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.

Clinical Outcomes and Vaccine Effectiveness for SARS-CoV-2 Infection in People Attending Advanced CKD Clinics: A Retrospective Provincial Cohort Study.

BACKGROUND: People with advanced CKD are at high risk of mortality and morbidity from coronavirus disease 2019 (COVID-19). We measured rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe outcomes in a large population attending advanced CKD clinics during the first 21 months of the pandemic. We examined risk factors for infection and case fatality, and we assessed vaccine effectiveness in this population. METHODS: In this retrospective cohort study, we analyzed data on demographics, diagnosed SARS-CoV-2 infection rates, outcomes, and associated risk factors, including vaccine effectiveness, for people attending a province-wide network of advanced CKD clinics during the first four waves of the pandemic in Ontario, Canada. RESULTS: In a population of 20,235 patients with advanced CKD, 607 were diagnosed with SARS-CoV-2 infection over 21 months. The case fatality rate at 30 days was 19% overall but declined from 29% in the first wave to 14% in the fourth. Hospitalization and intensive care unit (ICU) admission rates were 41% and 12%, respectively, and 4% started long-term dialysis within 90 days. Significant risk factors for diagnosed infection on multivariable analysis included lower eGFR, higher Charlson Comorbidity Index, attending advanced CKD clinics for more than 2 years, non-White ethnicity, lower income, living in the Greater Toronto Area, and long-term care home residency. Being doubly vaccinated was associated with lower 30-day case fatality rate (odds ratio [OR], 0.11; 95% confidence interval [CI], 0.03 to 0.52). Older age (OR, 1.06 per year; 95% CI, 1.04 to 1.08) and higher Charlson Comorbidity Index (OR, 1.11 per unit; 95% CI, 1.01 to 1.23) were associated with higher 30-day case fatality rate. CONCLUSIONS: People attending advanced CKD clinics and diagnosed with SARS-CoV-2 infection in the first 21 months of the pandemic had high case fatality and hospitalization rates. Fatality rates were significantly lower in those who were doubly vaccinated. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_04_10_CJN10560922.mp3.

Effectiveness of Three Doses of mRNA COVID-19 Vaccines in the Hemodialysis Population during the Omicron Period.

BACKGROUND: Coronavirus disease 2019 (COVID-19) vaccine effectiveness studies in the hemodialysis population have demonstrated that two doses of mRNA COVID-19 vaccines are effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe complications when Alpha and Delta were predominant variants of concern. Vaccine effectiveness after a third dose versus two doses for preventing SARS-CoV-2 infection and severe COVID-19 in the hemodialysis population against Omicron is not known. METHODS: We conducted a retrospective cohort study in Ontario, Canada, between December 1, 2021, and February 28, 2022, in the maintenance hemodialysis population who had received two versus three doses of mRNA COVID-19 vaccines. COVID-19 vaccination, SARS-CoV-2 infection, and related hospitalization and death were determined from provincial databases. The primary outcome was the first RT-PCR confirmed SARS-CoV-2 infection, and the secondary outcome was a SARS-CoV-2-related severe outcome, defined as either hospitalization or death. RESULTS: A total of 8457 individuals receiving in-center hemodialysis were included. At study initiation, 2334 (28%) individuals received three doses, which increased to 7468 (88%) individuals by the end of the study period. The adjusted hazard ratios (aHR) for SARS-CoV-2 infection (aHR, 0.58; 95% confidence interval [CI], 0.50 to 0.67) and severe outcomes (hospitalization or death) (aHR, 0.40; 95% CI, 0.28 to 0.56) were lower after three versus two doses of mRNA vaccine. Prior infection, independent of vaccine status, was associated with a lower risk of reinfection, with an aHR of 0.44 (95% CI, 0.27 to 0.73). CONCLUSIONS: Three-dose mRNA COVID-19 vaccination was associated with lower incidence of SARS-CoV-2 infection and severe SARS-CoV-2-related outcomes during the Omicron period compared with two doses.

