The Safety and Efficacy of Mineralocorticoid Receptor Antagonists in Patients Who Require Dialysis: A Systematic Review and Meta-analysis.

BACKGROUND: Patients who require dialysis are at high risk for cardiovascular mortality, which may be improved by mineralocorticoid receptor antagonists (MRAs). STUDY DESIGN: Systematic review and meta-analysis of randomized controlled trials. SETTING & POPULATION: Adults undergoing long-term hemodialysis or peritoneal dialysis with or without heart failure. SELECTION CRITERIA FOR STUDIES: Randomized controlled trials evaluating an MRA in dialysis and reported at least one outcome of interest. INTERVENTION: Spironolactone (8 trials) or eplerenone (1 trial) compared to placebo (7 trials) or standard of care (2 trials). OUTCOMES: Cardiovascular and all-cause mortality, hyperkalemia, serum potassium level, hypotension, change in blood pressure, and gynecomastia. RESULTS: We identified 9 trials including 829 patients. The overall quality of evidence was low due to methodologic limitations in most of the included trials. The relative risk (RR) for cardiovascular mortality was 0.34 (95% CI, 0.15-0.75) for MRA-treated compared with control patients. The RR for all-cause mortality was 0.40 (95% CI, 0.23-0.69). The RR for hyperkalemia for MRA treatment was 3.05 (95% CI, 1.21-7.70). Sensitivity analyses demonstrated wide variability in RRs for cardiovascular mortality, all-cause mortality, and hyperkalemia, suggesting further uncertainty in the confidence of the primary results. LIMITATIONS: Trial quality and size insufficient to robustly and precisely identify a treatment effect. CONCLUSIONS: Given the uncertainty of both the benefits and harms of MRAs in dialysis, large high-quality trials are required.

The Association Between Intradialytic Symptom Clusters and Recovery Time in Patients Undergoing Maintenance Hemodialysis: An Exploratory Analysis.

Background: Individuals receiving hemodialysis often experience concurrent symptoms during treatment and frequently report feeling unwell after dialysis. The degree to which intradialytic symptoms are related, and which specific symptoms may impair health-related quality of life (HRQoL) is uncertain. Objectives: To explore intradialytic symptoms clusters, and the relationship between intradialytic symptom clusters with dialysis treatment recovery time and HRQoL. Design/setting: We conducted a post hoc analysis of a prospective cohort study of 118 prevalent patients receiving hemodialysis in two centers in Calgary, Alberta and Hamilton, Ontario, Canada. Participants: Adults receiving hemodialysis treatment for at least 3 months, not scheduled for a modality change within 6 weeks of study commencement, who could provide informed consent and were able to complete English questionnaires independently or with assistance. Methods: Participants self-reported the presence (1 = none to 5 = very much) of 10 symptoms during each dialysis treatment, the time it took to recover from each treatment, and weekly Kidney Disease Quality of Life 36-Item-Short Form (KDQoL-36) assessments. Principal component analysis identified clusters of intradialytic symptoms. Mixed-effects, ordinal and linear regression examined the association between symptom clusters and recovery time (categorized as 0, >0 to 2, >2 to 6, or >6 hours), and the physical component and mental component scores (PCS and MCS) of the KDQoL-36. Results: One hundred sixteen participants completed 901 intradialytic symptom questionnaires. The most common symptom was lack of energy (56% of treatments). Two intradialytic symptom clusters explained 39% of the total variance of available symptom data. The first cluster included bone or joint pain, muscle cramps, muscle soreness, feeling nervous, and lack of energy. The second cluster included nausea/vomiting, diarrhea and chest pain, and headache. The first cluster (median score: -0.56, 25th to 75th percentile: -1.18 to 0.55) was independently associated with longer recovery time (odds ratio [OR] 1.62 per unit difference in score, 95% confidence interval [CI]: 1.23-2.12) and decreased PCS (-0.72 per unit difference in score, 95% CI: -1.29 to -0.15) and MCS scores (-0.82 per unit difference in score, 95% CI: -1.48 to -0.16), whereas the second cluster was not (OR 1.24, 95% CI: 0.97-1.58; PCS 0.19, 95% CI -0.46 to 0.83; MCS -0.72, 95% CI: -1.50 to 0.06). Limitations: This was an exploratory analysis of a small data set from 2 centers. Further work is needed to externally validate these findings to confirm intradialytic symptom clusters and the generalizability of our findings. Conclusions: Intradialytic symptoms are correlated. The presence of select intradialytic symptoms may prolong the time it takes for a patient to recover from a dialysis treatment and impair HRQoL.

