Efficacy of ferumoxytol versus sodium ferric gluconate in anemia management in outpatient hemodialysis patients: A prospective cohort study.

BACKGROUND: Intravenous iron is one of the main therapies for anemia management in hemodialysis-dependent patients. Data comparing the efficacy of ferumoxytol versus other parenteral iron supplements are scarce. The objective of the study was to compare the efficacy of ferumoxytol with that of sodium ferric gluconate in outpatient hemodialysis patients. MATERIALS AND METHODS: A prospective, observational study was conducted in outpatients receiving ferumoxytol 510 mg once or twice quarterly compared to sodium ferric gluconate 125 mg weekly in a single center hemodialysis center in Ontario, Canada. Patient demographics, hemoglobin levels, iron indices, iron doses, and erythropoiesis-stimulating agent (ESA) doses were collected. RESULTS: The study sample consisted of 291 observations from 173 patients. Generalized estimating equations of multiple linear regression modeling were conducted to compare the outcomes while adjusting for baseline scores. Approximately 25% of the study participants received ferumoxytol while 75% received sodium ferric gluconate. Patients treated were mainly males (58.4%), and the mean age was 68.73 (SD ± 13.03) years. Both groups did not show significant differences in their hemoglobin levels (Wald z = 0.54; p = 0.46), ESA utilization at 3 months (Wald z = 0.20; p = 0.65), and TSAT levels (Wald z = 3.45; p = 0.06). However, the iron levels (Wald z = 4.24; p = 0.04) and ferritin levels (Wald z = 5.14; p = 0.02) were higher in the ferric gluconate group (Wald z = 58.78; p ≤ 0.001), and patients who received ferumoxytol received more blood transfusions as compared to those who received sodium ferric gluconate (χ2 = 16.71; p ≤ 0.001). CONCLUSION: Both iron products maintained hemoglobin levels, but patients receiving ferumoxytol had lower iron indices and received more blood transfusions compared to patients who received sodium ferric gluconate.

Role of nephrology pharmacists in the management of anemia in outpatient dialysis units: A Canadian model
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INTRODUCTION: Hemodialysis patients frequently suffer from anemia. Proper utilization of therapies such as iron and erythropoiesis-stimulating agents (ESAs) is crucial to attain symptom management and established hemoglobin targets. The purpose of this study was to evaluate the clinical and financial impact of nephrology-trained pharmacists on anemia management in these patients. MATERIALS AND METHODS: A retrospective study of outpatient hemodialysis patients observed between January 2010 and December 2011. In December 2010, pharmacists were tasked to manage anemia under a medical directive. Primary endpoints were compared across years using a mixed-effects model strategy. An unstructured random effects correlation matrix was utilized to capture patient-level variation in 2010 and 2011, separately. RESULTS: Of 202 patients identified, 163 contributed in both years, 57% were males, aged 65.18 ± 16.3 years. Hemoglobin levels were 10.95 ± 0.95 and 10.83 ± 0.94 g/dL in 2010 vs. 2011, respectively (p = 0.158), while the transfusion rate was 1.3% and 1.8%, respectively (p = 0.196). Ferritin levels of 273.5 ± 22 and 317.1 ± 12 ng/mL (p = 0.0019), iron saturation 0.30 ± 0.11 and 0.30 ± 0.05 (p = 0.838), and parenteral iron dose of 215.4 ± 100.2 and 317.1 ± 123.7 mg, respectively (p = 0.996), were identified. Finally, the average weekly ESA dose in 2010 was higher and trending up as compared to 2011 where it significantly trended down. The amount of intravenous erythropoietin alfa was 12,315.6 ± 76 vs. 11,364.1 ± 52 units/week, respectively (p = 0.0556) with expenditure of 2.8 million Canadian dollars in 2010 vs. 2.3 million Canadian dollars in 2011. CONCLUSION: The participation of a nephrology pharmacist resulted in favorable outcomes in dose optimization, decreased expenditure, and positive trends in therapeutic goal achievement.

Efficacy of alteplase 1 versus 2 mg dose in restoring haemodialysis catheter function (Alte-dose 2): A randomized double-blind controlled study.

AIM: Data about the optimal alteplase dose required to treat haemodialysis catheter occlusion (HDC) are scarce. The purpose of the clinical trial was to examine the effectiveness of alteplase 2 mg as compared with 1 mg in restoring HDC function. METHODS: A double-blind, randomized, controlled clinical trial was conducted in a single-centre in southwestern Ontario, Canada. Rate of clot resolution, catheter replacements, catheter stripping, and mean catheter survival time were assessed using Kaplan-Meier, Cox-proportional hazard and clustered logic regression analyses. RESULTS: On a sample of 48 haemodialysis patients who provided 252 catheter occlusion events, the rate of clot resolution at the catheter site in the 2 mg group was 85.7% as opposed to 84.9% in the 1 mg group. There were only six catheter removals and 10 catheter stripping events. Cox regression analysis revealed no difference between the two groups in the hazard of occlusion on the primary 48 observations after the initial alteplase management (P = 0.267; hazard ratio = 0.72; 95% confidence interval 0.40-1.3). Correlated logistic regression on all 252 observations indicated no difference in the rate of post alteplase clot resolution (P = 0.336; odds ratio = 2.4, 95% confidence interval 0.399-14.6) between the two groups. CONCLUSION: Alteplase 1 mg is as effective as 2 mg in restoring HDC malfunction and may result in cost reduction in haemodialysis units.

