Pleural procedures: an audit of practice and complications in a regional Australian teaching hospital.

BACKGROUND: Pleural procedures are essential for the investigation and management of pleural disease and can be associated with significant morbidity and mortality. There is a lack of pleural procedure complication data in the Australian and New Zealand region. AIMS: To review pleural procedure practices at Wollongong Hospital with an emphasis on the assessment of complications, use of thoracic ultrasound (TUS), pathology results and comparison of findings with international data. METHODS: Retrospective analysis of medical records was performed on pleural procedures identified through respiratory specialist trainee logbooks at Wollongong Hospital from January 2018 to December 2021. Comparison of complication rates was made to the British Thoracic Society 2011 a national pleural audit. RESULTS: One hundred and twenty-one pleural procedures were identified. There were 71 chest drains, 49 thoracocentesis and one indwelling pleural catheter (IPC) insertion. Ninety-seven per cent of procedures were performed for pleural effusions and 3% for pneumothorax. This audit demonstrated a complication rate (excluding pain) of 16.9% for chest drains and 4.1% for thoracocentesis. This gave an overall complication event rate of 10.8% (excluding pain) for pleural procedures. There was no major bleeding, organ puncture, pleural space infection or death. Bedside TUS was used in 99% of procedures. CONCLUSION: Complication rates for pleural procedures performed by respiratory specialist trainees at Wollongong Hospital are comparable with international outcomes. This audit provides data for comparison on pleural procedure complication rates in Australia. Future studies are required to determine complication rates with IPCs.

Multidisciplinary Support To Access living donor Kidney Transplant (MuST AKT): A Clinical Research Protocol for a Pilot Randomized Controlled Trial to Increase Living Kidney Donation.

Background: Living donor kidney transplantation (LDKT) is the optimal treatment for eligible patients with kidney failure, although it is underutilized. Contextually tailored patient- and family-centered interventions may be effective to increase LDKT. Objective: We outline a protocol to test the feasibility of the Multidisciplinary Support To Access living donor Kidney Transplant (MuST AKT) intervention designed to increase LDKT. Design: Non-blinded single-center pilot randomized controlled trial with a qualitative interview component. Setting: Academic transplant referral center in Northern Alberta Region with a population of more than 2 million in its catchment area. Patients: English-speaking patients of the age range 18 to 75 years who are referred for kidney transplantation are eligible to participate. Measurements: Feasibility will be assessed by indicators of recruitment, retention, and completion rates, treatment fidelity, adherence to intervention, engagement in intervention, and acceptability. Methods: Participants will be randomly assigned 1:1 to either standard care (control) or the experimental group who receive standard care plus the MuST AKT intervention, a person-centered program designed to assist and enable the kidney transplant candidate to achieve what is required to receive an LDKT. The intervention consists of an introductory session and 4 intervention sessions delivered in-person or virtually. Limitations: Inferences cannot be drawn regarding the efficacy/effectiveness of the MuST AKT intervention. This study is non-blinded. Conclusions: This pilot study is the first step in our broader initiative to increase LDKT in our health care jurisdiction. The results of this study will be used to inform the development of a future definitive randomized controlled trial. Trial registration number: NCT04666545.

Contexte: Bien qu'elle soit encore sous-utilisée, la transplantation d'un rein provenant d'un donneur vivant (TRDV) constitue le traitement optimal pour les patients atteints d'insuffisance rénale qui sont admissibles. Des interventions personnalisées, axées sur le patient et la famille, pourraient s'avérer efficaces pour favoriser la TRDV. Objectif: Nous décrivons un protocole examinant la faisabilité de l'intervention MuST AKT (Multidisciplinary Support To Access living donor Kidney Transplant), laquelle vise l'augmentation des TRDV. Conception: Essai clinique pilote unicentrique, sans insu, comportant une composante d'entretiens qualitatifs. Cadre: Un center universitaire pour les transplantations du Nord de l'Alberta, situé dans une zone de référence comptant plus de deux millions de personnes. Sujets: Seront admissibles tous les patients anglophones âgés de 18 à 75 ans aiguillés pour une transplantation rénale. Mesures: La faisabilité sera évaluée par des indicateurs du taux de recrutement, de rétention et d'achèvement, de même que par la fidélité au traitement, l'adhésion à l'intervention, l'engagement dans l'intervention et l'acceptabilité. Méthodologie: Les sujets seront répartis aléatoirement 1:1 dans le groupe témoin, qui recevra les soins habituels, ou dans le groupe expérimental, qui recevra les soins habituels et l'intervention MuST AKT. Ce program axé sur le patient est conçu pour aider les candidats à une greffe rénale à réaliser les étapes nécessaires pour recevoir une TRDV. L'intervention est constituée d'une séance d'introduction et de quatre séances d'intervention réalisées en personne ou virtuellement. Limites: Nous ne serons pas en mesure de tirer des conclusions quant à l'efficacité de l'intervention MuST AKT. Cette étude n'est pas menée en aveugle. Conclusion: Cette étude pilote constitue la première étape d'une initiative plus vaste qui vise à accroître la TRDV dans notre région sanitaire. Les résultats de cette étude seront utilisés pour guider l'élaboration d'un futur essai clinique définitif.

Micro- and Nanoplastics Breach the Blood-Brain Barrier (BBB): Biomolecular Corona's Role Revealed.

Humans are continuously exposed to polymeric materials such as in textiles, car tires and packaging. Unfortunately, their break down products pollute our environment, leading to widespread contamination with micro- and nanoplastics (MNPs). The blood-brain barrier (BBB) is an important biological barrier that protects the brain from harmful substances. In our study we performed short term uptake studies in mice with orally administered polystyrene micro-/nanoparticles (9.55 µm, 1.14 µm, 0.293 µm). We show that nanometer sized particles-but not bigger particles-reach the brain within only 2 h after gavage. To understand the transport mechanism, we performed coarse-grained molecular dynamics simulations on the interaction of DOPC bilayers with a polystyrene nanoparticle in the presence and absence of various coronae. We found that the composition of the biomolecular corona surrounding the plastic particles was critical for passage through the BBB. Cholesterol molecules enhanced the uptake of these contaminants into the membrane of the BBB, whereas the protein model inhibited it. These opposing effects could explain the passive transport of the particles into the brain.

