Association Between the Dialysate Bicarbonate and the Pre-dialysis Serum Bicarbonate Concentration in Maintenance Hemodialysis: A Retrospective Cohort Study.

Background: It is unclear whether the use of higher dialysate bicarbonate concentrations is associated with clinically relevant changes in the pre-dialysis serum bicarbonate concentration. Objective: The objective is to examine the association between the dialysate bicarbonate prescription and the pre-dialysis serum bicarbonate concentration. Design: This is a retrospective cohort study. Setting: The study was performed using linked administrative health care databases in Ontario, Canada. Patients: Prevalent adults receiving maintenance in-center hemodialysis as of April 1, 2020 (n = 5414) were included. Measurements: Patients were grouped into the following dialysate bicarbonate categories at the dialysis center-level: individualized (adjustment based on pre-dialysis serum bicarbonate concentration) or standardized (>90% of patients received the same dialysate bicarbonate concentration). The standardized category was stratified by concentration: 35, 36 to 37, and ≥38 mmol/L. The primary outcome was the mean outpatient pre-dialysis serum bicarbonate concentration at the patient level. Methods: We examined the association between dialysate bicarbonate category and pre-dialysis serum bicarbonate using an adjusted linear mixed model. Results: All dialysate bicarbonate categories had a mean pre-dialysis serum bicarbonate concentration within the normal range. In the individualized category, 91% achieved a pre-dialysis serum bicarbonate ≥22 mmol/L, compared to 87% in the standardized category. Patients in the standardized category tended to have a serum bicarbonate that was 0.25 (95% confidence interval [CI] = -0.93, 0.43) mmol/L lower than patients in the individualized category. Relative to patients in the 35 mmol/L category, patients in the 36 to 37 and ≥38 mmol/L categories tended to have a serum bicarbonate that was 0.70 (95% CI = -0.30, 1.70) mmol/L and 0.87 (95% CI = 0.14, 1.60) mmol/L higher, respectively. There was no effect modification by age, sex, or history of chronic lung disease. Limitations: We could not directly confirm that all laboratory measurements were pre-dialysis. Data on prescribed dialysate bicarbonate concentrations for individual dialysis sessions were not available, which may have led to some misclassification, and adherence to a practice of individualization could not be measured. Residual confounding is possible. Conclusions: We found no significant difference in the pre-dialysis serum bicarbonate concentration irrespective of whether an individualized or standardized dialysate bicarbonate was used. Dialysate bicarbonate concentrations ≥38 mmol/L (vs 35 mmol/L) may increase the pre-dialysis serum bicarbonate concentration by 0.9 mmol/L.

Contexte: On ignore si des concentrations plus élevées de bicarbonate dans le dialysat sont associées à des changements cliniquement significatifs dans le taux de bicarbonate sérique prédialyse. Objectif: Examiner l'association entre la prescription de bicarbonate du dialysat et le taux de bicarbonate sérique prédialyse. Conception: Étude de cohorte rétrospective. Cadre: Étude réalisée en Ontario (Canada) à partir des données administratives de santé. Sujets: Ont été inclus les adultes prévalents qui recevaient une hémodialyse chronique en centre le 1er avril 2020 (n=5 414). Mesures: Les sujets ont été regroupés dans les catégories suivantes de concentration en bicarbonate dans le dialysat utilisée dans leur unité de dialyse: individualisée (ajustée selon le taux de bicarbonate sérique prédialyse) ou normalisée (même concentration pour >90% des sujets). La catégorie « standardisée ¼ a été stratifiée selon la concentration: 35 mmol/L, 36 à 37 mmol/L et ≥38 mmol/L. Le principal critère d'évaluation était le taux moyen de bicarbonate sérique prédialyse en ambulatoire au niveau du patient. Méthodologie: Nous avons examiné l'association entre la catégorie de concentration en bicarbonate du dialysat et le taux de bicarbonate sérique prédialyse à l'aide d'un modèle linéaire mixte corrigé. Résultats: Pour toutes les catégories de concentration en bicarbonate du dialysat, le taux moyen de bicarbonate sérique prédialyse était dans la plage normale. Dans la catégorie « individualisée ¼, 91% des sujets avaient un taux de bicarbonate sérique prédialyse de ≥22 mmol/L, comparativement à 87% dans la catégorie « standardisée ¼. Les patients de la catégorie « standardisée ¼ tendaient à avoir un taux de bicarbonate sérique de 0,25 mmol/L (IC 95%: -0,93 à 0,43) inférieur à celui des patients de la catégorie « individualisée ¼. Comparé aux patients de la catégorie 35 mmol/L, les patients des catégories 36 à 37 mmol/L et ≥38 mmol/L tendaient respectivement à avoir un taux de bicarbonate sérique de 0,70 mmol/L (IC 95%: -0,30 à 1,70) et de 0,87 mmol/L (IC 95%: 0,14 à 1,60) plus élevé. L'âge, le sexe ou les antécédents de maladie pulmonaire chronique n'ont pas semblé modifier l'effet. Limites: Il n'a pas été possible de confirmer directement que toutes les mesures de laboratoire avaient été effectuées avant la dialyse. Les données sur les concentrations de bicarbonate prescrites pour les séances de dialyse individuelles n'étaient pas disponibles, ce qui peut avoir conduit à une classification erronée. De plus, l'observance d'une pratique d'individualisation n'a pas pu être mesurée. Une confusion résiduelle est possible. Conclusion: Nous n'avons observé aucune différence significative dans les taux de bicarbonate sériques prédialyse, qu'on ait utilisé une concentration individualisée ou standardisée de bicarbonate dans le dialysat. L'utilisation d'un dialysat à ≥38 mmol/L (c. 35 mmol/L) de bicarbonate peut entraîner une hausse de 0,9 mmol/L du taux de bicarbonate sérique prédialyse.

Renal Transplantation in HIV-positive and HIV-negative People With Advanced Stages of Kidney Disease: Equity in Transplantation.

Background: People with HIV are at a greater risk of end-stage kidney disease than the general population. Considering the risk of death after end-stage kidney disease, access to renal transplantation in people with HIV is critically important. Methods: We included all adult patients on chronic dialysis in Ontario, Canada, between 1 April 2007 and 31 December 2020. We determined the probability of kidney transplantation with competing risk of death over time since the initiation of dialysis by calculating the adjusted subdistribution hazard ratios (sdHR; 95% confidence interval [CI]). We also compared long-term renal allograft and posttransplant mortality outcomes between HIV-negative and HIV-positive persons. Results: Of 40 686 people (median age, 68 years; interquartile range, 57-77; 38.4% women), 173 were HIV-positive and 40 513 were HIV-negative. The incidence of kidney transplantation in HIV-negative and HIV-positive patients was 40.5 (95% CI, 39.4-41.6)/1000 person-years and 35.0 (95% CI, 22.8-53.7)/1000 person-years, respectively (P = .51). Considering the competing risk of death, HIV-positive people had a significantly lower chance of receiving kidney transplants than HIV-negative people (sdHR, 0.46 [95% CI, .30-.70]). The long-term allograft failure risk was not significantly different between HIV-negative and HIV-positive people, considering the competing risk of posttransplant death (sdHR, 1.71 [95% CI, .46-6.35]). Conclusions: Although the incidence and crude probability of kidney transplantation were similar among HIV-negative and HIV-positive persons in this cohort, those with HIV had a significantly lower likelihood of kidney transplantation than those without HIV. Having HIV was not significantly associated with a poor long-term allograft outcome compared with patients without HIV.

Public and patient perspectives on the use of clinical and administrative health data to identify and contact people at risk of future illness-The case of chronic kidney disease.

For decades, researchers have used linkable administrative health data for evaluating the health care system, subject to local privacy legislation. In Ontario, Canada, the relevant privacy legislation permits some organizations (prescribed entities) to conduct this kind of research but is silent on their ability to identify and contact individuals in those datasets. Following consultation with the Office of the Information and Privacy Commissioner of Ontario, we developed a pilot study to identify and contact by mail a sample of people at high risk for kidney failure within the next 2 years, based on laboratory and administrative data from provincial datasets held by ICES, to ensure they receive needed kidney care. Before proceeding, we conducted six focus groups to understand the acceptability to the public and people living with chronic kidney disease of direct mail outreach to people at high risk of developing kidney failure. While virtually all participants indicated they would likely participate in the study, most felt strongly that the message should come directly from their primary care provider or whoever ordered the laboratory tests, rather than from an unknown organization. If this is not possible, they felt the health care provider should be made aware of the concern related to their kidney health. Most agreed that, if health authorities could identify people at high risk of a treatable life-threatening illness if caught early enough, there is a social responsibility to notify people. While privacy laws allow for free flow of health information among health care providers who provide direct clinical care, the proposed case-finding and outreach falls outside that model. Enabling this kind of information flow will require greater clarity in existing laws or revisions to these laws. This also requires adequate notification and culture change for health care providers and the public around information uses and flows.

