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.

Social determinants of health and the transition from advanced chronic kidney disease to kidney failure.

BACKGROUND: The transition from chronic kidney disease (CKD) to kidney failure is a vulnerable time for patients, with suboptimal transitions associated with increased morbidity and mortality. Whether social determinants of health are associated with suboptimal transitions is not well understood. METHODS: This retrospective cohort study included 1070 patients with advanced CKD who were referred to the Ottawa Hospital Multi-Care Kidney Clinic and developed kidney failure (dialysis or kidney transplantation) between 2010 and 2021. Social determinant information, including education level, employment status and marital status, was collected under routine clinic protocol. Outcomes surrounding suboptimal transition included inpatient (versus outpatient) dialysis starts, pre-emptive (versus delayed) access creation and pre-emptive kidney transplantation. We examined the association between social determinants of health and suboptimal transition outcomes using multivariable logistic regression. RESULTS: The mean age and estimated glomerular filtration rate were 63 years and 18 ml/min/1.73 m2, respectively. Not having a high school degree was associated with higher odds for an inpatient dialysis start compared with having a college degree {odds ratio [OR] 1.71 [95% confidence interval (CI) 1.09-2.69]}. Unemployment was associated with higher odds for an inpatient dialysis start [OR 1.85 (95% CI 1.18-2.92)], lower odds for pre-emptive access creation [OR 0.53 (95% CI 0.34-0.82)] and lower odds for pre-emptive kidney transplantation [OR 0.48 (95% CI 0.24-0.96)] compared with active employment. Being single was associated with higher odds for an inpatient dialysis start [OR 1.44 (95% CI 1.07-1.93)] and lower odds for pre-emptive access creation [OR 0.67 (95% CI 0.50-0.89)] compared with being married. CONCLUSIONS: Social determinants of health, including education, employment and marital status, are associated with suboptimal transitions from CKD to kidney failure.

Twice versus thrice weekly hemodialysis: A systematic review.

INTRODUCTION: Thrice weekly hemodialysis (HD) is currently the norm in high income countries but there is mounting interest in twice weekly HD in certain settings. We performed this systematic review to summarize the available evidence comparing twice to thrice weekly HD. METHODS: A systematic literature search was performed in Ovid MEDLINE, Ovid Embase, and the Cochrane Central Register of Controlled Trials to identify cohort and randomized controlled trials evaluating outcomes of twice versus thrice weekly HD. The bibliographies of identified studies were hand searched to find any additional studies. Risk of bias was assessed using the Newcastle-Ottawa scale for observational studies. FINDINGS: No randomized controlled trials and 21 cohort studies were identified. Overall study quality was modest with high risk of selection bias and inadequate controlling for confounders. The most commonly evaluated outcome measures were survival and residual kidney function. No studies assessed quality of life. Study results were variable and there was no clear signal for overwhelming risk or benefit of twice versus thrice weekly HD with the exception of residual kidney function which consistently showed slower decline in the twice weekly group. DISCUSSION: There is a paucity of high quality data comparing the risks and benefits of twice vs thrice weekly HD. Randomized controlled trial evidence is required to inform clinicians and HD prescription guidelines.

Use of the FRAIL Questionnaire in Patients With End-Stage Kidney Disease.

