Ferric Derisomaltose Evaluation in Patients with Non-Dialysis-Dependent Chronic Kidney Disease or Peritoneal Dialysis.

Background: Iron deficiency anemia is common in patients with advanced chronic kidney disease (CKD). Ferric derisomaltose (FDI) enables iron repletion in a single dose, unlike other forms of iron for IV administration, which require multiple doses. Protocols are commonly used with other IV irons, but there are limited Canadian data for FDI, and no protocol exists. Objectives: To evaluate the efficacy and safety of FDI for patients with CKD and to ascertain information related to its use in Canadian provinces. Methods: This retrospective cohort study involved patients with non-dialysis-dependent CKD (NDD-CKD) and patients undergoing peritoneal dialysis (PD) who received FDI in a tertiary hospital in Nova Scotia between June 2020 and May 2021. Each patient was followed for a minimum of 6 months. The efficacy outcomes were the changes from baseline in hemoglobin, transferrin saturation (TSAT), and ferritin after the first dose of FDI and at 3 and 6 months. The safety outcomes were the frequency and types of adverse reactions to FDI. Electronic surveys were sent to 33 Canadian renal pharmacists to gather information about FDI use, dosing, administration, monitoring, funding, and safety in their respective organizations. Results: A total of 52 infusions were administered to 35 patients during the study period. The median times between doses 1 and 2 and between doses 2 and 3 were 19.1 and 6.6 weeks, respectively. The median change from baseline to first post-FDI follow-up blood work was significant for hemoglobin (9.0 g/L, p = 0.023), TSAT (11 percentage points, p < 0.001), and ferritin (271.4 µg/L, p < 0.001). Median darbepoetin doses decreased from baseline to 6 months (p < 0.001). Three adverse reactions occurred. At least 15 (65%) of the 23 survey respondents reported that FDI was funded by their province or was listed on their hospital drug formulary. Conclusion: This study provides evidence that FDI is an effective and safe treatment for anemia in NDD-CKD and PD patients.

Contexte: L'anémie ferriprive est fréquente chez les patients atteints d'insuffisance rénale chronique avancée (IRC). Une seule dose de dérisomaltose ferrique (FDI) permet au niveau de fer de se rétablir, contrairement à d'autres formes de fer administrées par IV qui nécessitent, elles, plusieurs doses. Des protocoles sont couramment utilisés avec d'autres fers administrés par IV, mais les données canadiennes sur le FDI sont limitées et il n'existe aucun protocole. Objectifs: Évaluer l'efficacité et l'innocuité du FDI chez les patients atteints d'IRC et vérifier les informations relatives à son utilisation dans les provinces du Canada. Méthodes: Cette étude de cohorte rétrospective comprenait des patients atteints d'IRC sans dialyse (NDD-IRC) et des patients sous dialyse péritonéale (DP) ayant reçu du FDI dans un hôpital de soins tertiaires de la Nouvelle-Écosse entre juin 2020 et mai 2021. Chaque patient a fait l'objet d'un suivi pendant au moins 6 mois. Les résultats d'efficacité étaient les changements par rapport à la base de trois mesures après la première dose de FDI et à 3 et 6 mois, soit l'hémoglobine, la saturation de la transferrine (TSAT) et la ferritine. Les résultats d'innocuité étaient la fréquence et les types de réactions indésirables au FDI. Des sondages ont été envoyés par voie électronique à 33 pharmaciens canadiens spécialisés en néphrologie afin de recueillir des renseignements sur l'utilisation, le dosage, l'administration, la surveillance, le financement et l'innocuité du FDI dans leurs organismes respectifs. Résultats: Au total, 52 perfusions ont été administrées à 35 patients au cours de la période d'étude. Les délais médians entre les doses 1 et 2, et entre les doses 2 et 3 étaient respectivement de 19,1 et 6,6 semaines. Le changement médian entre la base et le premier bilan sanguin de suivi post-FDI était important pour l'hémoglobine (9,0 g/L, p = 0,023), le TSAT (11 points de pourcentage, p < 0,001) et la ferritine (271,4 µg/L, p < 0,001). Les doses médianes de darbépoétine ont diminué par rapport à la base à 6 mois (p < 0,001). Trois effets indésirables se sont produits. Au moins 15 des 23 répondants au sondage (65 %) ont déclaré que le FDI était financé par leur province ou figurait sur les listes de médicaments des hôpitaux. Conclusion: Cette étude fournit des preuves que le FDI est un traitement efficace et sûr de l'anémie chez les patients NDD-IRC et PD.