Comparison of Acute Health Care Utilization Between Patients Receiving In-Center Hemodialysis and the General Population: A Population-Based Matched Cohort Study From Ontario, Canada.

Background: Patients receiving maintenance hemodialysis have multiple comorbidities and are at high risk of presenting to the hospital. However, the incidence and cost of acute health care utilization in the in-center hemodialysis population and how this compares with other populations is poorly understood. Objective: To determine the rate, pattern, and cost of emergency department visits and hospitalizations in patients receiving in-center hemodialysis compared with a matched general population. Design: Population-based matched cohort study. Setting: We used linked administrative health care databases from Ontario, Canada. Patients: We included 25 379 patients (incident and prevalent) receiving in-center hemodialysis between January 1, 2010, and December 31, 2018. Patients were matched on birth date (±2 years), sex, and cohort entry date using a 1:4 ratio to 101 516 individuals from the general population. Measurements: Our primary outcomes were emergency department visits (allowing for multiple visits per individual) and hospital admissions from the emergency department. We also assessed all-cause hospitalizations, all-cause readmissions within 30 days of discharge from the original hospitalization, length of stay for hospital admissions (including multiple visits per individual), and the financial cost of these admissions. Methods: We presented the rate, percentage, median (25th, 75th percentiles), and incidence rate per 1000 person-years for emergency department visits and hospitalizations. Individual-level health care costs for emergency department visits and all-cause hospitalization were estimated using resource intensity weights multiplied by the cost per weighted case. Results: Patients receiving in-center hemodialysis had substantially more comorbidities (eg, diabetes) than the matched general population. Eighty percent (n = 20 309) of patients receiving in-center hemodialysis had at least 1 emergency department visit compared with 56% (n = 56 452) of individuals in the matched general population, over a median follow-up of 1.8 years (25th, 75th percentiles: 0.7, 3.6) and 5.2 (2.5, 8.4) years, respectively. The incidence rate of emergency department visits, allowing for multiple visits per individual, was 2274 per 1000 person-years (95% confidence interval [CI]: 2263, 2286) for patients receiving in-center hemodialysis, which was almost 5 times as high as the matched general population (471 per 1000 person-years; 95% CI: 469, 473). The rate of hospital admissions from the emergency department and the rate of all-cause hospital admissions in the in-center hemodialysis population was more than 7 times as high as the matched general population (hospital admissions from the emergency department: 786 vs 101 per 1000 person-years; all-cause hospital admissions: 1056 vs 139 per 1000 person-years). The median number of all-cause hospitalization days per patient year was 4.0 (0, 16.5) in the in-center hemodialysis population compared with 0 (0, 0.5) in the matched general population. The cost per patient-year for emergency department visits in the in-center hemodialysis population was approximately 5.5 times as high as the matched general population while the cost of hospitalizations in the in-center hemodialysis population was approximately 11 times as high as the matched general population (emergency department visits: CAN$ 1153 vs CAN$ 209; hospitalizations: CAN$ 21 151 vs CAN$ 1873 [all costs in 2023 CAN$]). Limitations: External generalizability and we could not determine whether emergency department visits and hospitalizations were preventable. Conclusions: Patients receiving in-center hemodialysis have high acute health care utilization. These results improve our understanding of the burden of disease and the associated costs in the in-center hemodialysis population, highlight the need to improve acute outcomes, and can aid health care capacity planning. Additional research is needed to address the risk of hospitalization after controlling for patient comorbidities. Trial registration: This is not applicable as this is a population-based matched cohort study and not a clinical trial.

Contexte: Les patients qui suivent des traitements d'hémodialyse d'entretien présentent de multiples comorbidités et sont hautement susceptibles de se présenter à l'hôpital. On en sait toutefois peu sur l'incidence de l'utilization des soins de santé aigus chez les patients hémodialysés en center, sur les coûts qui y sont associés, ainsi que sur la manière dont cela se compare à d'autres populations. Objectif: Déterminer, dans une population de patients hémodialysés en center, les taux d'hospitalizations et de visites aux urgences, leurs schémas et les coûts qui y sont associés, puis comparer ces résultats à ceux d'une population générale appariée. Type d'étude: Étudede cohorte populationnelle rétrospective. Cadre: Nous avons utilisé les bases de données couplées du système de santé de l'Ontario (Canada). Sujets: Nous avons inclus 25 379 patients (incidents et prévalents) qui recevaient des traitements d'hémodialyse en center entre le 1er janvier 2010 et le 31 décembre 2018. Les patients inclus ont été appariés,en fonction de leur date de naissance (± 2 ans), de leur sexe et de leur date d'entrée dans la cohorte, à 101 516 individus de la population générale dans un rapport de 1:4. Mesures: Nos principaux critères de jugement étaient les visites aux urgences (en permettant plusieurs visites par personne) et les admissions à l'hôpital à partir de l'urgence. Nous avons également évalué les hospitalizations toutes causes confondues, les réadmissions toutes causes confondues dans les 30 jours suivant le congé initial, la durée du séjour (en comptant les visites multiples par personne) et les coûts associés à ces admissions. Méthodologie: Nous avons présenté le nombre, le pourcentage, la médiane (25e et 75e percentile) et le taux d'incidence par 1000 années-personnes pour les visites aux urgences et les hospitalizations. Les coûts de santé par individu associés aux visites à l'urgence et aux hospitalizations toutes causes confondues ont été estimés en multipliant la pondération du volume des ressources par le coût pondéré par cas. Résultats: Les patients hémodialysés en center présentaient beaucoup plus de comorbidités (p. Ex. diabète) que la population générale appariée. Au cours d'un suivi médian respectif de 1,8 an (25e et 75e percentile: 0,7 et 3,6 ans) et de 5,2 ans (2,5 et 8,4 ans), 80 % (n=20 309) des patients hémodialysés en center ont visité l'urgence au moins une fois, contre 56 % (n= 56 452) des patients de la population générale appariée. Le taux d'incidence des visites aux urgences, en permettant plusieurs visites par personne, était de 2274 pour 1000 années-personnes (intervalle de confiance à 95% [IC 95%]: 2 263 à 2 286) chez les patients hémodialysés en center, soit presque cinq fois plus élevé que la population générale appariée (471 pour 1000 années-personnes; IC95 %: 469 à 473). Les taux d'admissions à partir de l'urgence et d'hospitalizations toutes causes confondues dans la population de patients hémodialysés en center étaient plus de sept fois plus élevés que dans la population générale appariée (admissions à partir de l'urgence: 786 contre 101 pour 1000 années-personnes; hospitalizations toutes causes confondues: 1056 contre 139 pour 1000 années-personnes). La durée médiane des hospitalizations toutes causes confondues par année-patient était de 4,0 jours (0 et 16,5 jours) chez les patients hémodialysés en center et de 0 jour (0 et 0,5 jour) dans la population générale appariée. Le coût par année-patient des visites à l'urgence chez les patients hémodialysés en center était environ 5,5 fois plus élevé que dans la population générale appariée, tandis que celui des hospitalizations était environ 11 fois plus élevé (visites à l'urgence: 1153 CAD contre 209 CAD; hospitalizations: 21 151 CAD contre 1873 CAD [coûts en dollars canadiens de 2023]). Limites: Généralisabilité externe; impossiblede déterminer si les visites aux urgences et les hospitalizations étaient évitables. Conclusion: Les patients hémodialysés en center sont de grands utilisateurs des soins de santé aigus. Ces résultats améliorent notre compréhension du fardeau de la maladie et des coûts associés à cette utilization dans cette population. Ces résultats soulignent également la nécessité d'améliorer les résultats des soins aigus et peuvent aider à la planification des capacités en matière de soins de santé. D'autres études sont nécessaires pour examiner le risque d'hospitalization après la gestion des comorbidités des patients.

