Immunosuppressant Medication Use in Patients with Kidney Allograft Failure: A Prospective Multicenter Canadian Cohort Study.

BACKGROUND: Patients with kidney transplant failure have a high risk of hospitalization and death due to infection. The optimal use of immunosuppressants after transplant failure remains uncertain and clinical practice varies widely. METHODS: This prospective cohort study enrolled patients within 21 days of starting dialysis after transplant failure in 16 Canadian centers. Immunosuppressant medication use, death, hospitalized infection, rejection of the failed allograft, and anti-HLA panel reactive antibodies were determined at 1, 3, 6, and 12 months and and then twice yearly until death, repeat transplantation, or loss to follow-up. RESULTS: The 269 study patients were followed for a median of 558 days. There were 33 deaths, 143 patients hospitalized for infection, and 21 rejections. Most patients (65%) continued immunosuppressants, 20% continued prednisone only, and 15% discontinued all immunosuppressants. In multivariable models, patients who continued immunosuppressants had a lower risk of death (hazard ratio [HR], 0.40; 95% confidence interval [CI], 0.17 to 0.93) and were not at increased risk of hospitalized infection (HR, 1.81; 95% CI, 0.82 to 4.0) compared with patients who discontinued all immunosuppressants or continued prednisone only. The mean class I and class II panel reactive antibodies increased from 11% to 27% and from 25% to 47%, respectively, but did not differ by immunosuppressant use. Continuation of immunosuppressants was not protective of rejection of the failed allograft (HR, 0.81; 95% CI, 0.22 to 2.94). CONCLUSIONS: Prolonged use of immunosuppressants >1 year after transplant failure was not associated with a higher risk of death or hospitalized infection but was insufficient to prevent higher anti-HLA antibodies or rejection of the failed allograft.

Glucocorticoid Minimization in Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis: An International Survey of Clinicians.

Rationale & Objective: Research in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) has focused on reducing treatment toxicities, notably through reduction of exposure to glucocorticoids. Glucocorticoid-sparing therapies such as avacopan are not widely available in many countries, and patients are exposed to high glucocorticoid doses. There is little data concerning what clinicians should accept as the lowest glucocorticoid dosing that can be used in induction therapy for AAV. Study Design: International, online survey. Setting & Participants: Clinicians in various countries with experience in managing vasculitis. Exposure and Outcomes: Survey questions to gauge interest and preferences in studying an induction of remission regimen for severe AAV using only 2 or 4 weeks of glucocorticoids without avacopan. Data collected included general opinions about standard of care for induction agents, glucocorticoids, and avacopan. Respondents were presented with 3 candidate trial designs, 2 of which proposed a combination of cyclophosphamide and rituximab induction. Analytical Approach: Using a 10-point Likert scale, respondents ranked each candidate trial on its usefulness in demonstrating whether a minimal glucocorticoid regimen would be safe and effective and their willingness to randomize into the trial. Results: There were 210 respondents to the survey. The candidate trials were rated moderate-to-high for usefulness to demonstrate safety and efficacy (scores 6-7/10), and moderate (scores 5-6/10) for willingness to randomize. Four-week glucocorticoid duration was preferred to 2 weeks, and combination cyclophosphamide-rituximab with 4-week glucocorticoids was the most preferred design. Forty-two percent of respondents felt avacopan had to be incorporated into a minimal GC trial design to want to recruit patients. Limitations: Representativeness of survey sample and generalizability of findings. Conclusions: Combination cyclophosphamide-rituximab may be the ideal way of studying minimal glucocorticoid use in severe AAV. Given its increasing uptake, incorporating avacopan into a potential trial design is important.

Research in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) has focused on using less glucocorticoids to limit side effects. New drugs that drastically limit glucocorticoid use are not available in many countries. Studies are needed to find other ways of reducing glucocorticoid exposure to treat AAV, but it is unclear how best to achieve this. We administered a survey to doctors with experience in treating AAV and had them grade different combinations of widely available treatments with 2 or 4 weeks of glucocorticoids. We found that a combination of 2 doses cyclophosphamide with 2 doses rituximab and 4 weeks of glucocorticoids was the preferred treatment. The results will guide the development of a trial studying minimal use of glucocorticoids for the treatment of AAV.

Physical Frailty and Functional Status in Patients With Advanced Chronic Kidney Disease: A Systematic Review.

Background: With an aging population and growing number of patients with chronic kidney disease (CKD), integrating the latest risk factors when deciding on a treatment plan can result in better patient care. Frailty remains a prevalent syndrome in CKD resulting in adverse health outcomes. However, measures of frailty and functional status remain excluded from clinical decision making. Objective: To examine the degree to which different measures of frailty and functional status are associated with mortality, hospitalization, and other clinical outcomes in patients with advanced CKD. Design: Systematic review. Setting: Observation studies including cohort study, case-control study, or cross-sectional study examining frailty and functional status on clinical outcomes. There were no restrictions on type of setting or country of origin. Patients: Adults with advanced CKD, including both types of dialysis patients. Measurements: Data including demographic information (e.g., sample size, follow-up time, age, country), assessments of frailty or functional status and their domains, and outcomes including mortality, hospitalization, cardiovascular events, kidney function, and composite outcomes were extracted. Methods: A search was conducted using databases Medline, Embase, and Cochrane Central Register for Controlled Trials. Studies were included from inception to March 17, 2021. The eligibility of studies was screened by 2 independent reviewers. Data were presented by instrument and clinical outcome. Point estimates and 95% confidence intervals from the fully adjusted statistical model were reported or calculated from the raw data. Results: A total of 117 unique instruments were found among 140 studies. The median sample size of studies was 319 (interquartile range, 161-893). Most studies focused on incident and chronic dialysis patient populations, with only 15% of studies examining non-dialysis CKD patients. Frailty and lower functional status were associated with an increased risk for adverse clinical outcomes such as mortality and hospitalization. The 5 individual domains of frailty were also found to be associated with poor health outcomes. Limitations: Meta-analysis could not be performed due to significant heterogeneity between studies and methods used to measure frailty and functional status. Many studies had issues with methodological rigor. Selection bias and the validity of data collection could not be ascertained for some studies. Conclusion: Frailty and functional status measures should be integrated to help guide clinical care decision making for a comprehensive assessment of risk for adverse outcomes among patients with advanced CKD. Registration PROSPERO: CRD42016045251.

