Effect and outcome of equity, diversity and inclusion programs in healthcare institutions: a systematic review protocol.

BACKGROUND: Equity, diversity and inclusion (EDI) in the healthcare field are crucial in meeting the healthcare needs of a progressively diverse society. In fact, a diverse healthcare workforce enables culturally sensitive care, promotes health equity and enhances the understanding of various needs and patients' viewpoints, potentially resulting in more effective patient treatment and improved patient outcomes. Despite this, information on the effectiveness of policies or programmes promoting EDI in health institutions is scarce. The objective of this systematic review is to assess the effects and outcomes of EDI programmes in healthcare institutions. METHODS: We will conduct Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant systematic review of studies on EDI programmes and describe their effects and outcomes in healthcare institutions. We will search PubMed, Scopus, Web of Science, CINAHL and PsycINFO databases. Selected studies will include randomised control trials (RCTs), non-RCTs and cross-sectional studies published either in English or French. Quality appraisal of studies and a narrative synthesis of extracted data will be conducted as well as a meta-analysis if possible. The quality of evidence in this review will be assessed by the Grades of Recommendation, Assessment, Development and Evaluation. ANTICIPATED RESULTS: We anticipate that this systematic review will reveal information on the effect of EDI programmes and their outcomes in healthcare institutions. We expect this information will provide insights that will lead to improvements in designing EDI policies and programmes in healthcare institutions. ETHICS AND DISSEMINATION: No ethical clearance is required for this study as no primary data will be collected. The final manuscript will be submitted to a journal for publication. In addition to this, the results of the study will also be disseminated through conference presentations to inform the research and clinical practice. REVIEW REGISTRATION: This protocol has been registered with the International Prospective Register of Systematic Reviews; registration number CRD42024502781.

Sex-Related Disparities in Cardiovascular Outcomes Among Older Adults With Late-Onset Hypertension.

BACKGROUND: It is unclear whether sex-based differences in cardiovascular outcomes exist in late-onset hypertension. METHODS: This is a population-based cohort study in Ontario, Canada of 266 273 adults, aged ≥66 years with newly diagnosed hypertension. We determined the incidence of the primary composite cardiovascular outcome (myocardial infarction, stroke, and congestive heart failure), all-cause mortality, and cardiovascular death by sex using Cox proportional hazard models adjusted for demographic factors and comorbidities. RESULTS: The mean age of the total cohort was 74 years, and 135 531 (51%) were female. Over a median follow-up of 6.6 (4.7-9.0) years, females experienced a lower crude incidence rate (per 1000 person-years) than males for the primary composite cardiovascular outcome (287.3 versus 311.7), death (238.4 versus 251.4), and cardiovascular death (395.7 versus 439.6), P<0.001. The risk of primary composite cardiovascular outcome was lower among females (adjusted hazard ratio, 0.75 [95% CI, 0.73-0.76]; P<0.001) than in males. This was consistent after adjusting for the competing risk of all-cause death with a subdistributional hazard ratio, 0.88 ([95% CI, 0.86-0.91]; P<0.001). CONCLUSIONS: Females had a lower risk of cardiovascular outcomes compared with males within a population characterized by advanced age and new hypertension. Our results highlight that the severity of outcomes is influenced by sex in relation to the age at which hypertension is diagnosed. Further studies are required to identify sex-specific variations in the diagnosis and management of late-onset hypertension due to its high incidence in this group.

Impact of the 2021 CKD-EPI eGFR Equation on Kidney Care Referral Criteria in Ontario, Canada: A Population-based Cross-sectional Study.

