canadiens en 2017) pour ces déplacements. LIMITES: Les distances parcourues par les patients n'ont été calculées que de manière orthodromique et seules les dépenses liées aux déplacements en voiture ont été employées pour calculer les coûts aux patients. Les prévisions pour 2027 sont établies en tenant compte d'une survie du greffon qui demeurera stable, d'un schéma de suivi qui ne différera pas selon le type de donneur et du fait que nous n'avons pas questionné les intervenants quant à leur méthode de suivi préférée. CONCLUSION: Nous avons quantifié la hausse du nombre de visites post-transplantation en fonction de l'augmentation des taux de greffes annuels régionaux. Des stratégies reconnaissant le fardeau imposé par ces visites ont le potentiel d'améliorer les soins axés sur les patients puisqu'on ignore comment certains patients gèrent les coûts associés et comment le système de santé gèrera la demande.

Severe and near-fatal anaphylactic reactions triggered by chlorhexidine-coated catheters in patients undergoing renal allograft surgery: a case series.

PURPOSE: Although intraoperative anaphylaxis during surgery is a rare event, we describe five patients who experienced perioperative anaphylactic reactions during renal transplantation and were referred for investigation. CLINICAL FEATURES: Skin-prick and intradermal skin tests were done to investigate potential allergies to drugs given perioperatively prior to the development of anaphylaxis, including basiliximab, propofol, cefazolin, cis-atracurium, fentanyl, latex, remifentanil, and chlorhexidine. In addition, in vitro serologic testing for specific IgE was done in patients suspected to have had chlorhexidine anaphylaxis. All five patients were male, with a mean age of 48 yr (range 30-69). Skin testing for all drugs was non-reactive except for chlorhexidine, which was positive in four of five patients (one patient refused intradermal testing). In vitro test results for chlorhexidine-specific IgE were positive in all of the patients. Anesthetic records showed that intraoperative anaphylaxis had occurred immediately after insertion of a chlorhexidine-coated central venous catheter. CONCLUSIONS: Intraoperative insertion of chlorhexidine-coated central venous catheters can trigger life-threatening anaphylaxis in susceptible patients undergoing renal transplantation.

Safety and efficacy of prophylaxis for Pneumocystis jirovecii pneumonia involving trimethoprim-sulfamethoxazole dose reduction in kidney transplantation.

BACKGROUND: Trimethoprim-sulfamethoxazole (TMP-SMX) is the drug of choice for anti-Pneumocystis jirovecii pneumonia (PcP) prophylaxis in kidney transplant recipients (KTR). Post-transplant management balances preventing PcP with managing TMP-SMX-related adverse effects. TMP-SMX dose reduction addresses adverse effects but its implications to incident PcP are unclear. METHODS: We performed a retrospective review of all patients transplanted between 2011 and 2015 prescribed daily single strength TMP-SMX for twelve months post-transplantation as PcP prophylaxis. Actual TMP-SMX dose and duration, adverse effects, number of dose reductions and reasons, and PcP events were captured. Multivariate logistic regression analyses for risk factors associated with dose reduction were performed. RESULTS: Of 438 KTR, 233 (53%) maintained daily TMP-SMX and 205 (47%) sustained ≥1 dose reduction, with the point prevalence of a reduced dose regimen being between 18 and 25%. Median duration for daily TMP-SMX was 8.45/12 months, contributing 4137 patient-months daily TMP-SMX and 1110 patient-months with a reduced dose. PcP did not occur in any patients. There were 84 documented dose reductions for hyperkalemia and 102 for leukopenia, with 12 and 7 patients requiring TMP-SMX cessation. In multivariate analysis, a living donor transplant protected against hyperkalemia (Odds Ratio 0.46, 95% CI 0.26-0.83, p < 0.01) while acute rejection risked leukopenia (Odds Ratio 3.31, 95% CI 1.39-7.90, p = 0.006). CONCLUSIONS: TMP-SMX dose reduction is frequent in the first post-transplant year but PcP does not occur. To limit the need for TMP-SMX dose reduction due to adverse effects, a clinical trial comparing daily to thrice weekly single strength TMP-SMX in de-novo KTR is justified.

Ten years of Israel's organ transplant law: is it on the right track?

The Israeli organ donor law was established in 2008. In the ensuing 10 years there have been some improvements in deceased donation and living donor rates and a reduction in the unethical practice of transplant tourism. There is, however, controversy regarding increased access to transplant for those who have been living donors, who are family members of deceased donors, or who have registered their intent to donate. The issue of routine retrieval versus obtaining consent for organ donation has also been raised. This commentary will address these issue, and propose some steps for improvement of the current Israeli organ donation system.

Effect of organ donation after circulatory determination of death on number of organ transplants from donors with neurologic determination of death.