Early Experience with Modified Dose Nirmatrelvir/Ritonavir in Dialysis Patients with Coronavirus Disease 2019.

BACKGROUND: Nirmatrelvir/ritonavir was approved for use in high-risk outpatients with coronavirus disease 2019 (COVID-19). However, patients with severe CKD were excluded from the phase 3 trial, and the drug is not recommended for those with GFR <30 ml/min per 1.73 m 2 . On the basis of available pharmacological data, we developed a modified low-dose regimen of nirmatrelvir/ritonavir 300/100 mg on day 1, followed by 150/100 mg daily from day 2 to 5. In this study, we report our experience with this modified dose regimen in dialysis patients in the Canadian province of Ontario. METHODS: We included dialysis patients who developed COVID-19 and were treated with the modified dose nirmatrelvir/ritonavir regimen during a 60-day period between April 1 and May 31, 2022. Details of nirmatrelvir/ritonavir use and outcomes were captured manually, and demographic data were obtained from a provincial database. Data are presented with descriptive statistics. The principal outcomes we describe are 30-day hospitalization, 30-day mortality, and required medication changes with the modified dose regimen. RESULTS: A total of 134 dialysis patients with COVID-19 received nirmatrelvir/ritonavir during the period of study. Fifty-six percent were men, and the mean age was 64 years. Most common symptoms were cough and/or sore throat (60%). Medication interactions were common with calcium channel blockers, statins being the most frequent. Most patients (128, 96%) were able to complete the course of nirmatrelvir/ritonavir, and none of the patients who received nirmatrelvir/ritonavir died of COVID-19 in the 30 days of follow-up. CONCLUSIONS: A modified dose of nirmatrelvir/ritonavir use was found to be safe and well tolerated, with no serious adverse events being observed in a small sample of maintenance dialysis patients.

Infection Control Practices in In-Center Hemodialysis Units During Wave 1 of the COVID-19 Pandemic in Ontario, Canada: Research Letter.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a virus that caused coronavirus disease 2019 (COVID-19), the multisystem disease central to the COVID-19 pandemic. As patients receiving in-center maintenance hemodialysis require treatment 3 times weekly, they were unable to fully isolate. It was important for in-center hemodialysis units to implement robust infection control practices to ensure patient safety and minimize risk of transmitting SARS-CoV-2 among patients and staff. There are 27 renal programs within Ontario, Canada, providing care for about 9000 people across about 100 in-center hemodialysis units. These units are funded by the Ontario Renal Network (ORN), which is part of the provincial agency Ontario Health. Objective: The objective was to track infection control practices that were implemented by in-center hemodialysis units and be able to provide a descriptive narrative of the COVID-19 pandemic response of Ontario's hemodialysis units between March and September 2020. Methods: Between May and September 2020, data were collected from Ontario's 27 renal programs on the implementation of key infection control practices, including symptom screening, use of personal protective equipment, testing, practices specifically related to patients from congregate living settings, other prevention practices, and outbreak management. There were 4 data collection cycles, each approximately 1 month apart. The results were compiled and shared across the province, and infection control practices were also discussed at provincial COVID-19 teleconferences hosted by the ORN. Results: By March 2020, all but one renal program had implemented one or more forms of symptom screening, all renal programs had implemented physical distancing in waiting rooms and restricted visitors, and 74% of renal programs had implemented universal masking for all staff. By April 2020, 89% of renal programs had implemented universal masking for all patients, 52% had implemented enhanced contact and droplet precautions for suspected or positive cases, and 59% of renal programs tested all patients from congregate living settings regularly (with a low symptom threshold for testing). Infection control practices became more homogeneous across renal programs over time, and most practices were in place as of the last data collection. Conclusions: The renal system in Ontario was able to respond quickly within the first 2 months of the pandemic to minimize the spread of COVID-19 within in-center hemodialysis units. Through provincial teleconferences, infection control practices were shared across the province as the pandemic and hemodialysis unit responses evolved. This supported renal programs to advocate locally if their hospital was lagging in practices felt to be of value in other hemodialysis units. Although no direct correlation can be made regarding the implementation of infection control practices within in-center hemodialysis units and the number of COVID-19 cases in this population, the limited number of outbreaks in hemodialysis units may have been influenced by the proactive response of renal programs. Practices described in this article may support management and response to subsequent waves of COVID-19 or future similar infectious diseases.