Background: In some jurisdictions, individuals become eligible or recommended for referral for different types of kidney care using criteria based on their estimated glomerular filtration rate (eGFR). Historically, GFR was estimated with an equation developed in 2009, which included a Black race term. An updated, race-free equation was developed in 2021. It is unclear how adoption of the 2021 equation will influence the number of individuals meeting referral criteria to receive different types of kidney care. Objective: To develop population-based estimates on how the number of individuals meeting the eGFR-based referral criteria to receive three different types of kidney care (nephrologist consultation, care in a multi-care specialty clinic, kidney transplant evaluation) changes when the 2021 versus 2009 equation is used to calculate eGFR. Design: Population-based, cross-sectional study. Setting: Ontario, Canada's most populous province with 14.2 million residents as of 2021. Less than 5% of Ontario's residents self-identify as being of Black race. Patients: Adults with at least one outpatient serum creatinine measurement in the 2 years prior to December 31, 2021. Measurements: Referral criteria to 3 different types of kidney care: nephrologist consultation, multi-care specialty clinic, and evaluation for a kidney transplant. The eGFR thresholds used to define referral eligibility or recommendation for these kidney health services were based on guidelines from Ontario's provincial renal agency. Methods: The number of individuals meeting referral criteria for the 3 different healthcare services was compared between the 2009 and 2021 equations, restricted to individuals not yet receiving that level of care. As individual-level race data were not available, estimates were repeated, randomly assigning a Black race status to 1%, 5%, and 10% of the population. Results: We had an outpatient serum creatinine measurement available for 1 048 110 adults. Using the 2009 equation, 37 345 individuals met the criteria to be referred to a nephrologist, 10 019 met the criteria to receive care in a multi-care specialty clinic, and 10 178 met the criteria to be referred for kidney transplant evaluation. Corresponding numbers with the 2021 equation (and the percent relative to the 2009 equation) were 26 645 (71.3%), 9009 (89.9%), and 8615 (84.6%) individuals, respectively. These numbers were largely unchanged when Black race was assumed in up to 10% of the population. Limitations: Referral criteria based solely on urine albumin-to-creatinine ratio were not assessed. Self-reported race data were unavailable. Conclusions: For healthcare planning, in regions where a minority of the population is Black, a substantial number of individuals may no longer meet referral criteria for different types of kidney healthcare following adoption of the new 2021 eGFR equation.

Contexte: Dans certaines régions, les individus sont dirigés vers différents types de soins rénaux, ou y deviennent admissibles, selon des critères fondés sur le débit de filtration glomérulaire estimé (DFGe). Historiquement, le DFG était estimé avec une équation développée en 2009 comportant un terme qui tenait compte du fait d'être une personne de race noire. Une nouvelle équation sans mention de la race a été développée en 2021. Il est difficile de savoir comment l'adoption de l'équation de 2021 influencera le nombre de personnes qui répondront aux critères pour recevoir divers types de soins rénaux. Objectifs: Établir des estimations populationnelles de la variation du nombre de personnes qui répondent aux critères d'orientation fondés sur le DFGe pour recevoir trois différents types de soins rénaux (consultation avec un néphrologue, soins dans une clinique multidisciplinaire spécialisée, évaluation pour une transplantation rénale) selon que le DFGe est calculé avec l'équation de 2021 ou de 2009. Conception: Étude populationnelle transversale rétrospective. Cadre: L'Ontario, la province la plus peuplée du Canada avec 14,2 millions d'habitants en 2021. Moins de 5 % des résidents de l'Ontario s'identifient comme étant de race noire. Sujets: Des adultes avec au moins une mesure de la créatinine sérique en ambulatoire au cours des deux ans précédant le 31 décembre 2021. Mesures: Les critères d'orientation vers trois différents types de soins rénaux : consultation avec un néphrologue, soins en clinique multidisciplinaire spécialisée et évaluation pour une transplantation rénale. Les seuils de DFGe utilisés pour définir l'admissibilité à ­ ou l'orientation vers ­ ces services de santé rénale étaient fondés sur les lignes directrices de l'agence provinciale de soins rénaux de l'Ontario. Méthodologie: On a comparé les nombres d'individus répondant aux critères d'orientation pour les trois différents services de santé, calculés avec les équations de 2009 et de 2021, en se limitant aux personnes qui ne recevaient pas encore de tels soins. Les données individuelles sur la race n'étant pas disponibles, les estimations ont été répétées en attribuant aléatoirement un statut de race noire à 1 %, à 5 % et à 10 % de la population étudiée. Résultats: Une mesure de la créatinine sérique en ambulatoire était disponible pour un total de 1 048 110 adultes. Avec l'équation de 2009, 37 345 personnes répondaient aux critères pour être dirigées vers un néphrologue, 10 019 répondaient aux critères pour recevoir des soins dans une clinique multidisciplinaire spécialisée et 10 178 répondaient aux critères pour être évaluées pour une transplantation rénale. Avec l'équation de 2021, ces mêmes nombres de personnes (pourcentage par rapport à l'équation de 2009) étaient respectivement 26 645 (71,3 %), 9 009 (89,9 %) et 8 615 (84,6 %). Des chiffres qui sont demeurés majoritairement inchangés même en assumant une proportion de jusqu'à 10 % de personnes de race noire dans la population. Limites: Les critères d'orientation fondés uniquement sur le rapport albumine/créatinine urinaire n'ont pas été évalués. Les données autodéclarées sur la race n'étaient pas disponibles. Conclusion: Pour la planification des soins de santé, dans les régions où une minorité de la population est noire, un nombre important de personnes pourraient ne plus répondre aux critères d'orientation vers différents types de soins rénaux après l'adoption de l'équation de 2021 pour le calcul du DFGe.