Tramadol as a patient-initiated component of multimodal pain management: a pilot study of 364 lower limb arthroplasty cases.

BACKGROUND: Multimodal therapy (MMT) for analgesia following joint arthroplasty continues to reduce cost and the requirement of strong opioids post-operatively. Tramadol immediate release is an important MMT component providing synergistic pain relief via dual µ-opioid agonism and serotonin and noradrenaline reuptake inhibition. Case reports have shown tramadol when combined with antidepressants cause serotonin syndrome, but this has yet to be demonstrated in larger studies. We undertook a pilot study assessing the functional outcomes and incidence of side effects associated with tramadol in lower limb arthroplasty patients with a focus on those taking concomitant antidepressants. METHODS: Primary and revision hip and knee arthroplasties performed in 2018-2019 by a senior surgeon were included (n = 364). Patient records were assessed to determine pain scores, length of hospitalization, prescription of tramadol and antidepressants, self-reported side effects and previous adverse reactions associated with tramadol. RESULTS: Nine-five percentage of patients had been prescribed tramadol, and 16% had concurrent prescription of tramadol and one or more antidepressants. The total rate of adverse effects associated with tramadol before and during the study was 7% (n = 25) including two cases of concomitant tramadol and antidepressant use. For patients on tramadol, median 2-week post-operative pain score was 1.5 (IQR 1-2.5) out of 10 and hospitalization length was 1 (IQR 1-2) days. CONCLUSION: Tramadol immediate release appears to be well tolerated among our patient population with no significantly increased prevalence of side effects when co-administered with low and moderate dose antidepressants.

Targeting Alzheimer's Disease: The Critical Crosstalk between the Liver and Brain.

Alzheimer's disease (AD), an age-related neurodegenerative disorder, is currently incurable. Imbalanced amyloid-beta (Aß) generation and clearance are thought to play a pivotal role in the pathogenesis of AD. Historically, strategies targeting Aß clearance have typically focused on central clearance, but with limited clinical success. Recently, the contribution of peripheral systems, particularly the liver, to Aß clearance has sparked an increased interest. In addition, AD presents pathological features similar to those of metabolic syndrome, and the critical involvement of brain energy metabolic disturbances in this disease has been recognized. More importantly, the liver may be a key regulator in these abnormalities, far beyond our past understanding. Here, we review recent animal and clinical findings indicating that liver dysfunction represents an early event in AD pathophysiology. We further propose that compromised peripheral Aß clearance by the liver and aberrant hepatic physiological processes may contribute to AD neurodegeneration. The role of a hepatic synthesis product, fibroblast growth factor 21 (FGF21), in the management of AD is also discussed. A deeper understanding of the communication between the liver and brain may lead to new opportunities for the early diagnosis and treatment of AD.

Designing an App for Immunosuppression Adherence and Communication: A Qualitative Approach.

BACKGROUND: Immunosuppression nonadherence may be the most important factor limiting long-term allograft survival. OBJECTIVE: Following user-centered design, we explored the essential priorities and preferences of kidney transplant recipients and healthcare providers (HCP) to inform development of a smartphone app to improve immunosuppression adherence and communication. DESIGN: A qualitative descriptive research design was used. SETTING: The University of Alberta Hospital adult kidney transplant program in Edmonton, Canada. PARTICIPANTS: Participants were recruited by convenience sampling and included 32 kidney transplant recipients and 11 HCPs. METHODS: Seven focus groups (5 with recipients and 2 with HCPs) were conducted to inform app development. Sessions were recorded, and transcripts were coded to elucidate themes. RESULTS: App development to improve adherence was not a priority for HCP. Recipients prioritized choice: that all features be optional. Recipients preferred support while traveling; access to laboratory results; and use by younger or newly transplanted recipients. Both recipients and HCP preferred linkage to pharmacy; and self-management and accountability.For the app to improve communication, HCPs believed the priorities to be addressed included: clarity on scope of app; legal, ethical, and professional obligations; and charting. Both recipients and HCP prioritized HCP workload, and broader medication and health concerns. Healthcare providers preferred tech support; both recipients and HCPs preferred app access for nontransplant HCP. LIMITATIONS: Limitations include underrepresentation of physicians, recipients with racial/ethnic diversity, and potential selection bias of transplant recipients who perceived themselves to be adhering to immunosuppression medications. CONCLUSION: Future research is needed for the app to become a comprehensive, secure platform for broader communication between recipients and HCP, pharmacies, and nontransplant clinicians while streamlining HCP workload.