Vaccine Effectiveness Against SARS-CoV-2 Infection and Severe Outcomes in the Maintenance Dialysis Population in Ontario, Canada.

BACKGROUND: Vaccination studies in the hemodialysis population have demonstrated decreased antibody response compared with healthy controls, but vaccine effectiveness for preventing SARS-CoV-2 infection and severe disease is undetermined. METHODS: We conducted a retrospective cohort study in the province of Ontario, Canada, between December 21, 2020, and June 30, 2021. Receipt of vaccine, SARS-CoV-2 infection, and related severe outcomes (hospitalization or death) were determined from provincial health administrative data. Receipt of one and two doses of vaccine were modeled in a time-varying cause-specific Cox proportional hazards model, adjusting for baseline characteristics, background community infection rates, and censoring for non-COVID death, recovered kidney function, transfer out of province, solid organ transplant, and withdrawal from dialysis. RESULTS: Among 13,759 individuals receiving maintenance dialysis, 2403 (17%) were unvaccinated and 11,356 (83%) had received at least one dose by June 30, 2021. Vaccine types were BNT162b2 (n=8455, 74%) and mRNA-1273 (n=2901, 26%); median time between the first and second dose was 36 days (IQR 28-51). The adjusted hazard ratio (HR) for SARS-CoV-2 infection and severe outcomes for one dose compared with unvaccinated was 0.59 (95% CI, 0.46 to 0.76) and 0.54 (95% CI, 0.37 to 0.77), respectively, and for two doses compared with unvaccinated was 0.31 (95% CI, 0.22 to 0.42) and 0.17 (95% CI, 0.1 to 0.3), respectively. There were no significant differences in vaccine effectiveness among age groups, dialysis modality, or vaccine type. CONCLUSIONS: COVID-19 vaccination is effective in the dialysis population to prevent SARS-CoV-2 infection and severe outcomes, despite concerns about suboptimal antibody responses.

Différences d'immunogénicité des vaccins anti-SRAS-CoV-2 mRNA-1273 (Moderna) et BNT162b2 (Pfizer-BioNTech) chez les patients dialysés.