BACKGROUND: To increase the available pool of organ donors, Ontario introduced donation after circulatory determination of death (DCD) in 2006. Other jurisdictions have reported a decrease in donations involving neurologic determination of death (NDD) after implementation of DCD, with a drop in organ yield and quality. In this study, we examined the effect of DCD on overall transplant activity in Ontario. METHODS: We examined deceased donor and organ transplant activity during 3 distinct 4-year eras: pre-DCD (2002/03 to 2005/06), early DCD (2006/07 to 2009/10) and recent DCD (2010/11 to 2013/14). We compared these donor groups by categorical characteristics. RESULTS: Donation increased by 57%, from 578 donors in the pre-DCD era to 905 donors in the recent DCD era, with a 21% proportion (190/905) of DCD donors in the recent DCD era. However, overall NDD donation also increased. The mean length of hospital stay before declaration for NDD was 2.7 days versus 6.0 days before withdrawal of life support and subsequent asystole in cases of DCD. The average organ yield was 3.73 with NDD donation versus 2.58 with DCD (p < 0.001). Apart from hearts, all organs from DCD donors were successfully transplanted. From the pre-DCD era to the recent DCD era, transplant activity in each era increased for all solid-organ recipients, including heart (from 158 to 216), kidney (from 821 to 1321), liver (from 477 to 657) and lung (from 160 to 305). INTERPRETATION: Implementation of DCD in Ontario led to increased transplant activity for all solid-organ recipients. There was no evidence that the use of DCD was pre-empting potential NDD donation. In contrast to groups receiving other organs, heart transplant candidates have not yet benefited from DCD.

The role of thrombectomy and diffusion-weighted imaging with MRI in post-transplant renal vein thrombosis: a case report.

BACKGROUND: Surgical thrombectomy in the context of acute renal vein thrombosis (RVT) post-transplantation has had limited success, with considerable variation in the surgical techniques used. Unfortunately, it is usually followed by allograft nephrectomy within a few days if rapid allograft recovery does not ensue. We report a case of acute RVT in which nephrectomy was not performed despite a prolonged requirement for dialysis post-thrombectomy, but with recovery of renal function 2 weeks later. We also report the findings of serial MRI with diffusion-weighted imaging (DW-MRI) throughout the patient's recovery, which provided novel insights into allograft microvascular perfusion changes post-thrombectomy. CASE PRESENTATION: A 65-year old patient underwent living-unrelated kidney transplantation complicated by acute RVT. Surgical thrombectomy and irrigation led to a delayed, but significant, recovery of renal function. Serial non-contrast DW-MRI scanning was used to non-invasively assess microvascular renal blood flow post-operatively. Unlike standard Doppler ultrasonography, DW-MRI documented reduced microvascular perfusion initially, with gradual but incomplete recovery that mirrored the partial improvement in renal function. CONCLUSIONS: Our findings suggest that surgical thrombectomy may be more effective than previously described if followed by careful patient observation. Moreover, diffusion-weighted MRI appears to provide important insights into the pathophysiology of delayed graft function and deserves further investigation.

Study of Cardiovascular Outcomes in Renal Transplantation: A Prospective, Multicenter Study to Determine the Incidence of Cardiovascular Events in Renal Transplant Recipients in Ontario, Canada.

BACKGROUND: Renal transplant recipients (RTRs) are at significantly higher risk for morbidity and mortality compared with the general population, largely attributed to cardiovascular disease (CVD). Previous estimates of CVD events have come from health care databases and retrospective studies. OBJECTIVE: The objective of this study was to prospectively determine the prevalence of risk factors and incidence of CVD events in a Canadian cohort of RTRs. DESIGN: Study of Cardiovascular Outcomes in Renal Transplantation (SCORe) was a prospective, longitudinal, multicenter observational study. SETTING: Adult RTRs were recruited from 6 participating transplant sites in Ontario, Canada. PATIENTS: Eligible patients were those receiving a living or deceased donor renal transplant. Patients who received simultaneous transplant of any other organ were excluded. MEASUREMENTS: Primary outcomes included myocardial infarction (MI) defined by American College of Cardiology (ACC-MI) criteria, and major adverse cardiac events (MACE), defined as cardiovascular (CV) death, ACC-MI, coronary revascularization, and nonhemorrhagic stroke. CV events were adjudicated by a single, independent cardiologist. METHODS: CV and transplant-specific risk factors that predict MACE and ACC-MI were identified by stepwise regression analysis using the Cox proportional hazards model. RESULTS: A total of 1303 patients enrolled across 6 transplant centers were followed for 4.5 ± 1.6 years (mean ± SD). Incidence of MACE was 7.0%, with significant independent predictors/risk factors including age, diabetes, coronary revascularization, nonhemorrhagic stroke, and renal replacement therapy (RRT). ACC-MI incidence was 4.0%, with significant independent predictors/risk factors including age, coronary revascularization, and duration of RRT in excess of the median value (2.91 years). LIMITATIONS: Patients were recruited from a single province, so may not reflect the experience of RTRs in other areas of Canada. CONCLUSIONS: Using a prospective design and rigorous methodology, this study found that the incidence of CV events after renal transplantation was elevated relative to the general Canadian population and was comparable with that reported in patient registries, thus helping validate the utility of retrospective analysis in this field. SCORe highlights the importance of monitoring RTRs for traditional cardiac and transplant-specific CV risk factors to help prevent CV morbidity and mortality. Further research is needed to investigate a broader range of potential risk factors and their combined effects on incident CV events.