CONTEXTE: La non-observance du traitement immunosuppresseur pourrait s'avérer le facteur limitant ayant la plus grande incidence sur la survie à long terme de l'allogreffe. OBJECTIFS: Suivant une conception centrée sur l'utilisateur, nous avons exploré les préférences et les priorités essentielles des receveurs d'une greffe rénale et des fournisseurs de soins de santé (FSS) afin d'orienter le développement d'une application pour téléphones intelligents visant à améliorer les communications et l'observance du traitement immunosuppresseur. TYPE D'ÉTUDE: Un plan de recherche qualitatif et descriptif a été utilisé. CADRE: Le program de transplantation rénale pour adultes du University of Alberta Hospital à Edmonton (Canada). PARTICIPANTS: Les participants ont été recrutés par échantillonnage de commodité. L'étude a inclus 32 receveurs d'une greffe rénale et 11 FSS. MÉTHODOLOGIE: Sept groupes de discussion (5 avec les receveurs, 2 avec les FSS) ont été organisés pour guider le développement de l'application. Les séances ont été enregistrées et les transcriptions ont été codées afin de préciser les thèmes. RÉSULTATS: Le développement d'une application pour améliorer l'observance au traitement n'était pas une priorité pour les FSS. Les receveurs d'une greffe priorisaient d'avoir le choix : ils souhaitaient que toutes les fonctionnalités soient facultatives. Les receveurs d'une greffe avaient une préférence pour une application qui offrirait du soutien lors de leurs déplacements, qui permettrait un accès aux résultats de laboratoire et qui soit utilisée par les nouveaux greffés et les receveurs plus jeunes. Tous les participants préféraient que l'application propose un lien vers la pharmacie et qu'elle favorise l'autogestion et la responsabilisation.Pour que l'application améliore la communication, les FSS étaient d'avis qu'il fallait s'attarder aux priorités suivantes : la clarté de la portée de l'application; les obligations juridiques, éthiques et professionnelles; et la tenue des dossiers. Tant les receveurs d'une greffe que les FSS accordaient une priorité à la charge de travail des professionnels de la santé et aux préoccupations plus générales en matière de santé et de médicaments. Les FSS préféraient une assistance technique; et tous les participants avaient une préférence pour que l'application soit accessible aux FSS ne travaillant pas en transplantation. LIMITES: Parmi les limites figurent la sous-représentation des médecins, l'absence de receveurs issus de la diversité raciale/ethnique et un possible biais de sélection des receveurs d'une greffe qui se perçoivent comme adhérant à leur traitement immunosuppresseur. CONCLUSION: D'autres recherches sont nécessaires pour que l'application devienne une plateforme complète et sécurisée qui facilite la communication entre les patients, les professionnels de la santé, les pharmacies et les cliniciens ne travaillant pas en transplantation, tout en allégeant la charge de travail des fournisseurs de soins.

Global Estimates of Capacity for Kidney Transplantation in World Countries and Regions.

BACKGROUND: Kidney transplantation (KT) is the optimal treatment for kidney failure and is associated with better quality of life and survival relative to dialysis. However, knowledge of the current capacity of countries to deliver KT is limited. This study reports on findings from the 2018 International Society of Nephrology Global Kidney Health Atlas survey, specifically addressing the availability, accessibility, and quality of KT across countries and regions. METHODS: Data were collected from published online sources, and a survey was administered online to key stakeholders. All country-level data were analyzed by International Society of Nephrology region and World Bank income classification. RESULTS: Data were collected via a survey in 182 countries, of which 155 answered questions pertaining to KT. Of these, 74% stated that KT was available, with a median incidence of 14 per million population (range: 0.04-70) and median prevalence of 255 per million population (range: 3-693). Accessibility of KT varied widely; even within high-income countries, it was disproportionately lower for ethnic minorities. Universal health coverage of all KT treatment costs was available in 31%, and 57% had a KT registry. CONCLUSIONS: There are substantial variations in KT incidence, prevalence, availability, accessibility, and quality worldwide, with the lowest rates evident in low- and lower-middle income countries. Understanding these disparities will inform efforts to increase awareness and the adoption of practices that will ensure high-quality KT care is provided around the world.

Gene Expression Profiling in Kidney Transplants with Immune Checkpoint Inhibitor-Associated Adverse Events.

BACKGROUND AND OBJECTIVES: Immune checkpoint inhibitors are increasingly used to treat various malignancies, but their application in patients with kidney transplants is complicated by high allograft rejection rates. Immune checkpoint inhibitor-associated rejection is a novel, poorly understood entity demonstrating overlapping histopathologic features with immune checkpoint inhibitor-associated acute interstitial nephritis, which poses a challenge for diagnosis and clinical management. We sought to improve the understanding of these entities through biopsy-based gene expression analysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: NanoString was used to measure and compare the expression of 725 immune-related genes in 75 archival kidney biopsies, including a 25-sample discovery cohort comprising pure T cell-mediated rejection and immune checkpoint inhibitor-associated acute interstitial nephritis and an independent 50-sample validation cohort comprising immune checkpoint inhibitor-associated acute interstitial nephritis, immune checkpoint inhibitor-associated T cell-mediated rejection, immune checkpoint inhibitor-associated crescentic GN, drug-induced acute interstitial nephritis, BK virus nephropathy, and normal biopsies. RESULTS: Significant molecular overlap was observed between immune checkpoint inhibitor-associated acute interstitial nephritis and T cell-mediated rejection. Nevertheless, IFI27, an IFN-α-induced transcript, was identified and validated as a novel biomarker for differentiating immune checkpoint inhibitor-associated T cell-mediated rejection from immune checkpoint inhibitor-associated acute interstitial nephritis (validation cohort: P<0.001, area under the receiver operating characteristic curve =100%, accuracy =86%). Principal component analysis revealed heterogeneity in inflammatory gene expression patterns within sample groups; however, immune checkpoint inhibitor-associated T cell-mediated rejection and immune checkpoint inhibitor-associated acute interstitial nephritis both demonstrated relatively more molecular overlap with drug-induced acute interstitial nephritis than T cell-mediated rejection, suggesting potential dominance of hypersensitivity mechanisms in these entities. CONCLUSIONS: These results indicate that, although there is significant molecular similarity between immune checkpoint inhibitor-associated rejection and acute interstitial nephritis, biopsy-based measurement of IFI27 gene expression represents a potential biomarker for differentiating these entities.

Reduced myocardial blood flow reserve in kidney transplant candidates may hamper risk stratification.