Contexte: Il arrive fréquemment que les personnes qui reçoivent des traitements d'hémodialyse éprouvent des symptômes concomitants pendant la dialyze et signalent un malaise après le traitement. On en sait toutefois peu sur le degré de corrélation de ce malaise avec les symptômes intradialytiques et sur les symptômes précis qui peuvent altérer la qualité de vie liée à la santé (QVLS). Objectifs: Explorer différents groupes de symptômes intradialytiques et la relation de ceux-ci avec le temps de récupération post-dialyze et la QVLS. Cadre et conception de l'étude: Nous avons procédé à une analyze post-hoc d'une étude de cohorte prospective portant sur 118 patients prévalents recevant une hémodialyse dans deux centers, soit à Calgary (Alberta) et à Hamilton (Ontario) au Canada. Sujets: Des adultes qui recevaient des traitements d'hémodialyse depuis au moins trois mois ­ sans changement de modalité prévu dans les six semaines suivant le début de l'étude ­ qui pouvaient donner leur consentement éclairé et qui étaient en mesure de remplir des questionnaires en anglais de façon autonome ou avec de l'aide. Méthodologie: Pour chaque traitement de dialyze, les participants devaient autoévaluer le degré de présence (de 1 [non présent] à 5 [très présent]) de dix symptômes et le temps nécessaire pour récupérer de chaque traitement, puis remplir des évaluations hebdomadaires à l'aide du questionnaire KDQoL-36. Une analyze des composantes principales a permis de définir des groupes de symptômes intradialytiques. Une régression à effets mixtes, ordinale et linéaire, a servi à examiner l'association entre les groupes de symptômes et le temps de récupération (0 heure; de 0 à 2 heures; de 2 à 6 hures; plus de 6 heures), et les scores des composantes physiques et psychologiques du KDQoL-36. Résultats: Cent seize patients ont rempli un total de 901 questionnaires sur les symptômes intradialytiques. Le symptôme le plus fréquemment déclaré était le manque d'énergie (56 % des traitements). Deux groupes de symptômes intradialytiques ont expliqué 39 % de la variance totale des données disponibles sur les symptômes. Le premier groupe comprenait des douleurs osseuses ou articulaires, des crampes musculaires, des douleurs musculaires, une sensation de nervosité et un manque d'énergie. Le deuxième groupe comprenait des nausées/vomissements, de la diarrhée, des douleurs thoraciques et des maux de tête. Le premier groupe (score médian : ­0,56; du 25e au 75e percentile : ­1, 18 à 0,55) a été indépendamment associé à un temps de récupération plus long (rapport de cotes : 1,62 par unité de différence de score; IC 95 % : 1,23 à 2,12) et à une diminution des scores des composantes physiques (RC : ­0,72; IC 95 % : ­1, 29 à ­0,15) et des scores des composantes psychologiques (RC : ­0,82; IC 95 % : ­1, 48 à ­0,16). Le deuxième groupe n'a pas été associé avec le temps de récupération (RC : 1,24; IC 95 % : 0,97 à 1,58) ni avec le score des composantes physiques (RC : 0,19; IC 95 % : ­0,46 à 0,83) et les scores des composantes psychologiques (RC : ­0,72; IC 95 % : ­1, 50 à 0,06). Limites: Il s'agissait d'une analyze exploratoire d'un petit ensemble de données provenant de deux centers. D'autres études externes sont nécessaires pour valider ces résultats et, ainsi, confirmer nos groupes de symptômes intradialytiques et la généralisabilité de nos résultats. Conclusion: Les symptômes intradialytiques sont corrélés. La présence de certains symptômes intradialytiques peut prolonger le temps de récupération post-dialyze et altérer la qualité de vie des patients.

Pyoderma Gangrenosum After Insertion of a Hemodialysis Catheter: Koebner Phenomenon, Systemic Inflammatory Response Syndrome, and a Delay in Diagnosis.