CONTEXTE: Les différences d'immunogénicité entre les vaccins anti-SRAS-CoV-2 à ARNm n'ont pas été bien caractérisées chez les patients hémodialysés. Nous avons comparé la réponse sérologique chez les patients sous hémodialyse après la vaccination contre le SRAS-CoV-2 au moyen des vaccins BNT162b2 (Pfizer-BioNTech) et mRNA-1273 (Moderna). MÉTHODES: Nous avons procédé à une étude de cohorte observationnelle et prospective dans 2 centres universitaires de Toronto, au Canada, du 2 février au 20 juillet 2021, et avons inclus 129 et 95 patients qui ont reçu respectivement les vaccins anti-SRAS-CoV-2 BNT162b2 et mRNA-1273. Nous avons mesuré les taux d'anticorps IgG dirigés contre la protéine S (anti-S), contre le domaine de liaison au récepteur (ou RBD, pour receptor-binding domain [anti-RBD]) et contre la protéine de la nucléocapside (anti-N) du SRAS-CoV-2 6­7) puis 12 semaines après la deuxième dose de vaccin et nous avons comparé ces taux aux taux médians d'anticorps présents dans le sérum de 211 témoins convalescents qui avaient déjà contracté le SRAS-CoV-2. RÉSULTATS: Six à 7 semaines après la deuxième dose de vaccin, nous avons constaté que 51 patients sur 70 (73 %) ayant reçu le BNT162b2 et 83 patients sur 87 (95 %) ayant reçu le mRNA-1273, ont obtenu des taux équivalents à ceux du sérum de convalescents pour ce qui est de l'anticorps anti-S (p < 0,001). Chez ceux qui ont reçu le BNT162b2, 35 sur 70 (50 %) ont atteint le taux du sérum de convalescents pour l'anti-RBD, contre 69 sur 87 (79 %) de ceux qui ont reçu le mRNA-1273 (p < 0,001). Douze semaines après la deuxième dose, les taux d'anti-S et d'anti-RBD étaient significativement moindres chez les patients ayant reçu le BNT162b2 que chez ceux qui avaient reçu le mRNA-1273. Pour l'anti-S, 70 patients sur 122 (57,4 %) ayant reçu le BNT162b2 ont maintenu un taux équivalent à celui du sérum de convalescents, contre 68 sur 71 (96 %) de ceux qui avaient reçu le mRNA-1273 (p < 0,001). Pour l'anti-RBD, 47 patients sur 122 (38,5 %) ayant reçu le BNT162b2 ont maintenu des taux anti-RBD équivalant à celui du sérum de convalescents, contre 45 sur 71 (63 %) de ceux qui avaient reçu le mRNA-1273 (p = 0,002). INTERPRÉTATION: Chez les patients hémodialysés, le mRNA-1273 a généré une réponse humorale plus forte que le BNT162b2. Étant donné le déclin rapide de l'immunogénicité à 12 semaines chez les patients ayant reçu le BNT162b2, une troisième dose est recommandée chez les patients hémodialysés dans le cadre d'une première série, ce qui concorde avec les recommandations concernant d'autres populations vulnérables.

Acute kidney injury requiring renal replacement therapy in people with COVID-19 disease in Ontario, Canada: a prospective analysis of risk factors and outcomes.

BACKGROUND: Severely ill people with coronavirus disease 2019 (COVID-19) are at risk of acute kidney injury treated with renal replacement therapy (AKI-RRT). The understanding of the risk factors and outcomes for AKI-RRT is incomplete. METHODS: We prospectively collected data on the incidence, demographics, area of residence, time course, outcomes and associated risk factors for all COVID-19 AKI-RRT cases during the first two waves of the pandemic in Ontario, Canada. RESULTS: There were 271 people with AKI-RRT, representing 0.1% of all diagnosed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases. These included 10% of SARS-CoV-2 admissions to intensive care units (ICU). Median age was 65 years, with 11% <50 years, 76% were male, 47% non-White and 48% had diabetes. Overall, 59% resided in the quintile of Ontario neighborhoods with the greatest ethnocultural composition and 51% in the two lowest income quintile neighborhoods. Mortality was 58% at 30 days after RRT initiation, and 64% at 90 days. By 90 days, 20% of survivors remained RRT-dependent and 31% were still hospitalized. On multivariable analysis, people aged >70 years had higher mortality (odds ratio 2.4, 95% confidence interval 1.3, 4.6). Cases from the second versus the first COVID-19 wave were older, had more baseline comorbidity and were more likely to initiate RRT  >2 weeks after SARS-CoV-2 diagnosis (34% versus 14%; P < 0.001). CONCLUSIONS: AKI-RRT is common in COVID-19 ICU admissions. Residency in areas with high ethnocultural composition and lower socioeconomic status are strong risk factors. Late-onset AKI-RRT was more common in the second wave. Mortality is high and 90-day survivors have persisting high morbidity.