BACKGROUND: Vasodilator nuclear stress testing is frequently ordered for risk stratification prior to kidney transplantation. Since 82Rb-positron emission tomography-computed tomography can measure myocardial blood flow (MBF), the response to vasodilator stress can be verified rendering the results of the scan more reliable. METHODS: We reviewed the MBF response to dipyridamole infusion in 328 patients with end-stage kidney disease (ESKD) prior to transplant (188 hemodialysis-HD, 120 peritoneal dialysis-PD, and 20 pre-dialysis patients-CKD5) and in 100 controls with normal kidney function. A stress/rest MBF ratio ≥ 2 was considered an adequate response to dipyridamole. Coronary artery calcium (CAC) was measured on CT. RESULTS: Inadequate MBF response was seen in 36%-HD, 21%-PD, 45%-CKD5 vs. 23%-controls (p = 0.006). Univariable predictors of poor MBF response in ESKD patients were age, diabetes mellitus, and CAC (all p < 0.03) while serum hemoglobin was borderline significant (p = 0.052). Multivariable predictors of a poor MBF response were age (p = 0.002) and lower serum hemoglobin (p = 0.014). Ischemia was identified in 8% of ESKD patients and 24% of controls (p < 0.001). CONCLUSIONS: ESKD patients are less likely to respond appropriately to vasodilator stress compared to patients with normal renal function and had a lower incidence of ischemia despite a high pre-test probability of disease. Physicians performing vasodilator stress without MBF measurement should be aware of the high probability of a false negative response.

Incidence, Risk Factors, and Outcomes of Kidney Transplant Recipients Treated With Both Basiliximab and Antithymocyte Globulin.

BACKGROUND: Kidney transplant recipients are given induction therapy to rapidly reduce the immune response and prevent rejection. Guidelines recommend that an interleukin-2 receptor antibody (basiliximab) be the first-line agent and that a lymphocyte-depleting agent (antithymocyte globulin [ATG]) be reserved for those at high immunologic risk. OBJECTIVE: To determine the incidence, risk factors, and outcomes for patients who receive both basiliximab and ATG for induction compared to either agent alone. DESIGN: Retrospective cohort study. SETTING: We used the transplant electronic medical record at the University of Alberta Hospital in Edmonton, Canada. PATIENTS/SAMPLES/PARTICIPANTS: We included incident adult kidney transplant recipients from 2013 to 2018. MEASUREMENTS: We measured baseline characteristics, type, and dose of induction therapy used, estimated glomerular filtration rate (eGFR) at 1-year posttransplant, and outcomes of all-cause graft failure, death-censored graft failure, all-cause mortality, and death with a functioning graft. METHODS: Differences between induction groups were compared using chi-square test for categorical variables and Kruskal-Wallis tests for continuous variables. We performed multivariable logistic regression modeling with type of induction therapy as the dependent variable and the case-level factors as the predictors (adjusted odds ratio). We estimated the Kaplan-Meier failure functions and used log-rank tests to assess statistical significance of differences in unadjusted incidence across induction therapy types. We compared cumulative incidence functions using a Fine and Gray competing risk regression model. RESULTS: In all, 430 kidney transplant recipients were followed for a mean of 3.9 years (standard deviation 1.5). Of these, 71% (n = 305) received basiliximab alone, 22% (n = 93) received ATG alone, and 7% (n = 32) received both basiliximab and ATG. After adjusting for age and sex, compared to the basiliximab alone group, patients were more likely to receive dual-induction therapy if they were sensitized (calculated panel reactive antibody ≥80%), had diabetes mellitus or peripheral vascular disease, or experienced delayed graft function. Compared to the ATG alone group, the dual-induction therapy group had worse graft function at 1 year (mean eGFR 42 vs. 59 mL/min/1.73 m2, P = .0008) and an increased risk of all-cause graft failure (31% vs. 13%, P = .02) and death-censored graft failure (16% vs. 4%, P = .03). LIMITATIONS: There is a risk of confounding by indication, as patients who received dual-induction therapy likely had worse outcomes due to the indication for dual-induction therapy (such as delayed graft function). CONCLUSIONS: In our study, 1 out of 10 recipients who were treated with basiliximab also received ATG for induction therapy. These patients experienced worse outcomes than those treated with ATG alone. TRIAL REGISTRATION: Not applicable (cohort study).

CONTEXTE: Les receveurs d'une greffe rénale reçoivent un traitement par induction pour réduire la réponse immunitaire et prévenir le rejet. Les lignes directrices recommandent qu'un anticorps du récepteur de l'interleukine-2 (basiliximab) soit l'agent de première ligne et qu'un agent de déplétion immunitaire (immunoglobulines anti-thymocytes [ATG]) soit réservé aux patients présentant un risque immunologique élevé. OBJECTIF: Connaître l'incidence d'une double induction (basiliximab + ATG), les facteurs de risque et l'issue des patients l'ayant reçue comparativement aux patients n'ayant reçu qu'un seul des deux agents. TYPE D'ÉTUDE: Étude de cohorte rétrospective. CADRE: Nous avons consulté les dossiers médicaux électroniques de transplantation du University of Alberta Hospital d'Edmonton (Canada). SUJETS: Ont été inclus les adultes receveurs d'une greffe rénale entre 2013 et 2018. MESURES: Nous avons mesuré les caractéristiques démographiques initiales, le type et la dose du traitement d'induction administré, le débit de filtration glomérulaire estimé (DFGe) mesuré un an post-greffe, de même que les résultats cliniques de dysfonction du greffon de toutes causes, de dysfonction du greffon censurée par le décès, de mortalité toutes causes ou de décès avec un greffon fonctionnel. MÉTHODOLOGIE: Les différences entre les groupes d'induction ont été comparées à l'aide du test de Chi-Deux (variables catégorielles) et des tests de Kruskal-Wallis (variables continues). Nous avons procédé à une modélisation de régression logistique multivariable avec le type de traitement d'induction comme variable dépendante et les facteurs de risque pour chaque cas comme prédicteurs (rapport de cote corrigé). Nous avons évalué les défaillances de fonction avec une courbe de Kaplan-Meier, et des tests logarithmiques par rangs ont été employés pour évaluer la signification statistique des différences dans l'incidence non corrigée entre les types de traitements d'induction administrés. Un modèle de régression des risques concurrents Fine and Gray a été employé pour comparer les fonctions d'incidence cumulée. RÉSULTATS: En tout, 430 receveurs d'une greffe rénale ont été suivis sur une période moyenne de 3,9 ans (écart type: 1,5 an). De ceux-ci, 71 % (n = 305) n'avaient reçu que du basiliximab, 22 % (n = 93) n'avaient reçu que des ATG et 7 % (n = 32) avaient reçu le double traitement par induction. Après la correction pour l'âge et le sexe, et lorsque comparés aux patients n'ayant reçu que du basiliximab, les patients sensibilisés (allo-anticorps calculés d'au moins 80 %), diabétiques, atteints de maladie vasculaire périphérique ou ayant vécu un délai dans la reprise de la fonction du greffon se sont avérés plus susceptibles de recevoir le double traitement par induction. Le groupe ayant reçu le double traitement par induction présentait une moins bonne fonction du greffon un an après l'intervention (DFGe moyen: 42 vs 59 ml/min/1,73 m2; P = .0008), avaient un risque accru de dysfonction du greffon toutes causes (31 % vs 13 %; P =.02) et un taux de dysfonction du greffon censurée par le décès plus élevé (16 % vs 4 %; P = .03) lorsque comparé au groupe traité par les ATG seulement. LIMITES: Un risque de confusion par indication existe puisque les patients ayant reçu le double traitement par induction ont probablement eu de moins bons résultats, notamment un retard dans la reprise de la fonction du greffon, en raison de cette indication. CONCLUSION: Dans notre étude, un patient sur dix avait reçu le double traitement par induction (basiliximab et ATG). Ces patients ont cependant eu de moins bons résultats de santé que les patients traités aux ATG seulement. ENREGISTREMENT DE L'ESSAI: Sans objet (étude de cohorte).