CONTEXTE: Les receveurs d'une greffe rénale présentent un risque significativement plus élevé de morbidité et de mortalité que l'ensemble de la population, ceci est en grande partie attribuable aux maladies cardiovasculaires. Les estimations antérieures du nombre d'événements cardiovasculaires proviennent des bases de données du système de santé et des résultats d'études rétrospectives. OBJECTIF DE L'ÉTUDE: L'étude visait à mesurer de manière prospective la prévalence des facteurs de risque et l'incidence des événements cardiovasculaires dans une cohorte de patients receveurs d'une greffe rénale au Canada. TYPE D'ÉTUDE: L'étude SCORe consistait en une étude observationnelle longitudinale menée de façon prospective au sein de plusieurs centres hospitaliers. CADRE DE L'ÉTUDE: Les patients adultes receveurs d'une greffe rénale ont été recrutés dans six hôpitaux de la province de l'Ontario, au Canada. PATIENTS: Les patients qui avaient reçu une greffe rénale provenant d'un donneur vivant ou décédé ont été inclus dans l'étude. Les patients qui avaient reçu une greffe simultanée de tout autre organe ont été exclus. MESURES: Les principaux critères retenus incluaient un infarctus du myocarde répondant aux critères établis par l'American College of Cardiology (ACC-MI), des événements cardiaques majeurs indésirables (MACE) tels que le décès d'origine cardiovasculaire, l'ACC-MI, la revascularisation coronarienne et l'AVC non hémorragique. Ces événements cardiovasculaires ont été constatés par un cardiologue indépendant. MÉTHODOLOGIE: Les facteurs de risque, cardiovasculaires ou spécifiques à la transplantation, qui permettent de prédire les MACE et l'ACC-MI ont été identifiés à l'aide du modèle de risques proportionnels de Cox pour l'analyse de régression en étapes. RÉSULTATS: Les 1 303 patients recrutés au sein des six centres hospitaliers ont été suivis sur une moyenne de 1,6 an (SD ± 4,5). L'incidence de MACE était de 7,0%, avec des indicateurs prévisionnels indépendants et des facteurs de risque significatifs incluant l'âge, le diabète, la revascularisation coronarienne, l'AVC non hémorragique et la thérapie de remplacement rénale. L'incidence d'ACC-MI était de 4,0%, avec des indicateurs prévisionnels indépendants et des facteurs de risque significatifs incluant l'âge, la revascularisation coronarienne et une durée pour la thérapie de remplacement rénal excédant la valeur médiane (2,91 ans). LIMITES DE L'ÉTUDE: Les patients ont été recrutés dans une seule province, les résultats sont susceptibles de ne pas être représentatifs de la situation des receveurs d'une greffe rénale ailleurs au Canada. CONCLUSIONS: Grâce à un plan d'étude prospectif et à une méthodologie rigoureuse, nous avons déterminé que l'incidence des événements cardiovasculaires chez les receveurs d'une greffe rénale a été plus élevée que dans la population canadienne en général. Nous avons également constaté qu'elle était comparable à l'incidence rapportée dans les registres de patients, ce qui vient confirmer l'utilité des études rétrospectives dans ce domaine. Les résultats obtenus lors de l'étude SCORe mettent en lumière l'importance de faire un suivi auprès des receveurs d'une greffe rénale afin de détecter les facteurs de risque cardiovasculaires ou spécifiques à l'intervention, et ainsi aider à prévenir la mortalité et la morbidité liées aux maladies cardiovasculaires. D'autres recherches sont nécessaires afin d'examiner un plus large éventail de facteurs de risques potentiels et leurs effets concomitants sur les événements cardiovasculaires.

The Impact of Total Gastrectomy on Pharmacokinetics in Kidney Transplant Immunosuppressive Drug Regimes: A Case Study.

BACKGROUND: Ensuring reliable gastrointestinal drug absorption of orally administered immunosuppressive medications posttransplant is critical to ensuring graft survival. METHODS: A 66-year-old man of East Asian origin with a previous total gastrectomy was evaluated for living donor kidney transplantation. Pretransplant pharmacokinetic testing was performed to determine the most appropriate posttransplant medication strategy. The Gastrointestinal Quality of Life Index and Gastrointestinal Rating Scale questionnaires were administered to gauge immunosuppressive medication-related side effects in the absence of a stomach. RESULTS: The patient's ability to absorb cyclosporin, tacrolimus (Tac), enteric-coated mycophenolate sodium (EC-MPS) and sirolimus (SRL) in oral dosage forms was well-preserved. Compared to nongastrectomy reference populations, the rate and extent of absorption of SRL and mycophenolic acid from EC-MPS were similar. The absorption of Tac and cyclosporin was greater than expected. Mycophenolate mofetil did not provide mycophenolic acid absorption as well as EC-MPS. The patient had worsened gastrointestinal symptoms with mycophenolate mofetil or EC-MPS in combination with Tac and cyclosporin, but this was not seen with isolated SRL. CONCLUSIONS: This case demonstrates that commonly used postkidney transplantation immunosuppressive regimes may be prescribed after total gastrectomy as long as their limitations are noted.