Hyperkalemia: Prevalence, Predictors and Emerging Treatments.

It is well established that an elevated potassium level (hyperkalemia) is associated with a risk of adverse events including morbidity, mortality and healthcare system cost. Hyperkalemia is commonly encountered in many chronic conditions including kidney disease, diabetes and heart failure. Furthermore, hyperkalemia may result from the use of renin-angiotensin-aldosterone system inhibitors (RAASi), which are disease-modifying treatments for these conditions. Therefore, balancing the benefits of optimizing treatment with RAASi while mitigating hyperkalemia is crucial to ensure patients are optimally treated. In this review, we will briefly discuss the definition, causes, epidemiology and consequences of hyperkalemia. The majority of the review will be focused on management of hyperkalemia in the acute and chronic setting, emphasizing contemporary approaches and evolving data on the relevance of dietary restriction and the use of novel potassium binders.

Community pharmacists' perspectives on assessing kidney function and medication dosing for patients with advanced chronic kidney disease: A qualitative study using the theoretical domains framework.

Background: The kidneys are responsible for the elimination of many drugs. Chronic kidney disease (CKD) is common, and medications may require adjustment to avoid adverse outcomes. Despite the availability of kidney drug dosing resources, people with CKD are at risk of inappropriate drug prescribing. Community pharmacists are in the ideal position to mitigate harm from inappropriate prescribing in this population. Methods: In this qualitative study, community pharmacists were interviewed on their perspective on kidney function assessment and dose adjustment in people with advanced CKD (estimated glomerular filtration rate <30 mL/min/1.73 m2). The theoretical domains framework for targeting behavioural change was used to inform the interview guide and analysis. Purposeful sampling was employed until data saturation. Semistructured virtual interviews were audio-recorded, transcribed verbatim and uploaded into NVIVO 12 Pro to facilitate thematic analysis. Deductive and inductive iterative coding approaches were employed to determine categories and themes. Results: Twelve pharmacists were interviewed, with a mean age of 42 years and 16 years of experience. Four themes comprising 10 categories were identified to influence kidney function assessment and dosing, including resources (information access, technology, references), environment (pharmacy infrastructure, practice setting), reflection (triggers, experience and training, collaboration) and leadership and governance (pharmacist role, advocacy). Feedback on an optimal CKD tool was collected, and enabling themes (categories) for implementation included knowledge and skills (education, training) and reflection (role, support, integration). Conclusions: Findings will inform the interventions needed to improve implementation of kidney assessment and dosing of high-risk medications in people with kidney impairment into community pharmacy practice. Can Pharm J (Ott) 2023;156:xx-xx.

Development and Validation of Nine Deprescribing Algorithms for Patients on Hemodialysis to Decrease Polypharmacy.