Prevalence and Correlates of Accelerometer-Based Physical Activity and Sedentary Time Among Kidney Transplant Recipients.

BACKGROUND: Physical activity is recommended for kidney transplant recipents as it may improve outcomes including mortality, exercise capacity, muscle strength, and health-related quality of life. OBJECTIVE: The objective of this study was to examine accelerometer-based physical activity and sedentary time profiles among kidney transplant recipients and examine possible demographic and clinical correlates of physical activity and sedentary time. DESIGN: Cross-sectional. SETTING: Edmonton, Alberta, Canada. PATIENTS: Kidney transplant recipients were recruited (N = 1,284) from the Northern Alberta Renal Program's Nephrology Information System database (1993-2016). MEASUREMENTS: Participants wore an ActiGraph GT3X+ accelerometer on their hip during waking hours for seven consecutive days. METHODS: Kidney transplant recipients (1993-2016) recruited from the Northern Alberta Renal Program's Nephrology Information System database wore an accelerometer and completed a self-reported questionnaire. Multiple linear regression was used to determine associations between activity level, demographic, and clinical characteristics. RESULTS: Participants' (n = 133; 11% response rate) mean age (SD) was 58 (14) years and 56% were female. Mean total sedentary time was 9.4 (1.4) hours per day; total moderate-to-vigorous physical activity (MVPA) time was 20.7 (19.6) minutes per day. MVPA was significantly associated with age where each additional year was associated with 0.48 fewer min/day (ie, ~30 seconds) (unstandardized beta: B = -0.48 min/day, 95% confidence interval [95% CI]: -0.75, -0.22). Sedentary time was significantly associated with age (B = 1.0 min/day, 95% CI: 0.03, 1.9), body mass index (B = 2.7 min/day, 95% CI: 0.2, 5.13), education (B = 39.1 min/day, 95% CI: 12.3, -65.8), and inversely associated with income (B = -44.9 min/day, 95% CI: -73.1, -16.8). LIMITATIONS: Limitations include the cross-sectional design, poor response rate, and limited generalizability of the results. CONCLUSIONS: Kidney transplant recipients showed high volumes of sedentary time and low volumes of health-enhancing physical activity. Understanding correlates of these behaviors may aid in the development of interventions to favorably change these behaviors.

CONTEXTE: L'activité physique est recommandée aux receveurs d'une greffe rénale puisqu'elle peut améliorer leur santé ­ augmentation de la tolérance à l'effort, de la force musculaire et de la qualité de vie liée à l'état de santé ­ et limiter les issues indésirables, notamment la mortalité. OBJECTIF: L'objectif était double: caractériser l'activité physique et le profil de sédentarité des receveurs d'une greffe rénale avec un accéléromètre, et analyser les possibles corrélations démographiques et cliniques de l'activité physique et du comportement sédentaire. TYPE D'ÉTUDE: Étude transversale. CADRE: Edmonton, en Alberta (Canada). SUJETS: Des patients ayant reçu une greffe rénale entre 1993 et 2016 (n = 1284) et recrutés dans la base de données du système d'information en néphrologie du Northern Alberta Renal Program (NARP). MESURES: Les participants portaient un accéléromètre Actigraph GT3X+ à la hanche durant les heures d'éveil pour sept jours consécutifs. MÉTHODOLOGIE: Les receveurs d'une greffe rénale (1993 à 2016) recrutés dans la base de données du système d'information en néphrologie du NARP ont porté un accéléromètre et rempli un questionnaire d'auto-déclaration. Une régression linéaire multiple a été employée pour établir les associations entre le niveau d'activité physique et les données démographiques et cliniques des patients. RÉSULTATS: Les participants (n = 133; taux de réponse de 11 %), dont 56 % étaient des femmes, étaient âgés de 58 ans en moyenne (écart-type [É-T]: 14 ans). La période de sédentarité s'élevait en moyenne à 9,4 heures par jour (É-T: 1,4 heure), alors que la période moyenne d'activité physique modérée à vigoureuse (APMV) s'établissait à 20,7 minutes par jour (É-T: 19,6 minutes). L'APMV a été associée de façon significative à l'âge du patient, où chaque année additionnelle en âge a correspondu à une réduction de 0,48 minute par jour (environ 30 sec.) de l'APMV (bêta non normalisé [ß] = -0,48 min/jour; 95% IC: -0,75 à -0,22). Les comportements sédentaires ont été associés de façon significative à l'âge (ß = 1,0 min/jour, 95% IC: 0,03 à 1,9), à l'IMC (ß = 2,7 min/jour, 95% IC: 0,2 à 5,13), au niveau de scolarité (ß = 39,1 min/jour, 95% IC: 12,3 à -65,8), et inversement associés au revenu du patient (ß = -44,9 min/jour, 95% IC: -73,1 à -16,8). LIMITES: La généralisation des résultats est limitée par la nature transversale de l'étude et par le faible taux de réponse. CONCLUSION: Les receveurs d'une greffe rénale sont largement sédentaires et pratiquent peu d'activité physique ayant un effet bénéfique sur leur santé. La compréhension des corrélations de ces comportements pourrait faciliter le développement d'interventions visant à les modifier favorablement.