Rationale: Pyoderma gangrenosum is a rare neutrophilic dermatosis. Misdiagnosis of pyoderma gangrenosum as an infection is not uncommon. Pyoderma gangrenosum can be associated with Koebner phenomenon and rarely results in systemic inflammatory response syndrome and shock. Presenting concerns of the patient: A 61-year-old woman had recently started maintenance hemodialysis, using a tunneled catheter. She was admitted with fever and signs of inflammation at the catheter exit site and along the tunnel. Diagnoses: The initial diagnosis was catheter-related tunnel infection. The exit site broke down into a 5 cm × 5 cm lesion typical of pyoderma, and a new similar lesion developed at a subcutaneous injection site in her abdomen. Clinical diagnosis of pyoderma gangrenosum was made. She remained febrile despite broad antibiotic coverage and catheter removal and developed systemic inflammatory response syndrome (SIRS) that necessitated transfer to intensive care unit. Interventions: She responded well to fluids and intravenous steroids. Viral and bacterial cultures were negative throughout; echocardiography and computed tomography were unrevealing. Insertion of a new hemodialysis catheter was deferred as long as clinically possible, was undertaken while the patient was taking steroids, and was uncomplicated. Outcomes: She remained hemodynamically stable and was discharged after rehabilitation. Her wounds slowly granulated and healed. Steroids were tapered. Teaching points: To our knowledge, this is the first case report of a patient with pyoderma gangrenosum developing at the site of tunneled hemodialysis catheter. Our patient developed SIRS with no evidence of infection. We summarize 11 previous case reports of pyoderma leading to SIRS and responsive to steroids.

Justification: Le pyoderma gangrenosum est une dermatose neutrophile rare que l'on méprend souvent d'abord pour une infection. Cette affection qui peut être associée au phénomène de Koebner entraîne rarement un syndrome de réponse inflammatoire systémique (SRIS) et un choc. Présentation du cas: Une femme de 61 ans qui avait récemment amorcé un traitement d'hémodialyse d'entretien par cathéter tunnelisé. À l'admission, la patiente présentait de la fièvre et des signes d'inflammation au point d'émergence du cathéter et le long du tunnel. Diagnostic: On a d'abord diagnostiqué une infection du tunnel liée au cathéter. Le point d'émergence s'est étendu en une lésion de 5 cm x 5 cm typique du pyoderma et une nouvelle lésion similaire s'est développée sur l'abdomen à un point d'injection sous-cutanée. Un diagnostic clinique de pyoderma gangrenosum a été établi. La fièvre a persisté malgré une antibiothérapie étendue et le retrait du cathéter; la patiente a développé un SRIS qui a nécessité son transfert à l'unité des soins intensifs. Intervention: La patiente a bien répondu à l'administration de liquides et de stéroïdes par voie intraveineuse. Les cultures virales et bactériennes sont demeurées négatives tout au long; l'échocardiographie et la tomodensitométrie étaient non révélatrices. L'insertion d'un nouveau cathéter d'hémodialyse a été reportée aussi longtemps que le permettait l'état clinique de la patiente. La réinsertion a été entreprise alors que la patiente était sous stéroïdes et elle n'a pas entraîné de complications. Résultats: La patiente est restée hémodynamiquement stable et a obtenu son congé après la réinsertion. Les plaies ont granulé et guéri lentement. Les stéroïdes ont été réduits progressivement. Enseignements tirés: À notre connaissance, il s'agit du premier cas rapporté d'une patiente atteinte de pyoderma gangrenosum développé au point d'émergence d'un cathéter d'hémodialyse tunnelisé. Notre patiente a développé un SRIS sans signe d'infection. Nous résumons 11 cas précédents de pyoderma ayant entraîné un SRIS et ayant répondu aux stéroïdes.

Red blood cell transfusion and increased length of storage are not associated with deep vein thrombosis in medical and surgical critically ill patients: a prospective observational cohort study.