Psychometric Evaluation of the Multidimensional Scale-Uremic Pruritus in Dialysis Patients (UP-Dial): Comparison in Hemodialysis and Peritoneal Dialysis Patients with Chronic Pruritus.

BACKGROUND: High-quality patient-reported outcome (PRO) measures for dialysis patients with chronic pruritus are urgently needed. However, no known, well-validated multidimensional tools have been investigated to measure pruritus symptoms in dialysis patients. OBJECTIVES: To examine the psychometric properties of a multidimensional tool of chronic pruritus, the Uremic Pruritus in Dialysis (UP-Dial) 14-item, by comparing hemodialysis and peritoneal dialysis modality. METHODS: This validation study used data from the Thai Renal Outcomes Research-Uremic Pruritus, a prospective, multicenter, longitudinal study. Data for this study were collected from February 1, 2019, to May 31, 2022. The adult sample of 226 hemodialysis and 327 peritoneal dialysis patients fulfilled the criteria of chronic pruritus based on the International Forum for the Study of Itch. Psychometric properties of the UP-Dial included validity and reliability, as measured across hemodialysis and peritoneal dialysis patients. Patients completed a set of anchor-based measurement tools, including global itching, Dermatology Life Quality Index (DLQI), EuroQoL-5 dimension-5 level (EQ-5D-5L), Kidney Disease Quality of Life-36 (KDQOL-36), Pittsburgh Sleep Quality Index (PSQI), global fatigue, Somatic Symptom Scale-8 (SSS-8), and Patient Health Questionnaire-9 (PHQ-9). RESULTS: From the patient's perspective, face validity was satisfactory for both dialysis samples. Psychometric analyses of the UP-Dial for each dialysis sample had good convergent validity. Spearman rho correlations indicate a positively strong correlation (0.73 to 0.74) with global itching, a positively moderate correlation (0.33 to 0.58) with DLQI, PSQI, global fatigue, SSS-8, and PHQ-9, and a negatively moderate correlation (-0.39 to -0.58) with EQ-5D-5L and KDQOL-36. The discriminant validity was satisfactory with a group of moderate and severe burden of pruritus for both dialysis samples. For scale reliability, the UP-Dial revealed excellent internal consistency (Cronbach's α = 0.89 and McDonald's ω = 0.90) and reproducibility (intraclass correlation: 0.84 to 0.85) for both dialysis samples. Regarding psychometric properties, no statistically significant differences between dialysis samples were observed (all P > 0.05). CONCLUSIONS: The findings reaffirm good measurement properties of the UP-Dial 14-items in hemodialysis and peritoneal dialysis patients with chronic pruritus. These suggest a transferability of the UP-Dial as a PRO measure in clinical trial and practice settings.

Social determinants of health and dialysis modality selection in patients with advanced chronic kidney disease: A retrospective cohort study.

BACKGROUND: Social determinants of health are non-medical factors that impact health. For patients with chronic kidney disease (CKD) progressing to kidney failure, the influence of social determinants of health on dialysis modality selection (haemodialysis vs. peritoneal dialysis (PD)) is incompletely understood. METHODS: Retrospective cohort study of 981 consecutive patients with advanced CKD referred to the Ottawa Hospital Multi-Care Kidney Clinic (Canada) who progressed to dialysis from 2010 to 2021. Multivariable logistic regression was used to measure odds ratios (OR) for the associations between social determinants of health (education, employment, marital status and residence) and modality of dialysis initiation. RESULTS: The mean age and estimated glomerular filtration rate were 64 and 18 mL/min/1.73 m2, respectively. Not having a high school degree was associated with lower odds of initiating dialysis via PD compared to having a college degree (29% vs. 48%, OR 0.55 (95% confidence interval (CI) 0.34-0.88)). Unemployment was associated with lower odds of initiating dialysis via PD compared to active employment (38% vs. 62%, OR 0.40 (95% CI 0.27-0.60)). Being single was associated with lower odds of initiating dialysis via PD compared to being married (35% vs. 48%, adjusted OR 0.52 (95% CI 0.39-0.70)). Living alone at home was associated with lower odds of initiating dialysis via PD compared to living at home with family (33% vs. 47%, adjusted OR 0.55 (95% CI 0.39-0.78)). CONCLUSIONS: Social determinants of health including education, employment, marital status and residence are associated with dialysis modality selection. Addressing these 'upstream' social factors may allow for more equitable outcomes during the transition from advanced CKD to kidney failure.