BACKGROUND: Polypharmacy is ubiquitous in patients on hemodialysis (HD), and increases risk of adverse events, medication interactions, nonadherence, and mortality. Appropriately applied deprescribing can potentially minimize polypharmacy risks. Existing guidelines are unsuitable for nephrology clinicians as they lack specific instructions on how to deprescribe and which safety parameters to monitor. OBJECTIVE: To develop and validate deprescribing algorithms for nine medication classes to decrease polypharmacy in patients on HD. DESIGN: Questionnaires and materials sent electronically. PARTICIPANTS: Nephrology practitioners across Canada (nephrologists, nurse practitioners, renal pharmacists). METHODS: A literature search was performed to develop the initial algorithms via Lynn's method for development of content-valid clinical tools. Content and face validity of the algorithms was evaluated over three interview rounds using Lynn's method for determining content validity. Canadian nephrology clinicians each evaluated three algorithms (15 clinicians per round, 45 clinicians in total) by rating each algorithm component on a four-point Likert scale for relevance; face validity was rated on a five-point scale. After each round, content validity index of each component was calculated and revisions made based on feedback. If content validity was not achieved after three rounds, additional rounds were completed until content validity was achieved. RESULTS: After three rounds of validation, six algorithms achieved content validity. After an additional round, the remaining three algorithms achieved content validity. The proportion of clinicians rating each face validity statement as "Agree" or "Strongly Agree" ranged from 84% to 95% (average of all five questions, across three rounds). LIMITATIONS: Algorithm development was guided by existing deprescribing protocols intended for the general population and the expert opinions of our study team, due to a lack of background literature on HD-specific deprescribing protocols. There is no universally accepted method for the validation of clinical decision-making tools. CONCLUSIONS: Nine medication-specific deprescribing algorithms for patients on HD were developed and validated by clinician review. Our algorithms are the first medication-specific, patient-centric deprescribing guidelines developed and validated for patients on HD.

CONTEXTE: La polypharmacie est très répandue chez les patients hémodialysés et augmente le risque d'événements indésirables, d'interactions médicamenteuses, d'inobservance au traitement et de mortalité. La déprescription, appliquée de façon appropriée, peut réduire les risques associés à la polypharmacie. Les directives de déprescription existantes ne conviennent cependant pas aux cliniciens en néphrologie puisqu'elles ne renferment aucune indication spécifique sur la manière de procéder ni sur les paramètres de sécurité à surveiller. OBJECTIF: Développer et valider des algorithmes de déprescription pour neuf classes de médicaments en vue de réduire la polypharmacie chez les patients hémodialysés. CONCEPTION: Des questionnaires et des documents envoyés par voie électronique. PARTICIPANTS: Des praticiens en néphrologies de partout au Canada (néphrologues, infirmières-praticiennes, pharmaciens spécialisés en néphrologie). MÉTHODOLOGIE: Une recherche bibliographique a été effectuée pour développer les algorithmes initiaux avec la méthode de Lynn pour le développement d'outils cliniques à contenu validé. Le contenu et la validité apparente des algorithmes ont été évalués au cours de trois cycles d'interviews par la méthode de Lynn pour déterminer la validité d'un contenu. Les praticiens interviewés (15 par cycle, pour un total de 45) ont chacun évalué trois algorithmes en classant la pertinence de leurs composants sur une échelle de Likert en quatre points, et en classant leur validité apparente sur une échelle en cinq points. Après chaque cycle, l'indice de validité du contenu a été calculé pour chaque composant et des correctifs ont été apportés en fonction de la rétroaction. Si la validité du contenu n'était pas atteinte après trois cycles, des cycles supplémentaires étaient effectués jusqu'à ce que celle-ci soit atteinte. RÉSULTATS: Six algorithmes ont atteint la validité après trois cycles de validation. Les trois algorithmes restants l'ont atteint après un cycle supplémentaire. La proportion de cliniciens ayant attribué la mention de validité apparente « d'accord ¼ ou « tout à fait d'accord ¼ se situait entre 84 et 95 % (moyenne des cinq questions, sur trois cycles). LIMITES: Le développement des algorithmes repose sur les protocoles de déprescription existants, destinés à la population générale, et sur l'avis des experts de notre équipe d'étude puisque la documentation portant sur des protocoles de déprescription spécifiques aux patients hémodialysés est insuffisante. Il n'existe aucune méthode universellement acceptée pour valider les outils de décision clinique. CONCLUSION: Neuf algorithmes de déprescription spécifiques aux patients hémodialysés ont été développés et validés par révision des cliniciens. Nos algorithmes sont les premiers guides de déprescription développés et validés spécifiquement pour les médicaments des patients hémodialysés. ENREGISTREMENT DE L'ESSAI: Sans objet ­ il s'agit d'une série de questionnaires.