TTP/HUS: observational studies generate hypotheses that lead to randomized controlled trials.

Thrombotic thrombocytopenic purpura (TTP)/hemolytic uremic syndrome (HUS) is a disease syndrome, and its history exemplifies how small observational studies lead to hypotheses that spawn randomized control trials (RCTs). Moschowitz's original case report coupled with the case findings of Bukowski and Byrne led to the RCT of Rock and the Canadian Apheresis Group that proved plasma exchange was superior to plasma infusion for the treatment of adults with TTP/HUS. Our single case report of continuous plasma exchange coupled with the observations about the pathogenic role of von Willebrand multimer protease of Tsai and Furlan strengthened by a 25-year observational study of plasma exchange treatment for TTP/HUS has led to a proposal to initiate a new RCT.

Salvage of Hemodialysis Catheter in Staphylococcal Bacteremia: Case Series, Revisiting the Literature, and the Role of the Pharmacist.

Catheter-related blood stream infections comprise a major concern in hemodialysis patients, leading to increased mortality, morbidity, and cost of treatment. Prompt appropriate systemic antibiotics treatment, which includes administration of appropriate systemic antibiotics and, frequently, catheter removal and replacement, is warranted. However, in hemodialysis patients, repeated catheter insertions may cause central vein stenosis and thrombosis which limits the future availability of hemodialysis access. Lock solutions containing antibiotics and anticoagulants, instilled directly into the catheter lumen after each dialysis, have been successfully utilized for catheter salvage but higher rates of recurrence and complications were observed in infections resulting from staphylococcal species. We report several cases of catheter salvage using antibiotic lock solution in staphylococcal bacteremia with the purpose of stimulating the interest in randomized clinical trials. Evaluating the risk and benefits of catheter salvage in this patient subset in light of optimized systemic antibiotic dosing, improved lock solution use, and multidisciplinary involvement, balanced with the critical need to prevent unnecessary vascular trauma, is of great importance.

Outcomes Associated with Conventional Accelerated Versus Once-Weekly IV Iron Therapy in Outpatients Undergoing Hemodialysis.

BACKGROUND: Although parenteral iron replacement is a key aspect of managing anemia in patients who are undergoing hemodialysis, studies evaluating novel iron dosing regimens are scarce. OBJECTIVE: To compare the effectiveness of a once-weekly IV iron dosing strategy with that of a conventional accelerated iron dosing regimen in patients undergoing hemodialysis. METHODS: In this retrospective cohort study, patient-specific information was collected for individuals undergoing hemodialysis who received IV iron between June 1, 2010, and June 30, 2012, at a community hospital in southwestern Ontario. The primary outcomes were hemoglobin level and utilization of an erythropoiesis-stimulating agent for 2 groups of patients: those receiving iron according to a once-weekly IV regimen and those receiving iron by a conventional accelerated IV regimen. RESULTS: Of the 148 patients who met the inclusion criteria, 99 (66.9%) received iron by a conventional accelerated regimen and 49 (33.1%) by a once-weekly IV regimen. Generalized estimating equations developed from 313 observations obtained from these 148 patients suggested that average transferrin saturation percentage and iron concentration were both significantly higher in the group that received iron once weekly than in the group that received iron by the conventional accelerated regimen (p = 0.014 and 0.008, respectively). The mean weekly dose of erythropoiesis-stimulating agent was significantly lower in the once-weekly administration group than in the conventional administration group (7419 versus 10 706 units; p = 0.041). The 2 groups did not differ significantly in terms of hemoglobin concentration (p = 0.46) or ferritin level (p = 0.13). CONCLUSIONS: The findings of this study suggest that a once-weekly iron dosing regimen may be superior to a conventional accelerated dosing regimen for managing iron deficiency anemia in patients who are undergoing hemodialysis.