Acute Kidney Injury in Pregnant Patient With Pancreas-Kidney Transplant Caused by Abdominal Compartment Syndrome: A Case Presentation, Review of Literature, and Proposal of Diagnostic Approach.

RATIONALE: With increasing number of complex medical patients with renal transplant who get pregnant, clinicians need to be aware of abdominal compartment syndrome which may masquerade as acute renal allograft injury in pregnancy. PRESENTING CONCERNS OF THE PATIENT: A 34-year-old nulliparous Caucasian female with end-stage renal disease (ESRD) due to type 1 diabetes mellitus who received a simultaneous pancreas-kidney transplant (SPK) in 2006 and then after rejection of renal allograft another, kidney-only allograft from a donation after circulatory death became pregnant in May 2013 with dichorionic, diamniotic twins without reproductive technology, and during pregnancy, she developed two episodes of acute injury to the renal allograft. DIAGNOSES: End-stage renal disease secondary to type I diabetes, acute renal allograft injury, tacrolimus toxicity, abdominal pain. INTERVENTIONS INCLUDING PREVENTION AND LIFESTYLE: She received intravenous hydration, medications contributing to renal failure were held, and pain and nauseas were controlled appropriately. Abdominal compartment syndrome was managed by maintaining intravascular pressure and optimizing regional and systemic vascular perfusion by appropriate fluid balance, evacuating intraluminal contents by decompressing gastrointestinal system, and improving abdominal wall compliance by using appropriate analgesics, sedation, and patient positioning. OUTCOMES: With advancing pregnancy, the patient developed progressive abdominal pain, nausea, leg edema, and rising creatinine that were not responsive to ongoing therapies and required delivery via Cesarean section at 31 weeks of gestational age. LESSONS LEARNED: In the era of increasing number of pregnant renal transplant patients with multiple medical issues, we need organized approach to diagnosis of acute renal allograft injury in pregnancy and we need to consider abdominal compartment syndrome as one of the causes.

JUSTIFICATION: Le nombre croissant de grossesses chez les greffées d'un rein aux prises avec des problèmes de santé complexes oblige les cliniciens à connaître le syndrome du compartiment abdominal; un trouble qui, pendant la grossesse, peut contribuer à une insuffisance rénale aiguë du greffon. PRÉSENTATION DU CAS: Une femme nullipare de 34 ans d'origine caucasienne et atteinte d'insuffisance rénale terminale (IRT) consécutive à un diabète de type 1. La patiente avait subi une première greffe simultanée rein-pancréas en 2006 puis, pour cause de rejet, une deuxième transplantation d'un rein seulement, lequel provenait d'un donneur décédé d'un problème circulatoire. La patiente est tombée enceinte de jumeaux diachroniques et diamniotiques en mai 2013 sans procréation assistée. La grossesse a été ponctuée de deux épisodes d'insuffisance rénale aiguë du greffon. DIAGNOSTIC: IRT consécutive à un diabète de type 1, insuffisance rénale aiguë du greffon, toxicité du tacrolimus, douleurs abdominales. INTERVENTIONS PRÉVENTION ET HABITUDES DE VIE: La patiente a été réhydratée par intraveineuse, les douleurs abdominales et les nausées ont été soulagées, et les médicaments contribuant à l'insuffisance rénale ont été temporairement cessés. Le syndrome du compartiment abdominal a été traité en maintenant la pression intravasculaire et en optimisant la perfusion vasculaire locale et systémique par un équilibre hydrique approprié, en évacuant le contenu intraluminal par décompression du système gastro-intestinal, et en améliorant la compliance de la paroi abdominale par l'administration d'analgésiques, par la sédation et par le positionnement de la patiente. ISSUE: Avec la progression de la grossesse, les symptômes de douleurs abdominales, nausées, œdème aux membres inférieurs et augmentation de la créatinine ayant cessé de répondre aux traitements, la patiente a dû accoucher par césarienne à 31 semaines. ENSEIGNEMENTS TIRÉS: Le nombre croissant de femmes enceintes greffées d'un rein et atteintes de problèmes de santé complexes plaide pour une approche concertée dans le diagnostic de l'insuffisance aiguë du greffon pendant la grossesse. Le syndrome du compartiment abdominal doit être envisagé comme l'une des causes de l'insuffisance rénale aiguë en grossesse.

Outcomes Following Macrolide Use in Kidney Transplant Recipients.