INTRODUCTION: With prolonged storage times, cell membranes of red blood cells (RBCs) undergo morphologic and biochemical changes, termed 'RBC storage lesions'. Storage lesions may promote inflammation and thrombophilia when transfused. In trauma patients, RBC transfusion was an independent risk factor for deep vein thrombosis (DVT), specifically when RBC units were stored > 21 days or when 5 or more units were transfused. The objective of this study was to determine if RBC transfusions or RBC storage age predicts incident DVT in medical or surgical intensive care unit (ICU) patients. METHODS: Using a database which prospectively enrolled 261 patients over the course of 1 year with an ICU stay of at least 3 days, we analyzed DVT and RBC transfusions using Cox proportional hazards regression. Transfusions were analyzed with 4 thresholds, and storage age using 3 thresholds. DVTs were identified by twice-weekly proximal leg ultrasounds. Multivariable analyses were adjusted for 4 significant DVT predictors in this population (venous thrombosis history, chronic dialysis, platelet transfusion and inotropes). RESULTS: Of 261 patients, 126 (48.3%) had at least 1 RBC transfusion; 46.8% of those transfused had ≥ 5 units in ICU. Patients receiving RBCs were older (68.8 vs 64.1 years), more likely to be female (47.0 vs 30.7), sicker (APACHEII 26.8 vs 24.4), and more likely to be surgical (21.4 vs 8.9) (P < 0.05). The total number of RBCs per patient was 1-64, mean was 6.3 (SD 7.5), median was 4 (IQR 2,8). In univariate analyses, there was no association between DVT and RBC exposure (1 day earlier, 3 days earlier, 7 days earlier, or ever) or RBC storage (≤ 7 or > 7 days, ≤ 14 or > 14 days, ≤ 21 or > 21 days). Among patients transfused, no multivariable analyses showed that RBC transfusion or storage age predicted DVT. Trends were counter to the hypothesis (e.g., RBC storage for ≤ 7 days suggested a higher DVT risk compared to > 7 days (HR 5.3; 95% CI 1.3-22.1). CONCLUSIONS: We were unable to detect any association between RBC transfusions or prolonged red cell storage and increased risk of DVT in medical or surgical ICU patients. Alternate explanations include a lack of sufficient events or patients' interaction, between patient groups, a mixing of red cell storage times creating differential effects on DVT risk, and unmeasured confounders.

Nephrologist Views Regarding Cannabinoid Use in Advanced Chronic Kidney Disease and Dialysis: A Survey.

CONTEXT: The efficacy and safety of cannabinoids to treat symptoms in individuals with kidney disease is uncertain. OBJECTIVES: We sought to elicit Canadian nephrologists' views regarding the use and study of cannabinoids in patients with kidney disease in an Internet-based survey of Canadian of Society of Nephrology members treating adult patients with kidney disease including dialysis. METHODS: The degree to which respondents supported the use or study of cannabinoids for symptoms common in kidney disease was assessed using a modified Likert scale ranging from 1 to 7 (anchored at 1-definitely would not and 7-being definitely would). Participants were asked their degree of support for cannabinoid use in clinical practice and for randomized controlled trials examining cannabinoids for anxiety, depression, restless legs syndrome, itchiness, fatigue, chronic pain, decreased appetite, nausea/vomiting, sleep disorder, and others. Multilevel multivariable linear regression was used to identify independent predictors of the degree of support. RESULTS: There were 151 (43.4%) responses from 348 eligible participants. One hundred twenty-four (82%) previously cared for patients using prescribed cannabinoids by other providers, and 29 (19%) had previously prescribed cannabinoids themselves. One hundred thirty-seven (91%) had previously cared for patients using nonprescription cannabinoids, which were used most commonly recreationally (88.3%), for chronic pain (73.7%) or for anxiety (52.6%). Respondents supported the use of cannabinoids (mean score >5) for each symptom in the setting of refractory symptoms. Similarly, respondents supported enrolling patients for trials for all symptoms (mean scores >5). CONCLUSION: Nephrologists broadly support the use and study of cannabinoids for symptoms in patients with kidney disease.

Comparing Renal Replacement Therapy Modalities in Critically Ill Patients With Acute Kidney Injury: A Systematic Review and Network Meta-Analysis.