Has the time come for age-adapted glomerular filtration rate criteria to define chronic kidney disease: how soon is now?

PURPOSE OF REVIEW: The conventional definition of chronic kidney disease (CKD) primarily relies on the identification of albuminuria or a decline in estimated glomerular filtration rate (eGFR). For many years, a straightforward eGFR threshold of <60 ml/min/1.73 m 2 has been widely adopted as the standard for defining CKD. Nonetheless, this criterion fails to consider the natural aging process of the kidney, and this oversight may affect the accurate diagnosis of kidney disease particularly at the extremes of age. RECENT FINDINGS: The fixed eGFR threshold of <60 ml/min/1.73 m 2 for defining CKD misses crucial opportunities for risk prevention. Studies have revealed that the eGFR threshold at which the risks for adverse long-term health outcomes such as mortality, cardiovascular events, and kidney failure begin to rise varies substantially by age. Specifically, this threshold is lower for the elderly and higher for young adults. Consequently, this results in the over-diagnosis of kidney disease in the elderly and the under-diagnosis of kidney disease in young adults. SUMMARY: To address these limitations of the current CKD definition, we discuss a number of proposed age-adapted eGFR criteria and weigh their pros and cons against the current, simple, and universally accepted approach.

Subclinical Primary Aldosteronism and Cardiovascular Health: A Population-Based Cohort Study.

BACKGROUND: Primary aldosteronism, characterized by overt renin-independent aldosterone production, is a common but underrecognized form of hypertension and cardiovascular disease. Growing evidence suggests that milder and subclinical forms of primary aldosteronism are highly prevalent, yet their contribution to cardiovascular disease is not well characterized. METHODS: This prospective study included 1284 participants between the ages of 40 and 69 years from the randomly sampled population-based CARTaGENE cohort (Québec, Canada). Regression models were used to analyze associations of aldosterone, renin, and the aldosterone-to-renin ratio with the following measures of cardiovascular health: arterial stiffness, assessed by central blood pressure (BP) and pulse wave velocity; adverse cardiac remodeling, captured by cardiac magnetic resonance imaging, including indexed maximum left atrial volume, left ventricular mass index, left ventricular remodeling index, and left ventricular hypertrophy; and incident hypertension. RESULTS: The mean (SD) age of participants was 54 (8) years and 51% were men. The mean (SD) systolic and diastolic BP were 123 (15) and 72 (10) mm Hg, respectively. At baseline, 736 participants (57%) had normal BP and 548 (43%) had hypertension. Higher aldosterone-to-renin ratio, indicative of renin-independent aldosteronism (ie, subclinical primary aldosteronism), was associated with increased arterial stiffness, including increased central BP and pulse wave velocity, along with adverse cardiac remodeling, including increased indexed maximum left atrial volume, left ventricular mass index, and left ventricular remodeling index (all P<0.05). Higher aldosterone-to-renin ratio was also associated with higher odds of left ventricular hypertrophy (odds ratio, 1.32 [95% CI, 1.002-1.73]) and higher odds of developing incident hypertension (odds ratio, 1.29 [95% CI, 1.03-1.62]). All the associations were consistent when assessing participants with normal BP in isolation and were independent of brachial BP. CONCLUSIONS: Independent of brachial BP, a biochemical phenotype of subclinical primary aldosteronism is negatively associated with cardiovascular health, including greater arterial stiffness, adverse cardiac remodeling, and incident hypertension.

A Canadian Commentary on the NKF-ASN Task Force Recommendations on Reassessing the Inclusion of Race in Diagnosing Kidney Disease.