BACKGROUND: Calcineurin inhibitors (CNI; cyclosporine, tacrolimus) are critical for kidney transplant immunosuppression, but have multiple potential drug interactions, such as with macrolide antibiotics. Macrolide antibiotics (clarithromycin, erythromycin, and azithromycin) are often used to treat atypical infections. Clarithromycin and erythromycin inhibit CNI metabolism and increase the risk of CNI nephrotoxicity, while azithromycin does not. OBJECTIVE: To determine the frequency of CNI-macrolide co-prescriptions, the proportion who receive post-prescription monitoring, and the risk of adverse drug events in kidney transplant recipients. DESIGN: Retrospective cohort study. SETTING: We used linked health care databases in Alberta, Canada. PATIENTS: We included 293 adult kidney transplant recipients from 2008-2015 who were co-prescribed a CNI and macrolide. MEASUREMENTS: The primary outcome was a composite of all-cause hospitalization, acute kidney injury (creatinine increase ≥0.3 mg/dL or 1.5 times baseline), or death within 30 days of the macrolide prescription. METHODS: We identified CNI-macrolide co-prescriptions and compared outcomes in those who received clarithromycin/erythromycin versus azithromycin. We used a linear mixed-effects model to examine the mean change in serum creatinine and estimated glomerular filtration rate (eGFR). RESULTS: Of the 293 recipients who were co-prescribed a CNI and a macrolide, 38% (n = 112) were prescribed clarithromycin/erythromycin while 62% (n = 181) were prescribed azithromycin. Compared with azithromycin users, clarithromycin/erythromycin users were less likely to have outpatient serum creatinine monitoring post-prescription (56% vs 69%, P = .03). There was no significant difference in the primary outcome between the 2 groups (17% vs 11%, P = .11); however, the risk of all-cause hospitalization was higher in the clarithromycin/erythromycin group (10% vs 3%, P = .02). The mean decrement in eGFR was significantly greater in the clarithromycin/erythromycin versus azithromycin group (-5.4 vs -1.9 mL/min/1.73 m2, P < .05). LIMITATIONS: We did not have CNI levels to correlate with the timing of CNI-macrolide co-prescriptions. We also did not have information regarding the indications for macrolide prescriptions. CONCLUSION: Clarithromycin and erythromycin were frequently co-prescribed in kidney transplant recipients on CNIs despite known drug interactions. Clarithromycin/erythromycin use was associated with a higher risk of hospitalization compared with azithromycin users. Safer prescribing practices in kidney transplant recipients are warranted.

CONTEXTE: Les inhibiteurs de la calcineurine (CNI : cyclosporine, tacrolimus) sont essentiels à l'immunosuppression suivant une transplantation rénale. Ils présentent toutefois de nombreux risques d'interactions médicamenteuses avec les antibiotiques macrolides (clarithromycine, érythromycine et azithromycine) employés couramment pour traiter les infections atypiques. La clarithromycine et l'érythromycine inhibent le métabolisme des CNI et augmentent leurs risques de néphrotoxicité, ce qui n'est pas le cas de l'azithromycine. OBJECTIFS: Déterminer la fréquence de co-prescription d'un CNI et d'un macrolide chez les receveurs d'une greffe rénale, la proportion de patients ayant fait l'objet d'un suivi post-prescription et le risque d'effets indésirables attribuables aux médicaments. TYPE D'ÉTUDE: Une étude de cohorte rétrospective. CADRE: Les banques de données couplées du système de santé de l'Alberta (Canada). SUJETS: Nous avons inclus 293 adultes receveurs d'un rein entre 2008 et 2015 et à qui on avait co-prescrit un CNI et un macrolide. MESURES: Le principal résultat attendu était une combinaison d'hospitalisation toutes causes, d'insuffisance rénale aigüe (hausse minimale de 0,3 mg/dL de la créatinine sérique ou équivalente à 1,5 fois la valeur mesurée initialement), ou de décès du patient dans les 30 jours suivant la prescription d'un macrolide. MÉTHODOLOGIE: Nous avons répertorié les co-prescriptions CNI-macrolide et comparé les résultats des patients traités par clarithromycine/érythromycine à ceux traités avec l'azithromycine. Nous avons employé un modèle linéaire à effets mixtes pour établir les variations moyennes dans les mesures de créatinine sérique et de DFGe. RÉSULTATS: Des 293 receveurs d'un rein ayant reçu une co-prescription CNI-macrolide, 38 % (n = 112) ont été traités avec la clarithromycine/érythromycine et 62 % (n = 181) avec l'azithromycine. Les patients ayant reçu de la clarithromycine/érythromycine étaient moins susceptibles de faire l'objet d'un suivi ambulatoire du taux de créatinine sérique post-prescription (56 % contre 69 % pour l'azithromycine, p = 0,03). Aucune différence significative n'a été observée entre les deux groupes quant au principal résultat attendu (17 % contre 11 %; p = 0,11). Cependant, les patients traités par clarithromycine/érythromycine présentaient un risque supérieur d'hospitalisation toutes causes (10 % contre 3 %; p = 0,02), et la moyenne de décroissance du DFGe pour ces patients était significativement supérieure (-5,4 mL/min/1,73 m2 contre -1,9 mL/min/1,73 m2 pour l'azithromycine; p < 0,05). LIMITES: Nous n'avions pas les niveaux de CNI corrélés avec le moment de la co-prescription CNI-macrolide, ni les indications justifiant l'ordonnance de macrolide. CONCLUSION: La clarithromycine et l'érythromycine ont été fréquemment co-prescrites aux receveurs d'une greffe rénale traités avec des CNI, malgré la connaissance des interactions médicamenteuses. Les patients recevant de la clarithromycine/érythromycine sont plus susceptibles d'être hospitalisés que ceux recevant de l'azithromycine. L'adoption de pratiques de prescription plus sûres est justifiée chez les receveurs d'une greffe rénale.

Albuminuria and posttransplant chronic kidney disease stage predict transplant outcomes.