Patient Care Gaps Prior to Maintenance Dialysis Initiation: A Population-Based Retrospective Study.

Background: Guidelines in Ontario, Canada, recommend timely referral for multidisciplinary kidney care to facilitate planned dialysis initiation. Many patients do not receive recommended multidisciplinary kidney care prior to dialysis. Objective: To better understand why this gap in pre-dialysis care exists, we conducted a study to describe the pathways by which patients initiate maintenance dialysis. Design: A retrospective cohort study. Setting: Population-based, using health care administrative databases from Ontario, Canada. Patients: Adults initiating maintenance dialysis from April 2016 to March 2019. Measurements and methods: Patients were grouped based on whether they received recommended multidisciplinary kidney care prior to dialysis initiation (at least 1 year of care with at least 2 visits). For those who did not receive recommended care, we grouped patients as having no identified care gap or into the following groups: (1) lack of timely chronic kidney disease (CKD) screening, (2) late nephrology referral (<1 year), or (3) late or no referral for multidisciplinary kidney care among patients followed by a nephrologist for at least 1 year. Results: A total of 9216 patients were included with a mean (standard deviation) age of 66 (15) years, and 61.5% were male. Of the total, 896 (9.7%) patients died, 7671 (83.2%) remained on dialysis at 90 days, and 649 (7.0%) had stopped dialysis due to kidney function recovery within 90 days. Of the 9216 patients, 5434 (59%) had not received recommended multidisciplinary kidney care. Among those without recommended care, there were 2251 (41.4%) patients with no identified care gaps, 1351 (24.9%) patients with a lack of timely CKD screening, 359 (6.6%) patients with late nephrology referral, and 1473 (27.1%) patients with late or no referral for multidisciplinary kidney care. Limitations: We could not determine if patients were referred but declined multidisciplinary kidney care. Conclusions: More than half of patients had not received recommended multidisciplinary kidney care. Many patients experienced an acute decline in kidney function, which may not be preventable, but in others, there were missed opportunities for CKD screening or early referral to nephrology, or at the level of nephrology practice for early referral for multidisciplinary care. This work could be used to inform policies aimed at improving increased uptake of multidisciplinary kidney care prior to dialysis.

Contexte: Les lignes directrices de l'Ontario (Canada) recommandent que les patients soient dirigés en temps opportun vers une prise en charge multidisciplinaire de la maladie rénale afin de faciliter l'initiation planifiée de la dialyze. Cette recommandation n'est toutefois pas appliquée pour de nombreux patients. Objectif: Afin de mieux comprendre ce qui explique cette lacune dans les soins de prédialyse, nous avons menu une étude visant à décrire le parcours des patients jusqu'à l'initiation de la dialyse chronique. Conception: Étude de cohorte rétrospective. Cadre: Étude populationnelle réalisée à partir des bases de données administratives de santé de l'Ontario (Canada). Sujets: Adultes ayant amorcé une dialyse d'entretien entre avril 2016 et mars 2019. Méthodologie et mesures: Les patients ont été groupés selon qu'ils avaient ou non reçu des soins multidisciplinaires recommandés avant l'initiation de la dialyse (au moins un an de soins incluant au moins deux visites). Les patients qui n'avaient pas reçu les soins recommandés ont été groupés soit comme ne présentant aucune lacune de soins identifiée, soit dans l'un des groupes suivants: i) absence de dépistage de l'IRC en temps opportun; ii) référence tardive en néphrologie (<1 an); iii) patients suivis depuis au moins un an par un néphrologue et non référés vers des soins multidisciplinaires ou référés tardivement. Résultats: En tout, 9 216 patients (61,5 % d'hommes) âgés en moyenne de 66 ans (écart-type: 15 ans) ont été inclus. De cette cohorte, 896 (9,7 %) patients sont décédés, 7 671 (83,2 %) étaient toujours sous dialyse après 90 jours et 649 (7,0 %) avaient cessé la dialyse dans les 90 jours en raison de la récupération de la fonction rénale. Le nombre total de patients n'ayant pas reçu les soins multidisciplinaires recommandés s'élevait à 5 434 (59 %). De ce nombre, 2 251 patients (41,4 %) ont été classés sans lacune de soins identifiée, 1 351 patients (24,9 %) n'avaient pas bénéficié d'un dépistage précoce de l'IRC, 359 patients (6,6 %) avaient été référés tardivement en néphrologie, et 1 473 patients (27,1 %) n'avaient pas été référés en soins multidisciplinaires ou l'avaient été tardivement. Limites: Nous n'avons pas été en mesure de déterminer si certains patients référés vers des soins multidisciplinaires avaient refusé ces soins. Conclusion: Plus de la moitié des patients n'ont pas reçu les soins multidisciplinaires recommandés avant la dialyse. De nombreux patients ont vécu une baisse rapide de leur fonction rénale, qui n'aurait possiblement pas pu être évitée, mais dans d'autres cas, des occasions de dépistage précoce de l'IRC ou de référence précoce en néphrologie ont été manquées. Au niveau de la pratique en néphrologie, là encore, des occasions de référence précoce vers des soins multidisciplinaires ont pu être manquées. Ces travaux pourraient éclairer les politiques visant à améliorer la prise en charge multidisciplinaire de la maladie rénale avant la dialyse.

Stroke Subtype Among Individuals With Chronic Kidney Disease.

Background: It is widely accepted that there is a stepwise increase in the risk of acute ischemic stroke with chronic kidney disease (CKD). However, whether the risk of specific ischemic stroke subtypes varies with CKD remains unclear. Objective: To assess the association between ischemic stroke subtypes (cardioembolic, arterial, lacunar, and other) classified using the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) and CKD stage. Design: retrospective cohort study. Setting: Ontario, Canada. Patients: A total of 17 434 adults with an acute ischemic stroke in Ontario, Canada between April 1, 2002 and March 31, 2013, with an estimated glomerular filtration rate (eGFR) measurement or receipt of maintenance dialysis captured in a stroke registry were included. Measurements: Kidney function categorized as an eGFR of ≥60, 30-59, <30 mL/min/1.73 m2, or maintenance dialysis. Ischemic stroke classified by TOAST included arterial, cardioembolic, lacunar, and other (dissection, prothrombotic state, cortical vein/sinus thrombosis, and vasculitis) types of strokes. Methods: Adjusted regression models. Results: In our cohort, 58.9% had an eGFR of ≥60, 34.7% an eGFR of 30-59, 6.0% an eGFR of <30 and 0.5% were on maintenance dialysis (mean age of 73 years; 48% women). Cardioembolic stroke was more common in patients with non-dialysis-dependant CKD (eGFR 30-59: 50.4%, adjusted odds ratio [OR] 1.20, 95% confidence interval [CI]: 1.02, 1.44; eGFR<30: 50.6%, OR 1.21, 95% CI: 1.02, 1.44), whereas lacunar stroke was less common (eGFR 30-59: 22.7% OR 0.85, 95% CI: 0.77, 0.93; eGFR <30: 0.73, 95% CI: 0.61, 0.88) compared with those with an eGFR ≥60. In stratified analyses by age and CKD, lacunar strokes were more frequent in those aged less than 65 years, whereas cardioembolic was higher in those aged 65 years and above. Limitations: TOAST classification was not captured for all patients. Conclusion: Non-dialysis CKD was associated with a higher risk of cardioembolic stroke, whereas an eGFR ≥60 mL/min/1.73 m2 was associated with a higher risk of lacunar stroke. Detailed stroke subtyping in CKD may therefore provide mechanistic insights and refocus treatment strategies in this high-risk population.