CONTEXTE: Bien que la recharge en fer par voie parentérale représente un facteur clé de la prise en charge de l'anémie de patients traités par hémodialyse, il n'y a que très peu d'études évaluant les nouveaux schémas posologiques de fer. OBJECTIF: Comparer l'efficacité réelle d'une dose hebdomadaire de fer administrée par voie intraveineuse à celle d'un schéma posologique intensif traditionnel de fer chez les patients hémodialysés. MÉTHODES: Dans la présente étude de cohorte rétrospective, on a recueilli des données sur des patients traités par hémodialyse qui ont reçu du fer par voie intraveineuse entre le 1er juin 2010 et le 30 juin 2012 dans un hôpital communautaire du sud-ouest de l'Ontario. Les principaux paramètres d'évaluation étaient le taux d'hémoglobine et l'emploi d'un agent stimulant l'érythropoïèse chez deux groupes de patients : l'un recevant du fer à raison d'une dose hebdomadaire par voie intraveineuse et l'autre selon un schéma posologique intensif traditionnel par voie intraveineuse. RÉSULTATS: Parmi les 148 patients ayant satisfait aux critères d'admissibilité, 99 (66,9 %) ont reçu du fer selon un schéma posologique intensif traditionnel et 49 (33,1 %) l'ont reçu à raison d'une dose hebdomadaire par voie intraveineuse. Des équations d'estimation généralisée élaborées à partir de 313 observations obtenues de ces 148 patients laissent croire que les pourcentages moyens de saturation de la transferrine et de la concentration de fer étaient tous deux nettement plus élevés dans le groupe ayant reçu du fer une fois par semaine que dans le groupe en ayant reçu selon le schéma posologique intensif traditionnel (respectivement p = 0,014 et 0,008). La dose hebdomadaire moyenne d'un agent stimulant l'érythropoïèse était significativement plus faible au sein du groupe recevant une dose de fer hebdomadaire que dans le groupe de traitement traditionnel (7 419 contre 10 706 unités; p = 0,041). Les taux d'hémoglobine (p = 0,46) ou de ferritine (p = 0,13) ne variaient pas de façon significative entre les deux groupes. CONCLUSIONS: Selon les résultats de la présente étude, une dose hebdomadaire de fer serait plus efficace que le schéma posologique intensif traditionnel pour traiter l'anémie par carence en fer chez les patients hémodialysés.

Cloxacillin-induced seizure in a hemodialysis patient.

We are reporting a cloxacillin-induced seizure in a patient with stage 5 chronic kidney disease requiring hemodialysis. To our knowledge, there are no published case reports of seizures induced by parenteral cloxacillin in hemodialysis patients. A young hemodialysis female was admitted to the hospital with decreased level of consciousness. Blood cultures revealed methicillin-sensitive Staphylococcus aureus where cloxacillin 2 g intravenously every 4 hours was initiated. Head computed tomography (CT) was not significant. After 14 hours of cloxacillin therapy (4 doses), the patient demonstrated tonic/clonic seizure activity, where phenytoin and lorazepam were initiated. The anti-seizure medications partially reduced seizure activity. Once the cloxacillin was discontinued, the seizures stopped. Two weeks later, all anti-seizure medications were stopped with no further seizure activity. Cloxacillin elimination in hemodialysis patients is similar to patients with normal kidney function. Although cloxacillin does not significantly cross the blood-brain barrier, the correlation between the start of seizures and cloxacillin initiation was confirmed by the negative CT and blood chemistry laboratory results. Moreover, seizure activity was terminated upon discontinuation of cloxacillin. Although further investigation for the cause of such seizures is warranted, clinicians should use caution when giving high doses of cloxacillin in hemodialysis patients.

Comparison of alteplase (tissue plasminogen activator) high-dose vs. low-dose protocol in restoring hemodialysis catheter function: the ALTE-DOSE study.

Hemodialysis catheter (HDC) dysfunction due to thrombosis is common, and dysfunction incidence can reach up to 50% within 1 year of use. Although administration of intraluminal alteplase (tissue plasminogen activator [tPA]) is the standard of practice to pharmacologically restore HDC function, there are no evidence-based guidelines concerning the optimal tPA dose. The purpose of this study was to compare the efficacy of 1.0-mg vs. 2.0-mg tPA dwell protocols in restoring the HDC function in thrombotic dysfunctional catheters. A retrospective, single-center study was conducted on two independent cohorts of patients; the first (n = 129) received 2.0 mg tPA/catheter lumen, while the second (n=108) received 1.0 mg tPA/catheter lumen. Kaplan-Meier and Cox regression analyses were performed to compare the catheter survival time between patients who received 1.0 mg tPA and those who received 2.0 mg tPA. Catheter removal occurred in 25 (19.4%) of those catheters treated with 1.0 mg tPA compared with 11 (10.2%) of catheters treated with 2.0 mg tPA (P = 0.05). The hazard ratio (HR) for catheter removal was 2.75 (95% confidence interval [(95%) CI] = 1.25-6.04) for the 1.0-mg tPA cohort compared with the 2.0-mg tPA cohort. Correction added on 3 December 2012, after first online publication: The tPA cohort values were changed. Female gender (HR = 2.51; (95%) CI = 1.20-5.27) and age (HR = 0.96; (95%) CI = 0.94-0.98) were also associated with catheter survival. Our findings suggest that treatment of dysfunctional HDC with 2.0-mg tPA dwells is superior to 1.0-mg tPA dwells.