In 2021, a committee was commissioned by the Canadian Society of Nephrology to comment on the 2021 National Kidney Foundation-American Society of Nephrology Task Force recommendations on the use of race in glomerular filtration rate estimating equations. The committee met on numerous occasions and agreed on several recommendations. However, the committee did not achieve unanimity, with a minority group disagreeing with the scope of the commentary. As a result, this report presents the viewpoint of the majority members. We endorsed many of the recommendations from the National Kidney Foundation-American Society of Nephrology Task Force, most importantly that race should be removed from the estimated glomerular filtration rate creatinine-based equation. We recommend an immediate implementation of the new Chronic Kidney Disease Epidemiology Collaboration equation (2021), which does not discriminate among any group while maintaining precision. Additionally, we recommend that Canadian laboratories and provincial kidney organizations advocate for increased testing and access to cystatin C because the combination of cystatin C and creatinine in revised equations leads to more precise estimates. Finally, we recommend that future research studies evaluating the implementation of the new equations and changes to screening, diagnosis, and management across provincial health programs be prioritized in Canada.

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.

Impaired Renal Function and Major Cardiovascular Events in Young Adults.

BACKGROUND: Cardiovascular (CV) disease in young adults (aged 18-39 years) is on the rise. Whether subclinical reductions in kidney function (ie, estimated glomerular filtration rate [eGFR] above the current threshold for chronic kidney disease but below age-expected values) are associated with elevated CV risk is unknown. OBJECTIVES: The goal of this study was to examine age-specific associations of subclinical eGFR reductions in young adults with major adverse cardiovascular events (MACEs) and MACE plus heart failure (MACE+). METHODS: A retrospective cohort study of 8.7 million individuals (3.6 million aged 18-39 years) was constructed using linked provincial health care data sets from Ontario, Canada (January 2008-March 2021). Cox models were used to examine the association of categorized eGFR (50-120 mL/min/1.73 m2) with MACE (first of CV mortality, acute coronary syndrome, and ischemic stroke) and MACE+, stratified according to age (18-39, 40-49, and 50-65 years). RESULTS: In the study cohort (mean age 41.3 years; mean eGFR 104.2 mL/min/1.73 m2; median follow-up 9.2 years), a stepwise increase in the relative risk of MACE and MACE+ was observed as early as eGFR <80 mL/min/1.73 m2 in young adults (eg, for MACE, at eGFR 70-79 mL/min/1.73 m2, ages 18-30 years: 2.37 events per 1,000 person years [HR: 1.31; 95% CI: 1.27-1.40]; ages 40-49 years: 6.26 events per 1,000 person years [HR: 1.09; 95% CI: 1.06-1.12]; ages 50-65 years: 14.9 events per 1,000 person years [HR: 1.07; 95% CI: 1.05-1.08]). Results persisted for each MACE component and in additional analyses (stratifying according to past CV disease, accounting for albuminuria at index, and using repeated eGFR measures). CONCLUSIONS: In young adults, eGFR below age-expected values were associated with an elevated risk for MACE and MACE+, warranting age-appropriate risk stratification, proactive monitoring, and timely intervention.

Pharmacological strategies to manage hyperkalaemia: out with the old, in with the new? Not so fast .

Since the 1950s, sodium polystyrene sulphonate (SPS) has been the dominant cation exchange agent prescribed for hyperkalaemia. Clinicians have had plenty of time to learn of SPS's advantages and limitations. The demands of drug regulatory agencies regarding the incorporation of medications into the market were not so stringent then as they are today, and the efficacy and safety of SPS have been questioned. In recent years, two novel cation exchangers, patiromer and sodium zirconium cyclosilicate, have received (or are in the process of receiving) regulatory approval in multiple jurisdictions globally, after scrutiny of carefully conducted trials regarding their short-term and mid-term efficacy. In this debate, we defend the view that all three agents are likely to have similar efficacy. Harms are much better understood for SPS than for newer agents, but currently there are no data to suggest that novel agents are safer than SPS. Drug choices need to consider costs, access and numbers-needed-to-treat to prevent clinically important events; for potassium exchangers, we need trials directly examining clinically important events.

Rationale and design of CONTINUITY: a Phase 4 randomized controlled trial of continued post-discharge sodium zirconium cyclosilicate treatment versus standard of care for hyperkalemia in chronic kidney disease.