Contexte: Il est largement admis qu'il y a une augmentation progressive du risque d'accident vasculaire cérébral ischémique aigu en contexte d'insuffisance rénale chronique (IRC). On ignore cependant si le risque de certains sous-types particuliers d'AVC ischémiques varie en présence d'IRC. Objectif: Évaluer le lien entre le stade d'IRC et certains sous-types d'AVC ischémiques (cardioembolique, artériel, lacunaire et autres) classés selon l'essai TOAST (Trial of ORG 10172 in Acute Stroke Treatment). Type d'étude: Étude de cohorte retrospective. Cadre: Ontario (Canada). Sujets: Ont été inclus 17 434 adultes ayant subi un AVC ischémique aigu en Ontario (Canada) entre le 1er avril 2002 et le 31 mars 2013, et pour lesquels le registre d'AVC comportait une mesure du débit de filtration glomérulaire estimé (DFGe) ou une dialyze chronique. Mesures: La fonction rénale a été classée selon le DFGe (≥ 60 ml/min/1,73 m2 ­entre 30 et 59 ml/min/1,73 m2 ­<30 ml/min/1.73 m2) ou une dialyze chronique. Les types d'AVC ischémiques classés par l'essai TOAST comprenaient les AVC artériels, cardioemboliques, lacunaires et autres (dissection, état prothrombotique, thrombose de la veine/sinus cortical, vascularite). Méthodologie: Modèles de régression ajustés. Résultats: Dans notre cohorte (âge moyen de 73 ans; 48% de femmes), 58,9 % des patients avaient un DFGe ≥ 60 ml/min/1,73 m2; 34,7% avaient un DFGe entre 30 et 59 ml/min/1,73 m2; 6,0 % avaient un DFGe < 30 ml/min/1,73 m2 et 0,5 % des patients étaient en dialyze chronique En comparaison des patients ayant un DFGe ≥ 60 ml/min/1,73 m2, les AVC cardioemboliques étaient plus fréquents chez les patients atteints d'IRC sans dialyze (DFGe entre 30 et 59 ml/min/1,73 m2: 50,4%; rapport de cote corrigé [RCc] = 1,20; IC 95 % = 1,02-1,44­DFGe < 30 ml/min/1,73 m2: 50,6 %; RCc = 1,21; IC95% = 1,02-1,44) alors que les AVC lacunaires étaient moins fréquents [DFGe entre 30 et 59 ml/min/1,73 m2: 22,7%; RCc = 0,85; IC 95% = 0,77-0,93­DFGe < 30 ml/min/1,73 m2: RCc = 0,73; IC 95% = 0,61-0,88]. Dans les analyses stratifiées en fonction de l'âge et de l'IRC, les AVC lacunaires étaient plus fréquents chez les moins de 65 ans tandis que les AVC cardioemboliques étaient plus fréquents chez les plus de 65 ans. Limites: La classification TOAST n'était pas enregistrée pour tous les patients. Conclusion: L'IRC sans dialyze a été associée à un risque plus élevé d'AVC cardioembolique alors qu'un DFGe ≥ 60 ml/min/1.73 m2 a été associé à un risque plus élevé d'AVC lacunaire. Le sous-typage détaillé des AVC en contexte d'IRC pourrait donc fournir des informations mécanistiques et recentrer les stratégies de traitement dans cette population à haut risque.

Safety and Effectiveness of Rivaroxaban Versus Warfarin Across GFR Levels in Atrial Fibrillation: A Population-Based Study in Australia and Canada.

Rationale & Objective: The benefit-risk profile of rivaroxaban versus warfarin for atrial fibrillation (AF) in patients with chronic kidney disease is uncertain. We compared rivaroxaban with warfarin across the range of kidney function in adults with AF. Study Design: Multicenter retrospective cohort. Setting & Participants: Adults with AF and a measure of estimated glomerular filtration rate (eGFR); using administrative data from 5 jurisdictions across Australia and Canada (2011-2018). Kidney function was categorized as eGFR ≥60, 45-59, 30-44, and <30 mL/min/1.73 m2. Patients receiving dialysis and kidney transplant recipients were excluded. Exposures: New dispensation of either rivaroxaban or warfarin. Outcomes: Composite (1) effectiveness outcome (all-cause death, ischemic stroke, or transient ischemic attack) and (2) major bleeding events (intracranial, gastrointestinal, or other) at 1 year. Analytical Approach: Cox proportional hazards models accounting for propensity score matching were performed independently in each jurisdiction and then pooled using random-effects meta-analysis. Results: 55,568 patients (27,784 rivaroxaban-warfarin user matched pairs; mean age 74 years, 46% female, 33.5% with eGFR <60 mL/min/1.73 m2) experienced a total of 4,733 (8.5%) effectiveness and 1,144 (2.0%) bleeding events. Compared to warfarin, rivaroxaban was associated with greater or similar effectiveness across a broad range of kidney function (pooled HRs of 0.72 [95% CI, 0.66-0.78], 0.78 [95% CI, 0.58-1.06], 0.70 [95% CI, 0.57-0.87], and 0.78 [95% CI, 0.62-0.99]) for eGFR ≥60, 45-59, 30-44, and <30 mL/min/1.73 m2, respectively). Rivaroxaban was also associated with similar risk of major bleeding across all eGFR categories (pooled HRs of 0.75 [95% CI, 0.56-1.00], 1.01 [95% CI, 0.79-1.30], 0.87 [95% CI, 0.66-1.15], and 0.63 [95% CI, 0.37-1.09], respectively). Limitations: Unmeasured treatment selection bias and residual confounding. Conclusions: In adults with AF, rivaroxaban compared with warfarin was associated with lower or similar risk of all-cause death, ischemic stroke and transient ischemic attack and similar risk of bleeding across a broad range of kidney function. Plain-Language Summary: This real-world study involved a large cohort of 55,568 adults with atrial fibrillation from 5 jurisdictions across Australia and Canada. It showed that the favorable safety (bleeding) and effectiveness (stroke or death) profile of rivaroxaban compared with warfarin was consistent across different levels of kidney function. This study adds important safety data on the use of rivaroxaban in patients with reduced kidney function, including those with estimated glomerular filtration rate <30 mL/min/1.73 m2 in whom the risks and benefits of rivaroxaban use is most uncertain. Overall, the study supports the use of rivaroxaban as a safe and effective alternative to warfarin for atrial fibrillation across differing levels of kidney function.

The Incidence and Risk Factors for Emergency Department Imaging in Acute Renal Colic.

Objective: To determine the incidence of and risk factors for imaging in patients presenting to the emergency department (ED) with renal colic. Subject/Patients and Methods: We conducted a population-based cohort study in the province of Ontario, utilizing linked administrative health data. Patients who presented to an ED with renal colic between April 1, 2010, and June 30, 2020, were included. The rate of initial imaging (CT scans and ultrasound [U/S]) and repeat imaging within 30 days was determined. Generalized linear models were utilized to evaluate patient and institutional-level characteristics associated with imaging, and specifically CT vs U/S. Results: There were 397,491 index renal colic events, of which 67% underwent imaging (CT 68%, U/S 27%, and CT+U/S same day 5%). Repeat imaging was performed in 21% of events (U/S in 12.5%, CT in 8.4%) at a median of 10 days. Of those with an initial U/S, 28% had repeat imaging compared with 18.5% for those with an initial CT. Undergoing an initial CT was associated with being male, urban residence, later year of cohort entry, history of diabetes mellitus and inflammatory bowel disease, and presentation to nonacademic hospitals of larger size, or with a higher volume of ED visits. Conclusion: Two-thirds of renal colic patients underwent imaging, and CT was the most utilized modality. Patients undergoing an initial CT had a lower likelihood of repeat imaging within 30 days. The utilization of CT increased over time and was more common in males and those presenting to nonacademic hospitals of larger size, or with higher ED volumes. Our study highlights the patient- and institution-level factors that need to be targeted with prevention strategies to reduce the utilization of CT scans, when possible, for cost reduction and to minimize patient exposure to ionizing radiation.

Variation in Kidney Transplant Referral Across Chronic Kidney Disease Programs in Ontario, Canada.