An Adjustable Dalteparin Sodium Dose Regimen for the Prevention of Clotting in the Extracorporeal Circuit in Hemodialysis: A Clinical Trial of Safety and Efficacy (the PARROT Study).

BACKGROUND: Dalteparin sodium, a low-molecular-weight heparin, is indicated for prevention of clotting in the extracorporeal circuit during hemodialysis (HD). Product labeling recommends a fixed single-bolus dose of 5000 international units (IU) for HD sessions lasting up to 4 hours, but adjustable dosing may be beneficial in clinical practice. OBJECTIVE: The aim of the PARROT study was to investigate the safety and efficacy of an adjustable dose of dalteparin in patients with end-stage renal disease requiring 3 to 4 HD sessions per week. DESIGN: A 7-week, open-label, multicenter study with a single treatment arm, conducted between October 2013 and March 2016. SETTING: Ten sites in Canada. PATIENTS: A total of 152 patients with end-stage renal disease requiring 3 to 4 HD sessions per week. MEASUREMENTS: The primary outcome was the proportion of HD sessions completed without premature termination due to inadequate anticoagulation. METHODS: All participants initially received a dose of 5000 IU dalteparin, which could be adjusted at subsequent HD sessions when clinically indicated, by increment or decrement of 500 or 1000 IU, with no specified dose limits. RESULTS: Patients were followed for 256 patient-months. Nearly all (99.9%; 95% confidence interval [CI]: 99.7-100) evaluable HD sessions were completed without premature clotting. Dose was adjusted for more than half (52.3%) of participants, mostly owing to clotting or access compression time >10 minutes. Median dalteparin dose was 5000 IU (range: 500-13 000 IU). There were no major bleeds, and minor bleeding was reported in 2.3% of all HD sessions. There was no evidence of bioaccumulation. LIMITATIONS: This short-term study, with a single treatment arm, was designed to optimize dalteparin dose using a flexible dosing schedule; it was not designed to specifically evaluate dalteparin dose minimization, provide a direct comparison of dalteparin versus unfractionated heparin, or provide information on long-term safety for flexible dalteparin dosing. Patients were excluded if they were at high risk of bleeding, including those on anticoagulants and those on antiplatelet agents other than aspirin <100 mg/d. CONCLUSIONS: Overall, an adjustable dalteparin sodium dose regimen allowed safe completion of HD, with clinical benefits over fixed dosing. TRIAL REGISTRATION: ClinicalTrials.gov NCT01879618, registered June 13, 2013.