Background: Individuals with chronic kidney disease (CKD) hospitalized with hyperkalemia are at risk of hyperkalemia recurrence and re-hospitalization. We present the rationale and design of CONTINUITY, a study to examine the efficacy of continuing sodium zirconium cyclosilicate (SZC)-an oral, highly selective potassium (K+) binder-compared with standard of care (SoC) on maintaining normokalemia and reducing re-hospitalization and resource utilization among participants with CKD hospitalized with hyperkalemia. Methods: This Phase 4, randomized, open-label, multicenter study will enroll adults with Stage 3b-5 CKD and/or estimated glomerular filtration rate <45 mL/min/1.73 m2, within 3 months of eligibility screening, hospitalized with a serum potassium (sK+) level of >5.0-≤6.5 mmol/L, without ongoing K+ binder treatment. The study will include an in-hospital phase, where participants receive SZC for 2-21 days, and an outpatient (post-discharge) phase. At discharge, participants with sK+ 3.5-5.0 mmol/L will be randomized (1:1) to SZC or SoC and monitored for 180 days. The primary endpoint is the occurrence of normokalemia at 180 days. Secondary outcomes include incidence and number of hospital admissions or emergency department visits both with hyperkalemia as a contributing factor, and renin-angiotensin-aldosterone system inhibitor down-titration. The safety and tolerability of SZC will be evaluated.Ethics approval has been received from all relevant ethics committees. Enrollment started March 2022 and the estimated study end date is December 2023. Conclusions: This study will assess the potential of SZC versus SoC in managing people with CKD and hyperkalemia post-discharge. Trial registration: ClinicalTrials.gov identifier: NCT05347693; EudraCT: 2021-003527-14, registered on 19 October 2021.

A Predictive Model for Kidney Failure After Nephrectomy for Localized Kidney Cancer: The Kidney Cancer Risk Equation.

RATIONALE & OBJECTIVE: Nephrectomy is the mainstay of treatment for individuals with localized kidney cancer. However, surgery can potentially result in the loss of kidney function or in kidney failure requiring dialysis/kidney transplantation. There are currently no clinical tools available to preoperatively identify which patients are at risk of kidney failure over the long term. Our study developed and validated a prediction equation for kidney failure after nephrectomy for localized kidney cancer. STUDY DESIGN: Population-level cohort study. SETTING & PARTICIPANTS: Adults (n=1,026) from Manitoba, Canada, with non-metastatic kidney cancer diagnosed between January 1, 2004, and December 31, 2016, who were treated with either a partial or radical nephrectomy and had at least 1 estimated glomerular filtration rate (eGFR) measurement before and after nephrectomy. A validation cohort included individuals in Ontario (n=12,043) with a diagnosis of localized kidney cancer between October 1, 2008, and September 30, 2018, who received a partial or radical nephrectomy and had at least 1 eGFR measurement before and after surgery. NEW PREDICTORS & ESTABLISHED PREDICTORS: Age, sex, eGFR, urinary albumin-creatinine ratio, history of diabetes mellitus, and nephrectomy type (partial/radical). OUTCOME: The primary outcome was a composite of dialysis, transplantation, or an eGFR<15mL/min/1.73m2 during the follow-up period. ANALYTICAL APPROACH: Cox proportional hazards regression models evaluated for accuracy using area under the receiver operating characteristic curve (AUC), Brier scores, calibration plots, and continuous net reclassification improvement. We also implemented decision curve analysis. Models developed in the Manitoba cohort were validated in the Ontario cohort. RESULTS: In the development cohort, 10.3% reached kidney failure after nephrectomy. The final model resulted in a 5-year area under the curve of 0.85 (95% CI, 0.78-0.92) in the development cohort and 0.86 (95% CI, 0.84-0.88) in the validation cohort. LIMITATIONS: Further external validation needed in diverse cohorts. CONCLUSIONS: Our externally validated model can be easily applied in clinical practice to inform preoperative discussions about kidney failure risk in patients facing surgical options for localized kidney cancer. PLAIN-LANGUAGE SUMMARY: Patients with localized kidney cancer often experience a lot of worry about whether their kidney function will remain stable or will decline if they choose to undergo surgery for treatment. To help patients make an informed treatment decision, we developed a simple equation that incorporates 6 easily accessible pieces of patient information to predict the risk of reaching kidney failure 5 years after kidney cancer surgery. We expect that this tool has the potential to inform patient-centered discussions tailored around individualized risk, helping ensure that patients receive the most appropriate risk-based care.

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.

Managing Hyperkalemia in the Modern Era: A Case-Based Approach.