Background: Eligible patients with kidney failure should have equal access to kidney transplantation. Transplant referral is the first crucial step toward receiving a kidney transplant; however, studies suggest substantial variation in the rate of kidney transplant referral across regions. The province of Ontario, Canada, has a public, single-payer health care system with 27 regional chronic kidney disease (CKD) programs. The probability of being referred for kidney transplant may not be equal across CKD programs. Objective: To determine whether there is variability in kidney transplant referral rates across Ontario's CKD programs. Design: Population-based cohort study using linked administrative health care databases from January 1, 2013, to November 1, 2016. Setting: Twenty-seven regional CKD programs in the province of Ontario, Canada. Patients: Patients approaching the need for dialysis (advanced CKD) and patients receiving maintenance dialysis (maximum follow-up: November 1, 2017). Measurements: Kidney transplant referral. Methods: We calculated the 1-year unadjusted cumulative probability of kidney transplant referral for Ontario's 27 CKD programs using the complement of Kaplan-Meier estimator. We calculated standardized referral ratios (SRRs) for each CKD program, using expected referrals from a 2-staged Cox proportional hazards model, adjusting for patient characteristics in the first stage. Standardized referral ratios with a value less than 1 were below the provincial average (maximum possible follow-up of 4 years 10 months). In an additional analysis, we grouped CKD programs according to 5 geographic regions. Results: Among 8641 patients with advanced CKD, the 1-year cumulative probability of kidney transplant referral ranged from 0.9% (95% confidence interval [CI]: 0.2%-3.7%) to 21.0% (95% CI: 17.5%-25.2%) across the 27 CKD programs. The adjusted SRR ranged from 0.2 (95% CI: 0.1-0.4) to 4.2 (95% CI: 2.1-7.5). Among 6852 patients receiving maintenance dialysis, the 1-year cumulative probability of transplant referral ranged from 6.4% (95% CI: 4.0%-10.2%) to 34.5% (95% CI: 29.5%-40.1%) across CKD programs. The adjusted SRR ranged from 0.2 (95% CI: 0.1-0.3) to 1.8 (95% CI: 1.6-2.1). When we grouped CKD programs according to geographic region, we found that patients residing in Northern regions had a substantially lower 1-year cumulative probability of transplant referral. Limitations: Our cumulative probability estimates only captured referrals within the first year of advanced CKD or maintenance dialysis initiation. Conclusions: There is marked variability in the probability of kidney transplant referral across CKD programs operating in a publicly funded health care system.

Contexte: Les patients atteints d'insuffisance rénale qui y sont admissibles devraient bénéficier d'un accès égal à la transplantation rénale. L'aiguillage vers un programme de transplantation est la première étape essentielle pour recevoir une greffe de rein. Des études suggèrent cependant qu'il existe des variations substantielles dans les taux d'aiguillage vers une greffe de rein selon les régions. La province de l'Ontario, au Canada, dispose d'un système public de santé à payeur unique comptant 27 programmes régionaux d'insuffisance rénale chronique (IRC). La probabilité d'être aiguillé vers une transplantation rénale n'est pas forcément la même dans tous les programmes d'IRC. Objectif: Déterminer s'il existe une variabilité dans les programmes d'IRC de l'Ontario en ce qui concerne les taux d'aiguillage vers une greffe de rein. Conception: Étude de cohorte représentative d'une population réalisée en Ontario (Canada) entre le 1er janvier 2013 et le 1er novembre 2016 à partir des données administratives en santé. Cadre: Les 27 programmes régionaux d'IRC de la province de l'Ontario (Canada). Sujets: Des patients approchant le besoin de dialyse (IRC de stade avancé) et des patients recevant des traitements de dialyse d'entretien (suivi maximum jusqu'au 1er novembre 2017). Mesures: L'aiguillage vers une greffe de rein. Méthodologie: Nous avons calculé la probabilité cumulative non ajustée d'être aiguillé à l'intérieur d'un an vers une transplantation rénale dans chacun des 27 programmes d'IRC de l'Ontario en utilisant le complément de l'estimateur Kaplan-Meier. Nous avons calculé les ratios d'aiguillage normalisés (SRR­Standardized Reference Ratios) des programmes d'IRC en utilisant les taux d'aiguillge attendus à partir d'un modèle de risques proportionnels de Cox en deux étapes, avec correction en fonction des caractéristiques du patient dans la première étape. Les ratios d'aiguillage normalisés d'une valeur inférieure à 1 étaient inférieurs à la moyenne provinciale (suivi maximum possible de 4 ans et 10 mois). Dans une analyse supplémentaire, nous avons regroupé les programmes d'IRC selon cinq régions géographiques. Résultats: Parmi les 8 641 patients atteints d'IRC de stade avancé, la probabilité cumulative d'aiguillage en un an pour une transplantation rénale variait de 0,9 % (IC 95 %: 0,2-3,7 %) à 21,0 % (IC 95 %: 17,5-25,2 %) pour l'ensemble des 27 programmes d'IRC. Le SRR corrigé variait de 0,2 (IC à 95 %: 0,1-0,4) à 4,2 (IC 95 %: 2,1-7,5). Parmi les 6 852 patients qui recevaient une dialyse d'entretien, la probabilité cumulative d'aiguillage en un an vers la transplantation variait de 6,4 % (IC 95 %: 4,0-10,2 %) à 34,5 % (IC 95 %: 29,5-40,1 %) pour l'ensemble des programmes d'IRC. Le SRR corrigé variait de 0,2 (IC 95 %: 0,1-0,3) à 1,8 (IC 95 %: 1,6-2,1). En regroupant les programmes d'IRC en fonction de la région géographique, nous avons constaté que les patients résidant dans les régions du Nord avaient une probabilité cumulative nettement plus faible d'être aiguillés vers la transplantation en un an. Limites: Nos estimations de la probabilité cumulative n'ont permis de saisir que les aiguillages au cours de la première année d'IRC de stade avancé ou de l'amorce d'une dialyse d'entretien. Conclusion: Il existe une variabilité marquée dans la probabilité d'être aiguillé vers une transplantation rénale dans les programmes d'IRC opérant dans un système de santé financé par l'État.

Kidney function and the comparative effectiveness and safety of direct oral anticoagulants vs. warfarin in adults with atrial fibrillation: a multicenter observational study.

AIMS: The aim of this study was to determine the comparative effectiveness and safety of direct oral anticoagulants (DOACs) and warfarin in adults with atrial fibrillation (AF) by level of kidney function. METHODS AND RESULTS: We pooled findings from five retrospective cohorts (2011-18) across Australia and Canada of adults with; a new dispensation for a DOAC or warfarin, an AF diagnosis, and a measure of baseline estimated glomerular filtration rate (eGFR). The outcomes of interest, within 1 year from the cohort entry date, were: (1) the composite of all-cause death, first hospitalization for ischaemic stroke, or transient ischaemic attack (effectiveness), and (2) first hospitalization for major bleeding defined as an intracranial, upper or lower gastrointestinal, or other bleeding (safety). Cox models were used to examine the association of a DOAC vs. warfarin with outcomes, after 1:1 matching via a propensity score. Kidney function was categorized as eGFR ≥60, 45-59, 30-44, and <30 mL/min/1.73 m2. A total of 74 542 patients were included in the matched analysis. DOAC initiation was associated with greater or similar effectiveness compared with warfarin initiation across all eGFR categories [pooled HRs (95% CIs) for eGFR categories: 0.74(0.69-0.79), 0.76(0.54-1.07), 0.68(0.61-0.75) and 0.86(0.76-0.98)], respectively. DOAC initiation was associated with lower or similar risk of major bleeding than warfarin initiation [pooled HRs (95% CIs): 0.75(0.65-0.86), 0.81(0.65-1.01), 0.82(0.66-1.02), and 0.71(0.52-0.99), respectively). Associations between DOAC initiation, compared with warfarin initiation, and study outcomes were not modified by eGFR category. CONCLUSION: DOAC use, compared with warfarin use, was associated with a lower or similar risk of all-cause death, ischaemic stroke, and transient ischaemic attack and also a lower or similar risk of major bleeding across all levels of kidney function.

Using Administrative Health Care Databases to Identify Patients With End-Stage Kidney Disease With No Recorded Contraindication to Receiving a Kidney Transplant.