Acute kidney injury requiring renal replacement therapy in people with COVID-19 disease in Ontario, Canada: a prospective analysis of risk factors and outcomes

Background Severely ill people with COVID-19 are at risk of acute kidney injury treated with renal replacement therapy (AKI-RRT). Understanding of risk factors and outcomes for AKI-RRT is incomplete. Methods We prospectively collected data on the incidence, demographics, area of residence, time course, outcomes, and associated risk factors for all COVID-19 AKI-RRT cases during the first 2 waves of the pandemic in Ontario, Canada Results There were 271 people with AKI-RRT, representing 0.1% of all diagnosed SARS-CoV-2 cases. These included 10% of SARS-CoV-2 admissions to intensive care units (ICU). Median age was 65 years, with 11% under 50, 76% were male, 47% non-white, and 48% had diabetes. Overall, 59% resided in the quintile of Ontario neighborhoods with the greatest ethnocultural composition and 51% in the 2 lowest income quintile neighborhoods. Mortality was 58% at 30 days after RRT initiation, and 64% at 90 days. By 90 days, 20% of survivors remained RRT-dependent and 31% were still hospitalized. On multivariable analysis, people aged over 70 had higher mortality (odds ratio (OR) 2.4, 95% CI: 1.3, 4.6). Cases from the second versus the first COVID-19 wave were older, had more baseline co-morbidity, and were more likely to initiate RRT over 2 weeks after SARS-CoV-2 diagnosis (34% vs 14%, p < 0.001). Conclusions AKI-RRT is common in COVID-19 ICU admissions. Residency in areas with high ethnocultural composition and lower socioeconomic status are strong risk factors. Late onset AKI-RRT was more common in the second wave. Mortality is high and 90-day survivors have persisting high morbidity. Graphical Graphical

Province-Wide Prevalence Testing for SARS-CoV-2 of In-Center Hemodialysis Patients and Staff in Ontario, Canada: A Cross-Sectional Study.

BACKGROUND: People receiving in-center hemodialysis face a high risk for contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and experience poor outcomes. During the first wave of the coronavirus disease 2019 (COVID-19) pandemic in Ontario (between March and June 2020), it was unclear whether asymptomatic or presymptomatic cases were common and whether widespread testing of all dialysis patients and staff would identify cases earlier and prevent transmission. Ontario has a population of about 14.5 million. Approximately 8900 people receive dialysis across 102 in-center dialysis units. OBJECTIVE: The objective of this study was to determine participation rates for patients and staff in point prevalence testing in dialysis units across the province and to determine the prevalence of asymptomatic or presymptomatic infection. DESIGN: Cross-sectional study design. SETTING: In-center hemodialysis units at 27 renal programs across Ontario. PARTICIPANTS: Patients and staff in in-center dialysis units in Ontario. MEASUREMENTS: Participation rates, demographic data, SARS-CoV-2 positivity rates, and COVID-19-related symptom data. METHODS: From June 8 to 30, 2020, all in-center dialysis patients and staff in the Province of Ontario were requested to undergo a symptom screening assessment and nasopharyngeal swab. Testing was done using polymerase chain reaction to detect SARS-CoV-2. A standardized questionnaire of atypical and typical COVID-19-related symptoms was administered to patients, to assess for new or worsening COVID-19-related symptoms. RESULTS: Patient participation was 83% (7155 of 8612) of which 15 tests were positive: less than 5 (<0.07%) were new positive cases, 7 were false positive, and the remaining were recovered positives. Half of the new positive cases had symptoms. Common symptoms reported included fatigue (4%), falls (4%), runny nose (3%), dyspnea (3%), and cough (3%). Staff participation was 49% (2109 of 4325), and less than 5 (<0.24%) were asymptomatic positive. LIMITATIONS: As point prevalence testing was voluntary, not all patients and staff participated. Lower participation rate may be due to decreasing new cases in Ontario, and testing or pandemic fatigue, among other factors. This study did not use serology to identify prior infections because it was not widely available in Ontario. With respect to the standardized symptom questionnaire, it was only available in English and French and could not be tested due to the urgency of the initiative. CONCLUSIONS: Participation among patients in point prevalence testing was good, but participation among staff was relatively low. Asymptomatic positivity in the dialysis patient and staff population was rare during the first wave of the COVID-19 pandemic in Ontario.

COVID-19 chez les patients ontariens sous dialyse à long terme.