CONTEXTE: La daltéparine sodique, une héparine de faible poids moléculaire, est indiquée pour prévenir la formation de caillots dans le circuit extracorporel durant l'hémodialyse (HD). Pour une séance de dialyse d'une durée maximale de quatre heures, l'étiquette du produit recommande une dose fixe de 5 000 unités internationales (U.I.) administrée en bolus. Cependant, il est possible qu'il puisse être bénéfique d'ajuster la dose en pratique. OBJECTIF: Le but de l'étude PARROT était d'analyser l'innocuité et l'efficacité d'une dose ajustable de daltéparine chez des patients atteints d'insuffisance rénale terminale (IRT) et nécessitant trois à quatre séances d'HD par semaine. TYPE D'ÉTUDE: Il s'agit d'une étude ouverte et multicentrique à traitement unique d'une durée de sept semaines couvrant la période entre octobre 2013 et mars 2016. CADRE: L'étude a eu lieu dans dix centres de dialyse au Canada. SUJETS: L'étude a inclus 152 patients atteints d'IRT et nécessitant trois à quatre séances d'HD par semaine. MESURES: Le résultat principal était la proportion de séances d'HD complétées, non interrompues de manière prématurée en raison d'une anticoagulation inadéquate. MÉTHODOLOGIE: Tous les participants ont initialement reçu 5000 U.I. de daltéparine, dose qui a pu être ajustée lors des séances subséquentes, lorsqu'indiqué par le contexte clinique, à raison d'augmentation ou de réduction de 500 ou 1 000 U.I., sans spécification quant aux doses limites. RÉSULTATS: Les patients ont été suivis sur une période de 256 mois-patients. Pratiquement toutes les séances d'HD évaluables (99,9 %; IC 95 % : 99,7-100) ont été complétées sans coagulation prématurée. La dose de daltéparine a été ajustée pour plus de la moitié (52,3 %) des participants, essentiellement en raison de coagulation ou d'un besoin de procéder à une compression de l'accès vasculaire au-delà de 10 minutes. La dose médiane de daltéparine était de 5 000 U.I. (entre 500 et 13 000 U.I.). Aucune hémorragie majeure n'a été rapportée, mais une hémorragie mineure est survenue dans 2,3 % de toutes les séances d'HD analysées. Aucune bioaccumulation n'a été détectée. LIMITES: Cette étude de courte durée à traitement unique a été conçue pour optimiser le dosage de daltéparine à l'aide d'un schéma de posologie flexible. Elle ne visait pas à évaluer spécifiquement la minimisation de la dose ou à fournir des informations sur l'innocuité à long terme d'une posologie flexible pour la daltéparine. Également, les patients à haut risque d'hémorragie ont été exclus de l'étude, notamment ceux qui prenaient des anticoagulants ou des antiplaquettaires autres qu'une dose quotidienne de moins de 100 mg d'aspirine. CONCLUSION: Dans l'ensemble, un schéma posologique flexible pour la daltéparine sodique a permis de compléter les séances d'HD de façon sécuritaire, en plus de fournir des avantages cliniques par rapport à une dose fixe.

Effectiveness and Cost of Weekly Recombinant Tissue Plasminogen Activator Hemodialysis Catheter Locking Solution.

BACKGROUND AND OBJECTIVES: Evidence to guide hemodialysis catheter locking solutions is limited. We aimed to assess effectiveness and cost of recombinant tissue plasminogen activator (rt-PA) once per week as a locking solution, compared with thrice weekly citrate or heparin, in patients at high risk of complications. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used a prospective design and pre-post comparison in three sites across Canada. Pre-post comparisons were conducted using multilevel mixed effects regression models accounting for cluster with site and potential enrollment of patients more than once. In the pre period, catheter malfunction was managed as per site-specific standard of care. The intervention in the post period was once weekly rt-PA as a locking solution (with citrate or heparin used for other sessions). The primary outcome was rate of rt-PA use for treatment of catheter malfunction. Secondary outcomes included rates of bacteremia, management of catheter malfunction, and cost. RESULTS: There were 374 patients (mean age 68 years; 52% men) corresponding to 506 enrollments. Mean length of enrollment was 200 days (SD 119) in the pre period and 187 days (SD 101) in the post period. There was a significant decline in rate of rt-PA use for treatment of catheter malfunction in the post compared with pre period (adjusted incidence rate ratio, 0.39; 95% confidence interval, 0.30 to 0.52); however, there was no difference in the rate of bacteremia, or catheter stripping or removal/replacement. The increase in mean total health care cost in the post period was CAD$962 per enrollment, largely related to costs of rt-PA as a locking solution. CONCLUSIONS: Once weekly rt-PA as a catheter locking solution was associated with a reduction in rt-PA use for treatment of catheter malfunction. Our results showing a reduction in rescue rt-PA use are consistent with a prior randomized trial, although we did not observe a reduction in bacteremia or catheter stripping/removal and did observe an increased incremental cost of this strategy primarily accounted for by the cost of the rt-PA.

An Evaluation of Medication Reconciliation in an Outpatient Nephrology Clinic.