In 2012, the KDIGO guidelines updated the classification system for chronic kidney disease to include albuminuria. Whether this classification system predicts adverse clinical outcomes among kidney transplant recipients is unclear. To evaluate this, we conducted a retrospective study using linked databases in Alberta, Canada to follow kidney transplant recipients from 2002-2011. We examined the association between an estimated glomerular filtration rate (eGFR of 60 or more, 45-59, 30-44, 15-29 mL/min/1.73 m2) and albuminuria (normal, mild, heavy) at one year post-transplant and subsequent mortality and graft loss. There were 900 recipients with a functioning graft and at least one outpatient serum creatinine and urine protein measurement at one year post-transplant. The median age was 51.2 years, 38.7% were female, and 52% had an eGFR of 60 mL/min/1.73 m2 or more. The risk of all-cause mortality and death-censored graft loss was increased in recipients with reduced eGFR or heavier albuminuria. The adjusted incidence rate per 1000 person-years of all-cause mortality for recipients with an eGFR of 15-29 mL/min/1.73 m2 and heavy albuminuria vs. an eGFR 60 mL/min/1.73 m2 or more and normal protein excretion was 117 (95% confidence interval 38-371) vs. 15 (9-23) (rate ratio 8). Corresponding rates for death-censored graft loss were 273 (88-1203) vs. 6 (3-9) (rate ratio 49). Reduced eGFR and heavier albuminuria in kidney transplant recipients are associated with an increased risk of mortality and graft loss. Thus, eGFR and albuminuria may be used together to identify, evaluate, and manage transplant recipients who are at higher risk of adverse clinical outcomes.

Anderson-Fabry cardiomyopathy: prevalence, pathophysiology, diagnosis and treatment.

Anderson-Fabry disease (AFD) is a lysosomal storage disease caused by the inappropriate accumulation of globotriaosylceramide in tissues due to a deficiency in the enzyme α-galactosidase A (α-Gal A). Anderson-Fabry cardiomyopathy is characterized by structural, valvular, vascular and conduction abnormalities, and is now the most common cause of mortality in patients with AFD. Large-scale metabolic and genetic screening studies have revealed AFD to be prevalent in populations of diverse ethnic origins, and the variant form of AFD represents an unrecognized health burden. Anderson-Fabry disease is an X-linked disorder, and genetic testing is critical for the diagnosis of AFD in women. Echocardiography with strain imaging and cardiac magnetic resonance imaging using late enhancement and T1 mapping are important imaging tools. The current therapy for AFD is enzyme replacement therapy (ERT), which can reverse or prevent AFD progression, while gene therapy and the use of molecular chaperones represent promising novel therapies for AFD. Anderson-Fabry cardiomyopathy is an important and potentially reversible cause of heart failure that involves LVH, increased susceptibility to arrhythmias and valvular regurgitation. Genetic testing and cardiac MRI are important diagnostic tools, and AFD cardiomyopathy is treatable if ERT is introduced early.

Evaluating the utility of ambulatory blood pressure monitoring in kidney transplant recipients.

Hypertension is a major risk factor for graft dysfunction and cardiovascular disease in kidney transplant recipients (KTX). Accurate monitoring is therefore essential to provide optimal therapy. We evaluated whether 24-h ambulatory blood pressure monitoring (ABPM) is superior to clinic blood pressure (CBP) measurement in prevalent KTX. Twenty-four-hour ABPM was performed in 244 prevalent KTX. The average clinic systolic blood pressure (SBP) was 137.1 ± 19.4 mm Hg, and diastolic blood pressure (DBP) was 79.9 ± 10.5 mm Hg. The ABPM average SBP was 131.3 ± 15.4 mm Hg and DBP was 75.37 ± 8.8 mm Hg; daytime ABPM average SBP was 133.5 ± 15.0 mm Hg and DBP 77.4 ± 9.1 mm Hg. The correlations between CBP, 24-h ABPM, and daytime ABPM were approximately 0.5. CBP measurements overestimate both 24-h and daytime ABPM by linear regression (p < 0.001). In this largest study to date evaluating blood pressure monitoring in KTX, we found that CBP overestimates ABPM, highlighting the prevalence of white coat hypertension. The improved accuracy of ABPM will decrease overprescribing of BP medications to avoid hypotension, drug interactions, and non-adherence. In contrast, identifying the nocturnal "non-dippers", not evident by CBP, facilitates appropriate management, as under-treatment of hypertension could lead to accelerated graft dysfunction, cardiovascular disease, and mortality. These data suggest the improved accuracy of 24-h ABPM is beneficial for BP monitoring in KTX recipients.

Accurate estimation of viral abundance by epifluorescence microscopy.

Virus enumeration by epifluorescence microscopy (EFM) is routinely done on preserved, refrigerated samples. Concerns about obtaining accurate and reproducible estimates led us to examine procedures for counting viruses by EFM. Our results indicate that aldehyde fixation results in rapid decreases in viral abundance. By 1 h postfixation, the abundance dropped by 16.4% +/- 5.2% (n = 6), and by 4 h, the abundance was 20 to 35% lower. The average loss rates for glutaraldehyde- and formaldehyde-fixed samples over the first 2 h were 0.12 and 0.13 h(-1), respectively. By 16 days, viral abundance had decreased by 72% (standard deviation, 6%; n = 6). Aldehyde fixation of samples followed by storage at 4 degrees C, for even a few hours, resulted in large underestimates of viral abundance. The viral loss rates were not constant, and in glutaraldehyde- and formaldehyde-fixed samples they decreased from 0.13 and 0.17 h(-1) during the first hour to 0.01 h(-1) between 24 and 48 h. Although decay rates changed over time, the abundance was predicted by using separate models to describe decay over the first 8 h and decay beyond 8 h. Accurate estimates of abundance were easily made with unfixed samples stained with Yo-Pro-1, SYBR Green I, or SYBR Gold, and slides could be stored at -20 degrees C for at least 2 weeks or, for Yo-Pro-1, at least 1 year. If essential, samples can be fixed and flash frozen in liquid nitrogen upon collection and stored at -86 degrees C. Determinations performed with fixed samples result in large underestimates of abundance unless slides are made immediately or samples are flash frozen. If protocols outlined in this paper are followed, EFM yields accurate estimates of viral abundance.