BACKGROUND: Frailty is a clinical phenotype of decreased physiologic reserve that is associated with increased morbidity and mortality. The most meaningful way to assess frailty in patients with end-stage kidney disease (ESKD) is unknown. OBJECTIVE: To assess the prevalence of frailty in ESKD patients using the easy-to-administer FRAIL scale and, to determine its association with mortality, transplantation, and hospitalization. DESIGN: A cohort study was used. SETTING: The Ottawa Hospital, Ottawa, Ontario, Canada, was the setting of this study. PATIENTS: All eligible adult ESKD patients treated with dialysis from August to November 2017 at The Ottawa Hospital were invited to participate. MEASUREMENTS: The FRAIL scale. METHODS: Eligible patients completed an exercise survey with FRAIL questions embedded within the instrument. Number of comorbid illnesses was determined from the electronic medical record and weight loss was calculated from target weight in the patients' dialysis prescription. Mortality, transplant status, and hospitalizations were ascertained from the electronic medical record 18 months later; differences by frailty status were evaluated using descriptive statistics. Kaplan-Meier and Cox regression models were used to examine the association between frailty and transplant. RESULTS: Of 476 ESKD patients screened, 261 participated; 101 receiving peritoneal dialysis, 135 intermittent hemodialysis, and 25 home hemodialysis. Thirty-nine, 145, and 77 were frail, pre-frail, and not frail, respectively. Employment status, ethnicity, and comorbid illnesses differed significantly by frailty status, but mortality did not. In univariate analysis, frail patients were less likely to be listed for (P = .05) and to receive a kidney transplant (P = .02). However, after adjusting for age and modality, frailty was not statistically associated with a decreased likelihood of transplant (Hazard Ratio: 0.15; confidence interval [CI], 0.02-1.15; P = .068). The results were similar when accounting for the competing risk of death (P = .060). Frail patients were more likely to be hospitalized (P = .01) and spend more time in the hospital (P = .04). LIMITATIONS: Single-center design with a relatively short follow-up and small sample size limiting the number of variables that could be assessed in analysis. We also excluded patients who were unable to communicate in English or French and those patients with physical limitations such as amputations, potentially affecting generalizability. CONCLUSIONS: Frail ESKD patients as identified by the FRAIL scale are less likely to receive a renal transplant; this association diminished statistically after adjusting for age and modality and when accounting for the competing risk of death. Frail patients were at increased risk of hospitalization. Further study with larger patient numbers and longer follow-up is needed to determine the usefulness of the FRAIL scale in predicting adverse outcomes. TRIAL REGISTRATION: Not required as this was an observational study.

CONTEXTE: La fragilité est un phénotype clinique d'une réduction de la réserve physiologique et est associée à une augmentation de la morbidité et de la mortalité. La meilleure façon d'évaluer la fragilité des patients atteints d'insuffisance rénale terminale (IRT) demeure toutefois inconnue. OBJECTIFS: Mesurer la prévalence de la fragilité chez les patients atteints d'IRT à l'aide de l'échelle FRAIL et examiner les liens entre la fragilité et la mortalité, la transplantation et le nombre d'hospitalisations. TYPE D'ÉTUDE: Étude de cohorte. CADRE: L'Hôpital d'Ottawa (Ontario) au Canada. SUJETS: Tous les adultes admissibles atteints d'IRT et traités par dialyze entre août et novembre 2017 à l'Hôpital d'Ottawa ont été invités à participer à l'étude. MESURES: L'échelle FRAIL mesurant la fragilité. MÉTHODOLOGIE: Les patients admissibles ont répondu à un sondage sur l'activité physique où des questions issues de l'échelle FRAIL avaient été intégrées. Le nombre de maladies concomitantes a été obtenu à partir du dossier médical électronique et la perte de poids a été calculée à partir du poids cible figurant dans la prescription de dialyze du patient. La mortalité, le statut de la transplantation et le nombre d'hospitalisations ont été déterminés à partir du dossier médical électronique 18 mois plus tard. La statistique descriptive a servi à évaluer les différences selon l'état de fragilité. Des modèles de régression de Kaplan Meier et de Cox ont été utilisés pour examiner l'association entre la fragilité et la transplantation. RÉSULTATS: Des 476 patients atteints d'IRT dépistés, 261 ont participé à l'étude (101 traités par dialyze péritonéale, 135 par hémodialyse intermittente et 25 en hémodialyse à domicile). Ces patients ont été jugés fragiles (n=39), préfragiles (n=145) ou non fragiles (n=77). La situation d'emploi, l'ethnicité et les maladies concomitantes différaient considérablement en fonction de l'état de fragilité, mais la mortalité s'est avérée similaire. L'analyze univariée a révélé que les patients jugés fragiles étaient moins susceptibles d'être inscrits sur la liste d'attente (p=0,05) et de recevoir une greffe rénale (p=0,02). Cependant, après correction selon l'âge et la modalité de dialyze, la fragilité n'a montré aucune corrélation statistiquement significative avec une diminution de la probabilité de subir une transplantation (RR : 0,15; IC à 95 %: 0,02-1,15; p=0,068). Les résultats étaient similaires en tenant compte du risque concurrent de décès (p=0,060). Enfin, les patients jugés fragiles étaient plus susceptibles d'être hospitalisés (p=0,01), et ce, pour de plus longs séjours (p=0,04). LIMITES: Le nombre de variables pouvant être évaluées dans l'analyze est limité par le fait qu'il s'agit d'une étude monocentrique avec un suivi relativement court et portant sur un faible échantillon de patients. L'exclusion des patients incapables de communiquer en anglais ou en français et des patients présentant des limitations physiques, notamment des amputations, pourrait affecter la généralisabilité des résultats. CONCLUSION: Les patients atteints d'IRT jugés fragiles par l'échelle FRAIL sont moins susceptibles de recevoir une greffe rénale. Une réduction statistiquement significative de cette association a été observée après une correction selon l'âge et la modalité de dialyze, et en tenant compte du risque concurrent de décès. Les patients fragiles présentent également un risque accru d'être hospitalisés. Une étude plus approfondie sur une plus grande cohorte de patients et avec un suivi à plus long terme est nécessaire pour déterminer l'utilité de l'échelle FRAIL pour prédire les issues défavorables. ENREGISTREMENT DE L'ESSAI: N'est pas requis, étude observationnelle.