The last decade has seen tremendous advances in the prevention and treatment of recurrent hyperkalemia. In this narrative review, we aim to highlight contemporary data on key areas in the epidemiology and management of hyperkalemia. Focusing on drug-induced hyperkalemia (the implications of renin-angiotensin-aldosterone system inhibitors [RAASi] discontinuation and the role of mineralocorticoid receptor antagonists), newer concurrent therapies that modify potassium handling (sodium-glucose transporter 2 inhibitors [SGLT2i]), the introduction of new treatment agents (oral potassium binding agents), and the controversial role of dietary potassium restriction, we apply recent research findings and review the evidence in a case-based format.

Kidney outcomes after methanol and ethylene glycol poisoning: a systematic review and meta-analysis.

INTRODUCTION: Ingestions with methanol, ethylene glycol, diethylene glycol, propylene glycol, and isopropanol are rare yet exceedingly dangerous conditions that may require emergent management with kidney replacement therapy. Little is known regarding short- and long-term kidney outcomes post-ingestion. OBJECTIVES: To comprehensively synthesize existing evidence regarding short- and long-term kidney and other outcomes of adult patients following these poisonings. METHODS: We developed a search strategy in MEDLINE via OVID and then translated it into other databases including EMBASE (via OVID), PubMed, CENTRAL (via OVID). The databases were searched from their dates of inception to 29 July 2021. A grey literature search was conducted in the International Traditional Medicine Clinical Trial Registry and ClinicalTrials.gov. All interventional and observational studies and case series with ≥ five participants that reported on the outcomes of toxic alcohol (methanol, ethylene glycol, diethylene glycol, propylene glycol and isopropanol) poisonings in adult patients ≥18 years old were included. Studies that reported mortality, kidney outcomes and/or complications attributed to toxic alcohol poisoning were eligible. RESULTS: The search strategy identified 1,221 citations. Sixty-seven studies (13 retrospective observational studies, one prospective observational study, 53 case series) met inclusion criteria (total N = 2,327 participants). No randomized controlled trials were identified per our prespecified criteria. Generally, included studies had small sample sizes (median of 27 participants) and were of low quality. Methanol and/or ethylene glycol poisoning made up 94.1% of included studies, whereas one study reported on isopropanol and none reported on propylene glycol. Results of the 13 observational studies of methanol and/or ethylene glycol poisoning were pooled for meta-analyses. The pooled in-hospital mortality estimates amongst patients with methanol and ethylene glycol poisoning were 24 and 11%, respectively. A more recent year of publication, female sex and mean age were associated with lower in-hospital mortality amongst individuals with ethylene glycol poisoning. Although hemodialysis was the most frequently employed kidney replacement therapy, the indications for initiation of this therapy were not reported in the majority of studies. At hospital discharge, kidney recovery occurred in 64.7-96.3% of patients with ethylene glycol poisoning. In studies of methanol and/or ethylene glycol poisoning, 2-3.7% of individuals required ongoing dialysis. Only one study reported post-discharge mortality. Furthermore, long-term toxic alcohol-mediated sequelae, such as visual and neurologic outcomes, were scarcely reported. DISCUSSION: Ingestions of methanol and ethylene glycol were associated with a significant short-term risk of mortality. Although a wealth of literature in the form of case reports and case series exists, high-quality evidence regarding kidney outcomes after these poisonings is lacking. We identified a paucity of standardized reporting in clinical presentations, therapeutics and outcomes amongst adults with toxic alcohol poisoning. Amongst the included studies, there was substantial heterogeneity encompassing study type, outcomes, duration of follow-up and treatment modalities. These sources of heterogeneity restricted our ability to perform comprehensive meta-analyses of all outcomes of interest. An additional limitation is the lack of studies pertaining to propylene glycol and the paucity of data on isopropanol. CONCLUSIONS: The indications for hemodialysis, long-term kidney recovery and long-term mortality risk vary widely in these poisonings and are inconsistently reported in the literature. This highlights the need for further research with standardized reporting of baseline kidney function, indications for initiation of kidney replacement therapy and short-term and long-term kidney outcomes. REGISTRATION: This systematic review protocol is registered at PROSPERO, CRD42018101955.

Development and Validation of a Predictive Risk Algorithm for Bleeding in Individuals on Long-term Hemodialysis: An International Prospective Cohort Study (BLEED-HD).