Background: Administrative health care databases can be efficiently analyzed to describe the degree to which patients with end-stage kidney disease (ESKD) have access to kidney transplantation. Measures of access to transplantation are better represented when restricting to only those patients eligible to receive a kidney transplant. The way administrative data can be used to assess kidney transplant eligibility in the absence of clinical data has not been well described. Objective: To demonstrate a method that uses administrative health care databases to identify patients with ESKD who have no recorded contraindication to receiving a kidney transplant. Design and setting: Population-based cohort study using linked administrative health care databases in Ontario, Canada. Patients: Adult patients with ESKD approaching the need for dialysis (predialysis) or receiving maintenance dialysis between January 1, 2013 and March 31, 2015 in Ontario, Canada. Measurements: Recipient of a kidney-only or kidney-pancreas transplant. Methods: We assessed more than 80 baseline characteristics, including demographic information, comorbidities, kidney-specific characteristics, and referral and listing criteria for kidney transplantation. We compared these characteristics between patients who did and did not receive a kidney transplant. Results: We included 23 642 patients with ESKD (11 195 who were predialysis and 12 447 receiving maintenance dialysis). Over a median follow-up of 3.2 years (25th, 75th percentile: 1.3, 5.6), 3215 (13.6%) received a kidney-only or kidney-pancreas transplant. Of the studied characteristics available in administrative databases, >97% of patients with one or more of these characteristics did not receive a kidney transplant during follow-up: ESKD-modified Charlson Comorbidity Index score ≥7 (a higher score represents greater comorbidity), home oxygen use, age above 75 years, dementia, living in a long-term care facility, receiving at least one physician house call in the past year, and a combination of select malignancies (ie, lung, lymphoma, cervical, colorectal, liver, active multiple myeloma, and bladder cancer). Using these combined criteria reduced the total number of patients from 23 642 to 12 539 with no recorded contraindications to transplant (a 47% reduction), while the proportion who received a kidney transplant changed from 13.6% (denominator of 23 642) to 24.9% (denominator of 12 539). Limitations: Administrative databases are unable to capture all the complexities of determining transplant eligibility. Conclusion: We identified several criteria available within administrative health care databases that can be used to identify patients with ESKD who have no recorded contraindications to kidney transplant. These criteria could be applied when reporting measures of access to kidney transplantation that require knowledge of transplant eligibility.

Contexte: Les bases de données administratives en santé peuvent être analysées efficacement pour décrire le degré d'accès des patients atteints d'insuffisance rénale terminale (IRT) à une transplantation. Les mesures de l'accès à la transplantation sont mieux représentées lorsqu'on se limite aux patients admissibles pour recevoir une greffe rénale. On manque toutefois d'information sur la façon dont les données administratives peuvent être utilisées, en l'absence de données cliniques, pour évaluer l'admissibilité à une greffe rénale. Objectif: Démontrer une méthode utilisant les bases de données administratives en santé pour identifier les patients atteints d'IRT sans contre-indication à une greffe rénale. Type d'étude: Étude de cohorte représentative d'une population réalisée en Ontario (Canada) à partir des données administratives en santé. Sujets: Des patients ontariens (Canada) atteints d'IRT qui approchaient le besoin de dialyse (prédialyse) ou qui recevaient des traitements de dialyse d'entretien entre le 1er janvier 2013 et le 31 mars 2015. Mesures: Les receveurs d'une greffe de rein seulement ou de rein-pancréas. Méthodologie: Nous avons évalué plus de 80 caractéristiques initiales, notamment les données démographiques et les comorbidités des patients, et les caractéristiques particulières du rein; en plus des critères d'aiguillage et d'inscription pour une greffe rénale. Ces caractéristiques ont été comparées entre les patients greffés et ceux qui n'avaient pas reçu une greffe. Résultats: Nous avons inclus 23 642 patients atteints d'IRT (11 195 en prédialyse et 12 447 sous dialyse d'entretien). Pendant un suivi médian de 3,2 ans (25e percentile: 1,3 an; 75e percentile: 5,6 ans), 3 215 patients (13,6 %) ont reçu une greffe (rein seulement ou rein-pancréas). Plus de 97 % des patients présentant une ou plusieurs des caractéristiques suivantes, disponibles dans les bases de données, n'avaient pas reçu de greffe rénale pendant le suivi: avoir un score d'au moins 7 à l'indice de Charlson ajusté pour l'IRT (un score élevé représente une plus grande comorbidité), consommer de l'oxygène à domicile, avoir plus de 75 ans, souffrir de démence, vivre dans un établissement de soins de longue durée, avoir reçu au moins un appel du médecin au cours de la dernière année et présenter une combinaison de certaines tumeurs malignes (poumons, lymphome, col de l'utérus, colon, rectum, foie, vessie et myélome multiple actif). L'utilisation de ces critères combinés a réduit le nombre total de patients sans contre-indications à la transplantation de 23 642 à 12 539 (réduction de 47 %), faisant ainsi passer la proportion de patients ayant reçu une transplantation rénale de 13,6 % (dénominateur de 23 642) à 24,9 % (dénominateur de 12 539). Limites: Les bases de données administratives ne sont pas en mesure de saisir toutes les complexités liées à la détermination de l'admissibilité à une transplantation. Conclusion: Nous avons répertorié plusieurs critères disponibles dans les bases de données administratives en santé qui permettent d'identifier les patients atteints d'IRT sans contre-indications à la transplantation rénale. Ces critères pourraient être appliqués lors de la communication de mesures de l'accès à la transplantation rénale qui exigent de connaître l'admissibilité du patient à une transplantation.

Amiodarone, Verapamil, or Diltiazem Use With Direct Oral Anticoagulants and the Risk of Hemorrhage in Older Adults.

Background: Routinely used cardiac medications, based on pharmacokinetics, are hypothesized to increase drug levels of direct oral anticoagulants (DOACs), with the potential to increase the risk of hemorrhage. We set out to compare the risk for hemorrhage following initiation of amiodarone, verapamil, or diltiazem (moderate cytochrome P450 3A4 and/or P-glycoprotein activity) vs metoprolol or amlodipine (weak or no activity), among older adults prescribed DOACs. Methods: We conducted a population-based, retrospective cohort study of all adults (aged ≥ 66 years) on a DOAC (dabigatran, apixaban, rivaroxaban; n = 295,038) who were newly prescribed amiodarone (n = 4872), verapamil (n = 1284), or diltiazem (n = 14,638), compared with metoprolol or amlodipine, from Ontario, Canada (2009-2016). The outcome was hospital admission or emergency room visit with a major hemorrhage (upper or lower gastrointestinal tract, intracranial), examined using weighted models. Results: A total of 1737 hemorrhage events occurred (amiodarone, 80 [1.6%] vs metoprolol 503 [2.3%]; verapamil, 32 [2.5%] vs amlodipine, 406 [1.6%]; diltiazem, 312 [2.1%] vs amlodipine, 404 [1.5%]). The weighted risk of major hemorrhage was not elevated with amiodarone, verapamil, or diltiazem initiation in DOAC users, compared to metoprolol or amlodipine, during the full follow-up period (hazard ratio [HR; 95% confidence interval]: amiodarone HR 0.77 [0.61-0.97]; verapamil HR 1.32 [0.88-1.98]; diltiazem HR 0.99 [0.85-1.15]). This finding was consistent with a broader definition of bleeding, adjusting for kidney function, by DOAC type or dosage. Conclusions: Hemorrhage risk with amiodarone, verapamil, and diltiazem was similar to that with comparators, among DOAC users aged > 66 years.

Contexte: Les médicaments cardiaques couramment utilisés, selon la pharmacocinétique, devraient théoriquement augmenter les taux d'anticoagulants oraux directs (AOD), ce qui s'accompagne d'un risque accru d'hémorragie. Nous avons entrepris de comparer le risque d'hémorragie après l'instauration de l'amiodarone, du vérapamil ou du diltiazem (activité modérée du cytochrome P450 3A4 ou de la P-glycoprotéine) par rapport au métoprolol ou à l'amlodipine (activité faible ou nulle), chez des personnes âgées à qui l'on avait prescrit des AOD. Méthodologie: Nous avons mené une étude de cohortes rétrospective en population auprès de tous les adultes (âgés de 66 ans et plus) prenant un AOD (dabigatran, apixaban, rivaroxaban; n = 295 038) à qui l'on venait de prescrire de l'amiodarone (n = 4872), du vérapamil (n = 1284) ou du diltiazem (n = 14 638), comparativement au métoprolol ou à l'amlodipine, en Ontario, au Canada (2009-2016). Le critère d'évaluation était une admission à l'hôpital ou une consultation à l'urgence pour une hémorragie grave (voie gastro-intestinale supérieure ou inférieure, intracrânienne), examiné à l'aide de mo-dèles pondérés. Résultats: Au total, 1 737 événements hémorragiques sont survenus (amiodarone, 80 [1,6 %] contre métoprolol, 503 [2,3 %]; vérapamil, 32 [2,5 %] contre amlodipine, 406 [1,6 %]; diltiazem, 312 [2,1 %] contre amlodipine, 404 [1,5 %]). Le risque pondéré d'hémorragie grave ne s'est pas accru avec l'instauration de l'amiodarone, du vérapamil ou du diltiazem chez les utilisateurs d'AOD, comparativement au métoprolol ou à l'amlodipine, pendant toute la période de suivi (rapport des risques instantanés [RRI; intervalle de confiance à 95 %] : amiodarone : RRI 0,77 [0,61-0,97]; vérapamil : RRI 1,32 [0,88-1,98]; diltiazem : RRI 0,99 [0,85-1,15]). Ce résultat concorde avec une définition plus large du saignement, après ajustement pour la fonction rénale, par type ou posologie d'AOD. Conclusions: Le risque d'hémorragie associé à l'amiodarone, au vérapamil et au diltiazem était semblable à celui des médicaments de comparaison chez les utilisateurs d'AOD âgés de plus de 66 ans.