Background: Accreditation Canada recognizes medication reconciliation as a key required organizational practice (ROP) to enhance patient safety. Patients with chronic kidney disease (CKD) carry a high risk for adverse drug events due to multiple co-morbidities, using many medications, and being cared for by many practitioners. Data evaluating the benefits of ambulatory medication reconciliation (AmbMR) in patients with advanced CKD is limited. Methods: We retrospectively evaluated types and rates of medication discrepancies and their potential index for patient harm using the Cornish classification system in a cohort of consecutive non-dialysis-dependent CKD stage 5 patients who received AmbMR. Results: AmbMR was conducted 225 times on 115 patients during the study period. One hundred eighty medication discrepancies were identified. The most common discrepancy identified was incorrect drug followed by discrepant dose, discrepant frequency, and drug omission. Sixty-three percent of discrepancies were classified as unlikely to cause patient discomfort or clinical deterioration, 36% were classified as likely to cause moderate harm, and one percent was classified as potential to cause serious harm. Conclusion: Medication discrepancies are common in patients with advanced CKD. Nearly a quarter of patients may experience moderate discomfort or clinical deterioration from discrepancies. Our study showed that in patients with non-dialysis-dependent CKD stage 5, the risk of patient harm associated with medication discrepancies can be reduced by conducting AmbMR.

Ambulatory Medication Reconciliation in Dialysis Patients: Benefits and Community Practitioners' Perspectives.

BACKGROUND: Ambulatory medication reconciliation can reduce the frequency of medication discrepancies and may also reduce adverse drug events. Patients receiving dialysis are at high risk for medication discrepancies because they typically have multiple comorbid conditions, are taking many medications, and are receiving care from many practitioners. Little is known about the potential benefits of ambulatory medication reconciliation for these patients. OBJECTIVES: To determine the number, type, and potential level of harm associated with medication discrepancies identified through ambulatory medication reconciliation and to ascertain the views of community pharmacists and family physicians about this service. METHODS: This retrospective cohort study involved patients initiating hemodialysis who received ambulatory medication reconciliation in a hospital renal program over the period July 2014 to July 2016. Discrepancies identified on the medication reconciliation forms for study patients were extracted and categorized by discrepancy type and potential level of harm. The level of harm was determined independently by a pharmacist and a nurse practitioner using a defined scoring system. In the event of disagreement, a nephrologist determined the final score. Surveys were sent to 52 community pharmacists and 44 family physicians involved in the care of study patients to collect their opinions and perspectives on ambulatory medication reconciliation. RESULTS: Ambulatory medication reconciliation was conducted 296 times for a total of 147 hemodialysis patients. The mean number of discrepancies identified per patient was 1.31 (standard deviation 2.00). Overall, 30% of these discrepancies were deemed to have the potential to cause moderate to severe patient discomfort or clinical deterioration. Survey results indicated that community practitioners found ambulatory medication reconciliation valuable for providing quality care to dialysis patients. CONCLUSIONS: This study has provided evidence that ambulatory medication reconciliation can increase patient safety and potentially prevent adverse events associated with medication discrepancies.