A case of acute pancreatitis-induced microangiopathic hemolytic anemia with thrombocytopenia.

Microangiopathic hemolytic anemia and thrombocytopenia (MAHA-T) is a rare complication of acute pancreatitis (AP). Treatment with therapeutic plasma exchange (TPE) is used at many centers. The natural history of this disease is not well understood. We report a case of acute pancreatitis induced MAHA-T with end organ dysfunction and a normal ADAMTS13 level. Following three TPEs, the patient's clinical status, blood counts and hemolytic markers stabilized. Improvement occurred even after TPE was discontinued. The optimal management of AP-induced MAHA-T is poorly understood. Many centres are reporting good outcomes with the early initiation of TPE. MAHA-T associated with acute pancreatitis is often treated with early initiation of TPE. However, the value of TPE in altering the natural history of the condition is not well understood. Further study is required to understand the role of ADAMTS13 testing to guide treatment, and the role of TPE in management.

Facility Variation and Predictors of Do Not Resuscitate Orders of Hemodialysis Patients in Canada: DOPPS.

BACKGROUND: Life expectancy in patients with end-stage kidney disease treated with hemodialysis (HD) is limited, and as such, the presence of an advanced care directive (ACD) may improve the quality of death as experienced for patients and families. Strategies to discuss and implement ACDs are limited with little being known about the status of Do Not Resuscitate (DNR) orders in the Canadian HD population. OBJECTIVES: Using data from the Dialysis Outcomes and Practice Patterns Study (DOPPS), we set out to (1) examine the variability in DNR orders across Canada and its largest province, Ontario and (2) identify clinical and functional status measures associated with a DNR order. DESIGN: We conducted a retrospective cohort study using data from the DOPPS Canada Phase 4 to 6 from 2009 to 2017. SETTING: DOPPS facilities in Canada. PATIENTS: All adults (>18 years) who initiated chronic HD with a documented ACD were included. MEASUREMENTS: ACD and DNR orders. METHODS: Descriptive statistics were compared for baseline characteristics (demographics, comorbidities, medications, facility characteristics, and patient functional status) and DNR status. The crude proportion of patients per facility with a DNR order was calculated across Canada and Ontario. Functional status was determined by activities of daily living and components of the Kidney Disease Quality of Life (KDQOL)-validated questionnaire. We used generalized estimating equations (GEEs) to create sequential multivariable models (demographics, comorbidities, and functional status) of variables associated with DNR status. RESULTS: A total of 1556 (96% of total) patients treated with HD had a documented ACD and were included. A total of 10% of patients had a DNR order. The crude variation of DNR status differed considerably across facilities within Canada, between Ontario and non-Ontario, and within Ontario (interprovince variation = 6.3%-17.1%, Ontario vs non-Ontario = 8.2% vs 11.7%, intraprovincial variation [Ontario] = 1%-26%). Patients with a DNR order were more commonly older, white, with cardiac comorbidities, with less or shorter predialysis care compared with those without a DNR order. Patients with a DNR order reported lower energy, more difficulty with transfers, meal preparation, household tasks, and financial management. In a multivariate model, age, cardiac disease, stroke, dialysis duration, and intradialytic weight gain were associated with DNR status. LIMITATIONS: Relatively small number of events or measures in certain categories. CONCLUSIONS: A large inter- and intraprovincial (Ontario) variation was observed regarding DNR orders across Canada highlighting areas for potential quality improvement. While functional status did not appear to have a bearing on the presence of a DNR order, the presence of various comorbidities was associated with the presence of a DNR order.