Hyperkalemia-Related Discontinuation of Renin-Angiotensin-Aldosterone System Inhibitors and Clinical Outcomes in CKD: A Population-Based Cohort Study.

RATIONALE & OBJECTIVE: Renin-angiotensin-aldosterone system (RAAS) inhibitors are evidence-based therapies that slow the progression of chronic kidney disease (CKD) but can cause hyperkalemia. We aimed to evaluate the association of discontinuing RAAS inhibitors after an episode of hyperkalemia and clinical outcomes in patients with CKD. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Adults in Manitoba (7,200) and Ontario (n = 71,290), Canada, with an episode of de novo RAAS inhibitor-related hyperkalemia (serum potassium ≥ 5.5 mmol/L) and CKD. EXPOSURE: RAAS inhibitor prescription. OUTCOME: The primary outcome was all-cause mortality. Secondary outcomes were cardiovascular (CV) mortality, fatal and nonfatal CV events, dialysis initiation, and a negative control outcome (cataract surgery). ANALYTICAL APPROACH: Cox proportional hazards models examined the association of RAAS inhibitor continuation (vs discontinuation) and outcomes using intention to treat approach. Sensitivity analyses included time-dependent, dose-dependent, and propensity-matched analyses. RESULTS: The mean potassium and mean estimated glomerular filtration rate were 5.8 mEq/L and 41 mL/min/1.73 m2, respectively, in Manitoba; and 5.7 mEq/L and 41 mL/min/1.73 m2, respectively, in Ontario. RAAS inhibitor discontinuation was associated with a higher risk of all-cause mortality (Manitoba: HR, 1.32 [95% CI, 1.22-1.41]; Ontario: HR, 1.47 [95% CI, 1.41-1.52]) and CV mortality (Manitoba: HR, 1.28 [95% CI, 1.13-1.44]; and Ontario: HR, 1.32 [95% CI, 1.25-1.39]). RAAS inhibitor discontinuation was associated with an increased risk of dialysis initiation in both cohorts (Manitoba: HR, 1.65 [95% CI, 1.41-1.85]; Ontario: HR, 1.11 [95% CI, 1.08-1.16]). LIMITATIONS: Retrospective study and residual confounding. CONCLUSIONS: RAAS inhibitor discontinuation is associated with higher mortality and CV events compared with continuation among patients with hyperkalemia and CKD. Strategies to maintain RAAS inhibitor treatment after an episode of hyperkalemia may improve clinical outcomes in the CKD population.

Opioid prescribing practices in chronic kidney disease: a population-based cohort study.

BACKGROUND: Chronic pain is common, and its management is complex in patients with chronic kidney disease (CKD), but limited data are available on opioid prescribing. We examined opioid prescribing for non-cancer and non-end-of-life care in patients with CKD. METHODS: This was a population-based retrospective cohort study using administrative databases in Ontario, Canada which included adults with CKD defined by an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 from 1 November 2012 to 31 December 2018 and estimated the proportion of opioid prescriptions (type, duration, dose, potentially inappropriate prescribing, etc.) within 1 year of cohort entry. Prescriptions had to precede dialysis, kidney transplant or death. RESULTS: We included 680 445 adults with CKD, and 198 063 (29.1%) were prescribed opioids. Codeine (14.9%) and hydromorphone (7.2%) were the most common opioids. Among opioid users, 24.3% had repeated or long-term use, 26.1% were prescribed high doses and 56.8% were new users. Opioid users were more likely to be female, had cardiac disease or a mental health diagnosis, and had more healthcare visits. The proportions for potentially inappropriate prescribing indicators varied (e.g. 50.1% with eGFR <30 were prescribed codeine, and 20.6% of opioid users were concurrently prescribed benzodiazepines, while 7.2% with eGFR <30 mL/min/1.73 m2 were prescribed morphine, and 7.0% were received more than one opioid concurrently). Opioid prescriptions declined with time (2013 cohort: 31.1% versus 2018 cohort: 24.5%; p <0.0001), as did indicators of potentially inappropriate prescribing. CONCLUSIONS: Opioid use was common in patients with CKD. While opioid prescriptions and potentially inappropriate prescribing have declined in recent years, interventions to improve pain management without the use of opioids and education on safer prescribing practices are needed.

Incidence and Outcomes Associated With Clostridioides difficile Infection in Solid Organ Transplant Recipients.

Importance: Little is known about the incidence and outcomes of Clostridioides difficile infection (CDI) in solid organ transplant (SOT) recipients. Objective: To estimate the CDI incidence and outcomes in SOT recipients. Design, Setting, and Participants: A population-based cohort study was conducted using administrative health care data for all Ontario, Canada, residents who received organ allografts from April 1, 2003, to December 31, 2017; March 31, 2020, was the end of the study period. Main Outcomes and Measures: The primary outcome was hospital admission with CDI diagnosis. The secondary outcomes included all-cause death, intensive care unit admission, acute kidney injury requiring dialysis, and fulminant CDI comprising any of the following: toxic megacolon, ileus, perforation, or colectomy. The association between short- vs long-term mortality (ie, death occurring within or after 90 days post-CDI) and the following variables was evaluated: age, sex, Deyo-Charlson Comorbidity Index, SOT type, early- vs late-onset CDI, fulminant CDI, intensive care unit admission, and acute kidney injury requiring acute dialysis. Results: Overall, 10 724 SOT recipients (6901 [64.4%] men; median age, 54 [IQR, 44-62] years) were eligible. Kidney transplant was the most common SOT type (6453 [60.2%]). The median follow-up time was 5.0 (IQR, 2.3-8.8) years, resulting in 61 987 person-years of follow-up. A total of 726 patients (6.8%) were hospitalized with CDI. The 1-year CDI incidence significantly increased in annual cohorts (ie, from 23.1; 95% CI, 12.8-41.8 per 1000 person-years in 2004 to 46.7; 95% CI, 35.0-62.3 per 1000 person-years in 2017; P = .001). Clostridioides difficile was associated with a 16.8% rate (n = 122) of 90-day mortality. In patients who underwent kidney transplant, CDI was typically late-onset (median interval, 2.2; IQR, 0.4-6.0 years) compared with recipients of other organs. Acute kidney injury requiring dialysis was significantly associated with short-term (adjusted odds ratio [aOR], 1.86; 95% CI, 1.07-3.26) and long-term (adjusted hazard ratio [aHR], 1.89; 95% CI, 1.29-2.78) mortality, and late-onset CDI was also significantly associated with a greater risk of short-term (aOR, 4.26; 95% CI, 2.51-7.22) and long-term (aHR, 2.49; 95% CI, 1.78-3.49) mortality. Conclusions and Relevance: In this study, increasing CDI trends in annual cohorts of SOT recipients were observed. Posttransplant CDI was associated with mortality, and late-onset CDI was associated with a greater risk of death than early-onset CDI. These findings suggest that preventive strategies should not be limited to the initial months following transplantation. Comprehensive therapeutic approaches targeting acute kidney injury risk factors in SOT recipients may reduce short- and long-term post-CDI mortality.

Proteinuria and venous thromboembolism in pregnancy: a population-based cohort study.