Contexte: Compte tenu du vieillissement de la population et du nombre croissant de patients atteints d'insuffisance rénale chronique (IRC), l'intégration des plus récents facteurs de risque dans le processus de prise de décision d'un plan de traitement pourrait améliorer les soins aux patients. La fragilité demeure un syndrome prévalant en contexte d'IRC, qui entraîne des effets néfastes sur la santé. Pourtant, les mesures de la fragilité et de l'état fonctionnel demeurent exclues de la prise de décisions cliniques. Objectif: Déterminer à quel point les différentes mesures de la fragilité et de l'état fonctionnel sont associées à la mortalité, à l'hospitalisation et à d'autres résultats cliniques chez les patients atteints d'IRC avancée. Type d'étude: Examen systématique. Sources: Des études d'observation, y compris des études de cohorte, des études cas-témoins ou des études transversales examinant le rôle de la fragilité et de l'état fonctionnel sur les résultats cliniques. Il n'y avait pas de restrictions quant au cadre ou au pays d'origine de l'étude. Sujets: Des adultes atteints d'IRC avancée, y compris les deux types de patients sous dialyse. Mesures: Les données suivantes ont été extraites : les données démographiques (taille de l'échantillon, temps de suivi, âge des patients, pays), les évaluations de la fragilité ou de l'état fonctionnel et de leurs domaines, et les résultats cliniques (mortalité, hospitalisation, événements cardiovasculaires, fonction rénale et résultats composites). Méthodologie: Une recherche a été effectuée dans les bases de données Medline, embase et Cochrane Central Register for Controlled Trials pour répertorier les études de la création jusqu'au 17 mars 2021. L'admissibilité des études a été déterminée par deux examinateurs indépendants. Les données ont été présentées par instrument et par résultat clinique. Des estimations ponctuelles et des intervalles de confiance à 95 % du modèle statistique ajusté ont été rapportés ou calculés à partir des données brutes. Résultats: Parmi les 140 études répertoriées, 117 instruments uniques ont été trouvés. La taille médiane des échantillons était de 319 patients (ÉIQ : 161 à 893). La plupart des études portaient sur des populations de patients incidents et sous dialyse chronique, seulement 15 % des études portaient sur des patients atteints d'IRC non dialysés. La fragilité et un faible état fonctionnel ont été associés à un risque accru de résultats cliniques défavorables comme une hospitalisation ou le décès. Les cinq domaines individuels de la fragilité ont également été associés à de mauvais résultats de santé. Limites: L'hétérogénéité significative entre les études et les méthodes utilisées pour mesurer la fragilité et l'état fonctionnel ne permettait pas de procéder à une méta-analyse. De nombreuses études n'étaient pas rigoureuses sur le plan méthodologique. Les biais de sélection et la validité de la collecte des données n'ont pas pu être vérifiés pour certaines études. Conclusion: Les mesures de la fragilité et de l'état fonctionnel devraient être intégrées au processus de prise de décision afin d'orienter les soins cliniques et de permettre une évaluation complète du risque d'effets indésirables chez les patients atteints d'IRC avancée. Enregistrement PROSPERO: CRD42016045251.

Eating disorders in biological males: clinical presentation and consideration of sex differences in a pediatric sample.

BACKGROUND: The growing body of research on eating disorders among male adolescents reveals some sex differences in clinical presentation. The current study set out to replicate and extend recent research on the clinical and medical characteristics of male youth with eating disorders, and examine sex differences between biological males and females in a tertiary pediatric eating disorder treatment setting. METHODS: A retrospective chart review was conducted with all biological males who were admitted to the Eating Disorders Programs at British Columbia Children's Hospital (2003-2015) or the Looking Glass Residence (2011-2015). Clinical data, including demographics, percentage of median body mass index (% mBMI), and psychiatric diagnoses, were recorded along with medical data (i.e., vital signs, basic biochemistry investigations, and bone mineral density). A comparison group of females with eating disorders who received treatment at British Columbia Children's Hospital in the inpatient or outpatient streams (2010-2015) were included, to examine sex differences with males who were admitted during the same period. RESULTS: A total of 71 male youth were included in the chart review. Males had significant medical complications, with 26.5% of the sample presenting with a heart rate of less than 50 beats per minute and 31.4% presenting with a bone mineral density z-score for the lumbar spine ≤ - 1. Sex differences between the subset of males who were treated between 2010 and 2015 (n = 41) and the females (n = 251) were examined. Females were more likely than were males to have a diagnosis of anorexia nervosa or bulimia nervosa, and to be underweight (< 95% mBMI) at admission. Males were younger than females, but no differences emerged in the duration of the eating disorder symptoms. No sex differences emerged relating to medical instability (e.g., bradycardia). CONCLUSIONS: A large proportion of male children and youth with eating disorders are medically compromised at admission. Males were younger than females, and were less likely than females to have a diagnosis of anorexia nervosa or bulimia nervosa. Males who were underweight at admission had also lost a lower percentage of body weight in comparison to females. The current study replicates previous sex differences reported in pediatric samples.