CONTEXTE: L'espérance de vie des patients atteints d'insuffisance rénale terminale (IRT) traités par hémodialyse (HD) est limitée et, de ce fait, la présence de directives médicales anticipées (DMA) peut améliorer la qualité du décès tel qu'il sera vécu par les patients et leurs proches. Les stratégies de discussion et de mise en œuvre de DMA sont limitées et on en sait peu sur le statut des ordonnances de non-réanimation (statut des ONR) dans la population des patients canadiens hémodialysés. OBJECTIFS: À partir des données de l'étude DOPPS (Dialysis Outcomes and Practice Patterns Study), nous avons analysé la variabilité du statut des ONR à travers le Canada et au sein de sa plus grande province, l'Ontario, puis nous avons défini des mesures des états cliniques et fonctionnels associés à une ONR. TYPE D'ÉTUDE: Étude de cohorte rétrospective. SOURCE: Les données canadiennes des phases 4 à 6 de l'étude DOPPS. PARTICIPANTS: Ont été inclus tous les adultes ayant amorcé un traitement d'HD chronique entre 2009 et 2017 et qui avaient rédigé des DMA. MESURES: La non-réanimation (statut de l'ONR) et le statut fonctionnel selon les activités de la vie quotidienne et les composantes du questionnaire validé KDQOL (Kidney Disease Quality of Life) sur la qualité de vie des personnes dialysées. MÉTHODOLOGIE: Les statistiques descriptives ont été comparées sur la base des caractéristiques à l'inclusion (données démographiques, comorbidités, médicaments, caractéristiques de l'établissement de santé et statut fonctionnel du patient) et du statut de l'ONR. La proportion brute de patients par établissement avec une ONR a été calculée pour l'ensemble du Canada et pour l'Ontario seulement. Nous avons utilisé des équations d'estimation généralisées (EEG) pour créer des modèles multivariés séquentiels (données démographiques, comorbidités et statut fonctionnel) des variables associées au statut de l'ONR. RÉSULTATS: Au total, nous avons inclus 1 556 patients hémodialysés (96 % des patients répertoriés) qui avaient des DMA documentées, et 10 % d'entre elles contenaient une ONR. La variation brute du statut de l'ONR différait considérablement d'un établissement à l'autre au Canada, entre l'Ontario et les autres provinces et entre les établissements ontariens (variation entre provinces: 6,3 à 17,1 %; Ontario par rapport aux autres provinces: 8,2 contre 11,7 %; variation intraprovinciale [Ontario]: 1 à 26 %). Les patients avec une ONR étaient généralement de race blanche et plus âgés, présentaient des comorbidités cardiaques et avaient reçu moins de soins de prédialyse et sur une plus courte durée comparativement aux patients sans ONR. Les patients ayant une ONR ont signalé des pertes d'énergie et une plus grande difficulté avec les transferts, la préparation des repas, les tâches ménagères et la gestion financière. Dans un modèle multivarié, l'âge, la maladie cardiaque, les accidents vasculaires cérébraux, la durée de la dialyse et une perte de poids intradialyse ont été associés à l'existence d'une ONR. LIMITES: Un nombre limité d'événements dans certaines catégories; les mesures de l'état fonctionnel étaient transversales. CONCLUSIONS: Une importante variation inter et intraprovinciale (Ontario) a été observée quant au statut des ONR à travers le Canada, ce qui met en évidence les domaines d'amélioration potentielle de la qualité. Bien que l'état fonctionnel du patient n'ait pas semblé avoir d'incidence sur l'existence ou non d'une ONR, on a noté une association entre la présence de comorbidités et l'existence d'une ONR.