Background: Individuals with kidney disease are at a high risk of bleeding and as such tools that identify those at highest risk may aid mitigation strategies. Objective: We set out to develop and validate a prediction equation (BLEED-HD) to identify patients on maintenance hemodialysis at high risk of bleeding. Design: International prospective cohort study (development); retrospective cohort study (validation). Settings: Development: 15 countries (Dialysis Outcomes and Practice Patterns Study [DOPPS] phase 2-6 from 2002 to 2018); Validation: Ontario, Canada. Patients: Development: 53 147 patients; Validation: 19 318 patients. Measurements: Hospitalization for a bleeding event. Methods: Cox proportional hazards models. Results: Among the DOPPS cohort (mean age, 63.7 years; female, 39.7%), a bleeding event occurred in 2773 patients (5.2%, event rate 32 per 1000 person-years), with a median follow-up of 1.6 (interquartile range [IQR], 0.9-2.1) years. BLEED-HD included 6 variables: age, sex, country, previous gastrointestinal bleeding, prosthetic heart valve, and vitamin K antagonist use. The observed 3-year probability of bleeding by deciles of risk ranged from 2.2% to 10.8%. Model discrimination was low to moderate (c-statistic = 0.65) with excellent calibration (Brier score range = 0.036-0.095). Discrimination and calibration of BLEED-HD were similar in an external validation of 19 318 patients from Ontario, Canada. Compared to existing bleeding scores, BLEED-HD demonstrated better discrimination and calibration (c-statistic: HEMORRHAGE = 0.59, HAS-BLED = 0.59, and ATRIA = 0.57, c-stat difference, net reclassification index [NRI], and integrated discrimination index [IDI] all P value <.0001). Limitations: Dialysis procedure anticoagulation was not available; validation cohort was considerably older than the development cohort. Conclusion: In patients on maintenance hemodialysis, BLEED-HD is a simple risk equation that may be more applicable than existing risk tools in predicting the risk of bleeding in this high-risk population.

Contexte: Les personnes atteintes d'insuffisance rénale présentent un risque élevé d'hémorragie. Des outils permettant de déceler les personnes les plus exposées au risque pourrait aider à mettre en œuvre des stratégies d'atténuation. Objectifs: Nous avons mis au point et validé une équation prédictive (BLEED-HD) afin d'identifier les patients sous hémodialyse d'entretien qui présentent un risque élevé d'hémorragie. Type d'étude: Étude de cohorte prospective internationale (développement); étude de cohorte rétrospective (validation). Cadre: Développement: dans 15 pays (étude DOPPS phases 2 à 6 entre 2002 et 2018); validation: en Ontario (Canada). Sujets: Développement: 53 147 patients; validation: 19 318 patients. Mesures: Hospitalisation pour un événement hémorragique. Méthodologie: Modèles à risques proportionnels de Cox. Résultats: Dans la cohorte DOPPS (âge moyen: 63,7 ans; 39,7 % de femmes), 2 773 patients avaient subi un événement hémorragique (5,2 %; taux d'événements: 32 pour 1 000 années-personnes) avec un suivi médian de 1,6 an (ÉIQ: 0,9 à 2,1). BLEED-HD prend six variables en compte: âge, sexe, pays d'origine, saignement gastro-intestinal antérieur, présence d'une valve cardiaque prothétique et utilisation d'un antagoniste de la vitamine K. La probabilité observée de saignements dans les 3 ans par déciles de risque allait de 2,2 à 10,8 %. La discrimination du modèle variait de faible à modérée (statistique c: 0,65) avec un excellent étalonnage (plage de score de Brier: 0,036-0,095). La discrimination et l'étalonnage de se sont avérés semblables lors de la validation externe auprès de 19 318 patients de l'Ontario (Canada). Par rapport aux scores d'hémorragie existants, l'équation BLEED-HD a démontré une meilleure discrimination et un meilleur étalonnage (statistique c: HEMORRHAGE 0,59; HAS-BLED 0,59 et ATRIA 0,57; différence dans les c-stat, indices NRI et IDI toutes valeurs de p < 0,0001). Limites: L'information sur l'anticoagulant utilisé dans la procédure de dialyse n'était pas disponible; la cohorte de validation était beaucoup plus âgée que la cohorte de développement. Conclusion: Pour les patients sous hémodialyse d'entretien, BLEED-HD est une équation simple de calcul du risque qui peut être plus facilement applicable que les outils existants pour prédire le risque d'hémorragie dans cette population à haut risque.