CONTEXTE: Le bilan comparatif des médicaments en soins ambulatoires peut réduire les divergences au chapitre des médicaments et les événements indésirables liés aux médicaments. Les divergences relatives aux médicaments représentent un risque élevé pour les patients dialysés, car ils souffrent normalement de multiples troubles comorbides, ils prennent souvent de nombreux médicaments et ils sont soignés par bon nombre de praticiens. Peu d'information existe sur les possibles avantages du bilan comparatif des médicaments en soins ambulatoires pour ces patients. OBJECTIFS: Déterminer le nombre et la catégorie des divergences concernant les médicaments constatées lors d'un bilan comparatif des médicaments en soins ambulatoires ainsi que la gravité potentielle des préjudices consécutifs. De plus, établir la position des pharmaciens communautaires et des médecins de famille sur cette modalité du bilan comparatif des médicaments. MÉTHODES: La présente étude de cohorte rétrospective a été menée auprès de patients amorçant un traitement par hémodialyse pour qui un bilan comparatif des médicaments en soins ambulatoires a été réalisé dans le cadre d'un programme hospitalier des maladies du rein, entre juillet 2014 et juillet 2016. Les divergences trouvées dans les formulaires de bilan comparatif des médicaments ont été classées par catégorie et selon la gravité potentielle des préjudices. Le niveau du préjudice a été déterminé de manière indépendante par un pharmacien et un membre du personnel infirmier praticien à l'aide d'un système de notation défini. En cas de désaccord, le score final était établi par un néphrologue. Des sondages ont été envoyés à 52 pharmaciens communautaires et à 44 médecins de famille prodiguant des soins aux participants afin qu'ils expriment leurs opinions et leurs points de vue sur le bilan comparatif des médicaments en soins ambulatoires. RÉSULTATS: En tout, 296 bilans comparatifs des médicaments en soins ambulatoires ont été effectués auprès de 147 patients hémodialysés. Le nombre moyen de divergences constatées par patient était de 1,31 (écart-type de 2,00). Dans l'ensemble, 30 % de ces divergences ont été considérées comme une source potentielle d'un inconfort allant de modéré à grave ou de dégradation clinique. Selon les résultats du sondage, les praticiens communautaires ont jugé le bilan comparatif des médicaments en soins ambulatoires utile à la prestation de soins de qualité aux patients dialysés. CONCLUSIONS: D'après les résultats de l'étude, le bilan comparatif des médicaments en soins ambulatoires augmenterait la sécurité des patients et pourrait prévenir les événements indésirables liés aux divergences relatives aux médicaments.

Comparison of intensive versus standard hemodialysis central venous catheter dysfunction protocol using rt-PA: a quality assurance initiative.

PURPOSE: Catheter locking solutions such as recombinant tissue plasminogen activator (rt-PA) are used to treat and prevent clotting of hemodialysis (HD) catheters during HD treatments and the interdialytic period. However, evidence to guide the use of rt-PA for catheter dysfunction is limited. METHODS: We evaluated outcomes using two catheter dysfunction protocols in a cohort of consecutive prevalent dialysis patients (Jan 2013 to Sep 2014) undergoing HD with a tunneled catheter. In the intensive protocol, rt-PA was administered to all catheters based on blood flow and/or line reversal. In the standard protocol, rt-PA administration was based only on blood flow. The primary outcome was the rate of rt-PA use for catheter malfunction (rt-PA treatment days/1000 total line days; [TLD]). Secondary outcomes included the cost of rt-PA/TLD and the rate of catheter-related bacteremia. RESULTS: There were 26 and 35 patients managed by the intensive and standard protocols, respectively. The rate of rt-PA use was 52/1000 TLD (intensive) versus 39/1000 TLD (standard) (rate ratio 1.30, 95% CI 1.12-1.52 CI, p<0.001). The rate of bacteremia was 0.43 and 0.22/1000 TLD for the intensive and standard protocols, respectively (p = 0.491). The cost of rt-PA was CDN $5.58 and CDN $6.15 per TLD for the intensive protocol and standard protocol groups (p<0.001). CONCLUSIONS: Managing catheter dysfunction based on line reversal and blood flow as opposed to only blood flow was associated with a higher rate of rt-PA use, but at a reduced overall cost.

An evaluation of oral dabigatran etexilate pharmacokinetics and pharmacodynamics in hemodialysis.