Benefits and Barriers to and Desired Outcomes with Exercise in Patients with ESKD.

BACKGROUND AND OBJECTIVES: Patients with ESKD are sedentary. When patient-identified barriers to exercise are addressed, recruitment and retention in exercise trials remain low, suggesting that the trial design may not resonate with them. Therefore, we conducted a survey of patients on dialysis to assess perceived benefits and barriers to exercise and discover preferred outcomes and exercise type by dialysis modality and age in anticipation of designing future randomized, controlled trials. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: English- and French-speaking patients with ESKD treated with hemodialysis or peritoneal dialysis were recruited from two tertiary care hospitals in Ottawa and Montreal, Canada. Summary descriptive statistics were used to describe patient responses; then, they were separated by dialysis modality and age category. RESULTS: The survey was completed by 423 participants. Current activity levels were similar across modalities (P=0.35); 78% of younger patients walked at least 10 minutes at a time on 3 or more days compared with only 58% of older patients (P=0.001). The two most desired benefits of exercise were improved energy (18%) and strength (14%). The third priority differed, such that improved sleep, maintenance of independence, and longevity were selected by patients on peritoneal dialysis, patients on in-center hemodialysis, and patients on home hemodialysis, respectively. Older patients were most interested in improvements in energy, strength, and maintenance of independence, whereas younger patients were interested in improving energy, longevity, and transplant candidacy. Only 25% of patients were able to exercise without difficulty; the major barriers for the remaining patients were feeling patients were feeling too tired (55%), short of breath (50%), and too weak (49%). If patients were to exercise, they wanted to exercise at home (73%) using a combination of aerobic and resistance training (41%), regardless of modality or age category. CONCLUSIONS: The majority of patients undergoing maintenance dialysis in two tertiary hospitals in Ottawa and Montreal report similar desired outcomes and barriers, with greater differences by age category than modality.

Differential renal effects of candesartan at high and ultra-high doses in diabetic mice-potential role of the ACE2/AT2R/Mas axis.

High doses of Ang II receptor (AT1R) blockers (ARBs) are renoprotective in diabetes. Underlying mechanisms remain unclear. We evaluated whether high/ultra-high doses of candesartan (ARB) up-regulate angiotensin-converting enzyme 2 (ACE2)/Ang II type 2 receptor (AT2R)/Mas receptor [protective axis of the of the renin-angiotensin system (RAS)] in diabetic mice. Systolic blood pressure (SBP), albuminuria and expression/activity of RAS components were assessed in diabetic db/db and control db/+ mice treated with increasing candesartan doses (intermediate, 1 mg/kg/d; high, 5 mg/kg/d; ultra-high, 25 and 75 mg/kg/d; 4 weeks). Lower doses candesartan did not influence SBP, but ultra-high doses reduced SBP in both groups. Plasma glucose and albuminuria were increased in db/db compared with db/+ mice. In diabetic mice treated with intermediate dose candesartan, renal tubular damage and albuminuria were ameliorated and expression of ACE2, AT2R and Mas and activity of ACE2 were increased, effects associated with reduced ERK1/2 phosphorylation, decreased fibrosis and renal protection. Ultra-high doses did not influence the ACE2/AT2R/Mas axis and promoted renal injury with increased renal ERK1/2 activation and exaggerated fibronectin expression in db/db mice. Our study demonstrates dose-related effects of candesartan in diabetic nephropathy: intermediate-high dose candesartan is renoprotective, whereas ultra-high dose candesartan induces renal damage. Molecular processes associated with these effects involve differential modulation of the ACE2/AT2R/Mas axis: intermediate-high dose candesartan up-regulating RAS protective components and attenuating pro-fibrotic processes, and ultra-high doses having opposite effects. These findings suggest novel mechanisms through the protective RAS axis, whereby candesartan may ameliorate diabetic nephropathy. Our findings also highlight potential injurious renal effects of ultra-high dose candesartan in diabetes.