CONTEXTE: Les patients sous dialyse à long terme pourraient avoir un risque accru d'infection par le coronavirus du syndrome respiratoire aigu sévère 2 (SRAS-CoV-2), et de maladie et de mortalité associées. Nous avons voulu décrire l'incidence, les facteurs de risque et les issues de l'infection chez ces patients en Ontario (Canada). MÉTHODES: Nous avons utilisé des ensembles de données reliées pour comparer les caractéristiques de la maladie et la mortalité chez les patients sous dialyse à long terme en Ontario qui ont testé positif pour le SRAS-CoV-2 et ceux qui n'ont pas développé d'infection, entre le 12 mars et le 20 août 2020. Nous avons recueilli des données sur l'infection par le SRAS-CoV-2 de manière prospective. Nous avons évalué les facteurs de risque d'infection et de mortalité par des analyses de régression logistique multivariées. RÉSULTATS: Pendant la période à l'étude, 187 patients dialysés sur 12 501 (1,5 %) ont reçu un diagnostic d'infection par le SRAS-CoV-2. Parmi eux, 117 (62,6 %) ont été hospitalisés, et le taux de mortalité était de 28,3 %. Les facteurs prédictifs significatifs associés à l'infection incluaient l'hémodialyse dans un centre plutôt que la dialyse à domicile (rapport de cotes [RC] 2,54; intervalle de confiance [IC] à 95 % 1,59­4,05), le fait de vivre dans un établissement de soins de longue durée (RC 7,67; IC à 95 % 5,30­11,11), le fait d'habiter la région du Grand Toronto (RC 3,27; IC à 95 % 2,21­4,80), les ethnicités Noire (RC 3,05; IC à 95 % 1,95­4,77), du sous-continent indien (RC 1,70; IC à 95 % 1,02­2,81) et autres non blanches (RC 2,03; IC à 95 % 1,38­2,97) et les quintiles de revenu inférieurs (RC 1,82; IC à 95 % 1,15­2,89). INTERPRÉTATION: Les patients sous dialyse à long terme sont exposés à un risque accru d'infection par le SRAS-CoV-2 et de mortalité due à la maladie à coronavirus 2019. Il faudra travailler à éliminer les facteurs de risque d'infection et vacciner ces patients en priorité.

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.

COVID-19 in patients undergoing long-term dialysis in Ontario.

BACKGROUND: Patients undergoing long-term dialysis may be at higher risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and of associated disease and mortality. We aimed to describe the incidence, risk factors and outcomes for infection in these patients in Ontario, Canada. METHODS: We used linked data sets to compare disease characteristics and mortality between patients receiving long-term dialysis in Ontario who were diagnosed SARS-CoV-2 positive and those who did not acquire SARS-CoV-2 infection, between Mar. 12 and Aug. 20, 2020. We collected data on SARS-CoV-2 infection prospectively. We evaluated risk factors for infection and death using multivariable logistic regression analyses. RESULTS: During the study period, 187 (1.5%) of 12 501 patients undergoing dialysis were diagnosed with SARS-CoV-2 infection. Of those with SARS-CoV-2 infection, 117 (62.6%) were admitted to hospital and the case fatality rate was 28.3%. Significant predictors of infection included in-centre hemodialysis versus home dialysis (odds ratio [OR] 2.54, 95% confidence interval [CI] 1.59-4.05), living in a long-term care residence (OR 7.67, 95% CI 5.30-11.11), living in the Greater Toronto Area (OR 3.27, 95% CI 2.21-4.80), Black ethnicity (OR 3.05, 95% CI 1.95-4.77), Indian subcontinent ethnicity (OR 1.70, 95% CI 1.02-2.81), other non-White ethnicities (OR 2.03, 95% CI 1.38-2.97) and lower income quintiles (OR 1.82, 95% CI 1.15-2.89). INTERPRETATION: Patients undergoing long-term dialysis are at increased risk of SARS-CoV-2 infection and death from coronavirus disease 2019. Special attention should be paid to addressing risk factors for infection, and these patients should be prioritized for vaccination.