Dabigatran etexilate represents a possible improved alternative to warfarin for anticoagulation in hemodialysis patients with atrial fibrillation (AF). The objective was to determine dabigatran plasma concentrations and anticoagulant effects following administration of a single 110 mg oral dose of dabigatran etexilate to 10 adult patients immediately prior to starting hemodialysis. Mass spectrometry and the Hemoclot® assay were used, respectively, to determine free (unconjugated) dabigatran concentrations and thrombin time (TT) in plasma samples collected intermittently over 48 hours. The median time (tmax ) to reach the maximum plasma-free dabigatran concentration (Cmax ) was 2 hours (range 1-3 hours). The mean free dabigatran Cmax was 95.5 ± 33.4 ng/mL. The mean elimination half-lives on and off hemodialysis were, respectively, 2.6 ± 1.3 and 30.2 ± 7.8 hours. Hemodialysis effectively removed dabigatran with an extraction ratio of 0.63 ± 0.07. The maximal TT ratio was 2.1 and the TT ratio demonstrated a strong linear dependence on free dabigatran concentration (r(2) = 0.741). A 110 mg oral dabigatran dose prior to hemodialysis was rapidly absorbed and achieved therapeutic concentrations. Hemodialysis effectively removed dabigatran from the plasma and may be an effective means of accelerating the elimination of dabigatran in circumstances of excessive anticoagulation.

Recent Changes in Anemia Management: The Kidney Disease Improving Global Outcomes (KDIGO) Anemia Guideline versus the Canadian Society of Nephrology (CSN).

The management of anemia is important for health outcomes for people with chronic kidney disease (CKD). Global evidenced-based guidelines must be placed in the Canadian context to be relevant to guide practice. This paper summarizes the response of the Canadian Society of Nephrology to global anemia management guidelines in CKD and the implications for practice.

Canadian Society of Nephrology commentary on the 2012 KDIGO Clinical Practice Guideline for Anemia in CKD.

The KDIGO (Kidney Disease: Improving Global Outcomes) 2012 clinical practice guideline for anemia management in patients with chronic kidney disease provides the structural and evidence base for the Canadian Society of Nephrology commentary on this guideline's relevancy and application to the Canadian health care system. While in general agreement, we provide commentary on 11 of the 61 KDIGO guideline statements. Specifically, we agreed that a therapeutic trial of iron is appropriate in cases in which a reduction in erythropoiesis-stimulating agent (ESA) dosage or avoidance of ESA and transfusion is desired, transferrin saturations are >30%, and ferritin concentrations are >500 µg/L. However, we concluded that there is insufficient evidence to support an upper target or threshold for ferritin and transferrin saturation levels. We agree with the initiation of ESA treatment when hemoglobin (Hb) level is 90-100 g/L; however, we specifically state that an acceptable range for Hb level is 95-115 g/L, with a target of 100-110 g/L, and add caution to individualization above this range due to concerns regarding the safety of ESAs. We agree that ESAs should be used with considerable caution in patients with active malignancy, history of stroke, or history of malignancy, and we suggest initiating ESA therapy at Hb level of 90 g/L and to aim for a Hb level in the range of 90-105 g/L. The reader is encouraged to note the level of evidence and review the entire KDIGO anemia guideline to interpret the guideline statements and commentary appropriately.

Oral sodium thiosulfate as maintenance therapy for calcific uremic arteriolopathy: a case series.

BACKGROUND: Calcific uremic arteriolopathy (CUA) is a rare but serious disorder affecting 4% of dialysis patients. Intravenous sodium thiosulfate (IV STS) has been shown as an effective treatment. In Canada, the average cost of IV STS is about CAD 12,000 per month, while the cost of compounded oral STS is CAD 45 per month. METHODS: Prospective cohort where all patients diagnosed with CUA during the year 2011 were included. They were treated initially with IV STS. Afterwards, each patient had a baseline bone scan and was started on oral STS for a total of 6 months followed by a repeat bone scan. A single radiologist, blinded to the dates of both scans for a given patient, read all scans. RESULTS: Four patients were studied. The intravenous dose used was 25 g three times a week for an average duration of 131 days. After the maintenance therapy, 2 patients developed further regression of the lesions, 1 had stable lesions, and 1 got worse; however, nonadherence to the drug was confirmed. The oral medication was well tolerated with no reported side effects. CONCLUSION: Oral STS, after IV STS, seems to stabilize, or even improve CUA lesions, and therefore could be useful as maintenance therapy, especially since its cost is much more reasonable than IV STS and due to the ongoing shortage of the IV formulation.