BACKGROUND: Pregnancy-associated venous thromboembolism (VTE) is associated with high morbidity and mortality. Identification of risk factors of VTE may lead to improved maternal and foetal outcomes. Proteinuria confers a pro-thrombotic state, however, its association with VTE in pregnancy remains unknown. We set out to assess the association of proteinuria and VTE during pregnancy. METHODS: We conducted a population-based, retrospective cohort study of all pregnant women (≥16 years of age) with a proteinuria measure within 20 weeks of conception (n = 306 244; mean age 29.8 years) from Ontario, Canada. Proteinuria was defined by any of the following: urine albumin:creatinine ratio ≥3 mg/mmol, urine protein:creatinine ratio ≥5 mg/mmol or urine dipstick proteinuria ≥1. The main outcome measure was a diagnosis of VTE up to 24-weeks post-partum. RESULTS: A positive proteinuria measurement occurred in 8508 (2.78%) women and was more common with a history of kidney disease, gestational or non-gestational diabetes mellitus and hypertension. VTE events occurred in 625 (0.20%) individuals, with a higher risk among women with positive proteinuria [32 events (0.38%)] compared with women without proteinuria [593 events (0.20%); inverse probability-weighted risk ratio 1.79 (95% confidence interval 1.25-2.57)]. The association was consistent using a more specific VTE definition, in the post-partum period, in high-risk subgroups (hypertension or diabetes) and when the sample was restricted to women with preserved kidney function. CONCLUSIONS: The presence of proteinuria in the first 20 weeks of pregnancy is associated with a significantly higher risk of VTE.

Comparison of childhood asthma incidence in 3 neighbouring cities in southwestern Ontario: a 25-year longitudinal cohort study.

BACKGROUND: Air pollution is a known trigger for exacerbations among individuals with asthma, but its role in the development of new-onset asthma is unclear. We compared the rate of new asthma cases in Sarnia, a city with high pollution levels, with the rates in 2 neighbouring regions in southwestern Ontario, Canada. METHODS: Using a population-based birth cohort design and linked health administrative data, we compared the hazard of incident asthma among children 0 to 10 years of age between those born in Lambton (Sarnia) and those born in Windsor and London-Middlesex, for the period Apr. 1, 1993, to Mar. 31, 2009. We used Cox proportional hazards models to adjust for year of birth and exposure to air pollutants (nitrogen dioxide, sulphur dioxide [SO2], ozone and small particulate matter [PM2.5]), as well as maternal, geographic and socioeconomic factors. RESULTS: Among 114 427 children, the highest incidence of asthma was in Lambton, followed by Windsor and London-Middlesex (30.3, 24.4 and 19.8 per 1000 person-years, respectively; p < 0.001). Relative to Lambton, the hazard of asthma, adjusted for socioeconomic and perinatal factors, was lower in Windsor (hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.67-0.77) and London-Middlesex (HR 0.65, 95% CI 0.61-0.69). Inclusion of air pollutants attenuated this relative difference in both Windsor (HR 0.79, 95% CI 0.62-1.01) and London-Middlesex (HR 0.89, 95% CI 0.64-1.24). INTERPRETATION: We identified a higher incidence of asthma among children born in Lambton (Sarnia) relative to 2 other regions in southwestern Ontario. Higher levels of air pollution (particularly SO2 and PM2.5) in this region, as experienced by children in their first year of life, may be contributory.

Ambulatory Treatments for RAAS Inhibitor-Related Hyperkalemia and the 1-Year Risk of Recurrence.

BACKGROUND AND OBJECTIVE: The optimal ambulatory management of renin-angiotensin-aldosterone system inhibitor (RAASi)-related hyperkalemia to reduce the risk of recurrence is unknown. We examined the risk of hyperkalemia recurrence on the basis of outpatient pharmacologic changes following an episode of RAASi-related hyperkalemia. DESIGN: We performed a population-based, retrospective cohort study of older adults (n=49,571; mean age 79 years) who developed hyperkalemia (potassium ≥5.3 mEq/L) while on a RAASi and were grouped as follows: no intervention, RAASi discontinuation, RAASi dose decrease, new diuretic, diuretic dose increase, or sodium polystyrene sulfonate within 30 days. The primary outcome was hyperkalemia recurrence, with secondary outcomes of cardiovascular events and all-cause mortality within 1 year. RESULTS: Among patients who received a pharmacologic intervention (23% of the cohort), RAASi discontinuation was the most commonly prescribed strategy (74%), followed by RAASi decrease (15%), diuretic increase (7%), new diuretic (3%), and sodium polystyrene sulfonate (1%). A total of 16,977 (34%) recurrent hyperkalemia events occurred within 1 year. Compared with no intervention (35%, referent), the cumulative incidence of recurrent hyperkalemia was lower with RAASi discontinuation (29%; hazard ratio, 0.82; 95% confidence interval, 0.78 to 0.85), whereas there was no difference with RAASi dose decrease (36%; hazard ratio, 0.94; 95% confidence interval, 0.86 to 1.02), new diuretic (32%; hazard ratio, 0.95; 95% confidence interval, 0.78 to 1.17), or diuretic increase (38%; hazard ratio, 0.99; 95% confidence interval, 0.87 to 1.12) and a higher incidence with sodium polystyrene sulfonate (55%; hazard ratio, 1.30; 95% confidence interval, 1.04 to 1.63). RAASi discontinuation was not associated with a higher risk of 1-year cardiovascular events (hazard ratio, 0.96; 95% confidence interval, 0.91 to 1.02) or all-cause mortality (hazard ratio, 1.05; 95% confidence interval, 0.96 to 1.15) compared with no intervention. CONCLUSIONS: Among older adults with RAASi-related hyperkalemia, RAASi discontinuation is associated with the lowest risk of recurrent hyperkalemia, with no apparent increase in short-term risks for cardiovascular events or all-cause mortality.

Dialysis Modality and Mortality in Heart Failure: A Retrospective Study of Incident Dialysis Patients.

INTRODUCTION: Prior studies reported lower mortality with hemodialysis (HD) compared to peritoneal dialysis (PD) in patients with heart failure (HF). We examined mortality rate by initial dialysis modality in incident dialysis patients with a history of HF using contemporary data and methods that ensure comparable HD and PD groups. METHODS: Retrospective cohort study using administrative databases in Ontario, Canada. Adults (age 50-80) with a history of HF who initiated maintenance dialysis between April 1, 2007 and March 31, 2016 were included. We excluded patients typically ineligible for PD as an initial modality (dialysis start in hospital, dementia, long-term care facility residency). We determined the cause-specific hazard ratio (transplant as a competing event) between initial dialysis modality (HD vs. PD) and all-cause mortality using an intention-to-treat approach. RESULTS: We included 2,199 patients with HF who initiated maintenance dialysis (77% HD and 23% PD). There were 1,152 (67.8%) and 340 (68.1%) mortality events over a median follow-up of 2.4 and 2.5 years in the HD and PD groups, respectively. Patients initiating HD versus PD was not associated with the mortality rate (adjusted hazard ratio 1.0, 95% CI 0.9-1.1). Similar results were seen in analyses censoring at modality switches and treating modality as time-varying. CONCLUSIONS: We found no difference in mortality by initial dialysis modality. Our data support the current practice of selecting dialysis modality based on patient preference for patients with pre-existing HF.

Potentially inappropriate prescribing in older adults with advanced chronic kidney disease.

BACKGROUND: Older adults with chronic kidney disease (CKD) are at heightened risk for polypharmacy. We examined potentially inappropriate prescribing in this population and whether introducing pharmacists into the ambulatory kidney care model was associated with improved prescribing practices. METHODS: Retrospective cohort study using linked administrative databases. We included patients with an eGFR ≤30 mL/min/1.73 m2 ≥66 years of age followed in multidisciplinary kidney clinics in Ontario, Canada (n = 25,016 from 28 centres). The primary outcome was the absence of a statin prescription or the receipt of a potentially inappropriate prescription defined by the American Geriatric Society Beers Criteria® and a modified Delphi panel that identified key drugs of concern in CKD. We calculated the crude cumulative incidence and incidence rate for the primary outcome and used change-point regression to determine if a change occurred following pharmacist introduction. RESULTS: There were 6,007 (24%) and 16,497 patients (66%) not prescribed a statin and with ≥1 potentially inappropriate prescription, respectively. The rate of potentially inappropriate prescribing was 125.6 per 100 person-years and was higher in more recent years. The change-point regression analysis included 2,275 patients from two centres. No immediate change was detected at pharmacist introduction, but potentially inappropriate prescribing was increasing pre-pharmacist introduction, and this rising trend was reversed post-pharmacist introduction. The incidence of potentially inappropriate prescribing still remained high post-pharmacist introduction. CONCLUSIONS: Potentially inappropriate prescribing practices were common. Incorporating pharmacists into the kidney care model may improve prescribing practices. The role of pharmacists in the ambulatory kidney care team warrants further investigation in a randomized controlled trial.