OBJECTIVES: To compare different modalities of renal replacement therapy in critically ill adults with acute kidney injury. DATA SOURCES: We searched Medline, PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from inception to 25 May, 2020. We included randomized controlled trials comparing the efficacy and safety of different renal replacement therapy modalities in critically ill patients with acute kidney injury. STUDY SELECTION: Ten reviewers (working in pairs) independently screened studies for eligibility, extracted data, and assessed risk of bias. DATA EXTRACTION: We performed random-effects frequentist network meta-analyses and used the Grading of Recommendations, Assessment, Development, and Evaluation approach to assess certainty of evidence. The primary analysis was a four-node analysis: continuous renal replacement therapy, intermittent hemodialysis, slow efficiency extended dialysis, and peritoneal dialysis. The secondary analysis subdivided these four nodes into nine nodes including continuous veno-venous hemofiltration, continuous veno-venous hemodialysis, continuous veno-venous hemodiafiltration, continuous arterio-venous hemodiafiltration, intermittent hemodialysis, intermittent hemodialysis with hemofiltration, slow efficiency extended dialysis, slow efficiency extended dialysis with hemofiltration, and peritoneal dialysis. We set the minimal important difference threshold for mortality as 2.5% (relative difference, 0.04). DATA SYNTHESIS: Thirty randomized controlled trials (n = 3,774 patients) proved eligible. There may be no difference in mortality between continuous renal replacement therapy and intermittent hemodialysis (relative risk, 1.04; 95% CI, 0.93-1.18; low certainty), whereas continuous renal replacement therapy demonstrated a possible increase in mortality compared with slow efficiency extended dialysis (relative risk, 1.06; 95% CI, 0.85-1.33; low certainty) and peritoneal dialysis (relative risk, 1.16; 95% CI, 0.92-1.49; low certainty). Continuous renal replacement therapy may increase renal recovery compared with intermittent hemodialysis (relative risk, 1.15; 95% CI, 0.91-1.45; low certainty), whereas both continuous renal replacement therapy and intermittent hemodialysis may be worse for renal recovery compared with slow efficiency extended dialysis and peritoneal dialysis (low certainty). Peritoneal dialysis was probably associated with the shortest duration of renal support and length of ICU stay compared with other interventions (low certainty for most comparisons). Slow efficiency extended dialysis may be associated with shortest length of hospital stay (low or moderate certainty for all comparisons) and days of mechanical ventilation (low certainty for all comparisons) compared with other interventions. There was no difference between continuous renal replacement therapy and intermittent hemodialysis in terms of hypotension (relative risk, 0.92; 95% CI, 0.72-1.16; moderate certainty) or other complications of therapy, but an increased risk of hypotension and bleeding was seen with both modalities compared with peritoneal dialysis (low or moderate certainty). Complications of slow efficiency extended dialysis were not sufficiently reported to inform comparisons. CONCLUSIONS: The results of this network meta-analysis suggest there is no difference in mortality between continuous renal replacement therapy and intermittent hemodialysis although continuous renal replacement therapy may increases renal recovery compared with intermittent hemodialysis. Slow efficiency extended dialysis with hemofiltration may be the most effective intervention at reducing mortality. Peritoneal dialysis is associated with good efficacy, and the least number of complications however may not be practical in all settings. Importantly, all conclusions are based on very low to moderate certainty evidence, limited by imprecision. At the very least, ICU clinicians should feel comfortable that the differences between continuous renal replacement therapy, intermittent hemodialysis, slow efficiency extended dialysis, and, where clinically appropriate, peritoneal dialysis are likely small, and any of these modalities is a reasonable option to employ in critically ill patients.

Impact of haemoglobin and erythropoietin dose changes on mortality: a secondary analysis of results from a randomized anaemia management trial.

BACKGROUND: Anaemia is a common complication of chronic kidney disease. A number of studies have identified an adverse association between haemoglobin (Hgb) variability and mortality. To date, no study has evaluated the impact of Hgb variability on mortality in the setting of a uniform Hgb target and erythropoiesis-stimulating agents (ESA) dosing strategy. METHODS: One hundred and fifty-four haemodialysis (HD) patients from a previous randomized anaemia management study were followed up for up to 6 years. The impact of Hgb variability and ESA dosing parameters on subsequent mortality risk were evaluated. RESULTS: More rapid rises in Hgb (Hgb deflect(pos)) and ESA dose increases were independently associated with mortality in multivariate analysis, whereas more rapid Hgb declines (Hgb deflect(neg)) and ESA dose decreases were not. Each gram per litre per week increase in Hgb deflect(pos) was associated with an adjusted hazard ratio (HR) of 1.23 (1.03-1.48), while for every 1000-unit increase in ESA dose, the adjusted HR was 1.12 (1.01-1.24). Factors associated with positive Hgb deflections included frequency and magnitude of ESA dose changes, baseline Hgb, patient weight and presence of an HD catheter. CONCLUSIONS: Rapid Hgb rises and greater average Eprex dose increases were independently associated with a higher mortality risk in HD patients after adjustment for baseline Hgb and Eprex dose. A randomized controlled trial evaluating different ESA dosing strategies in response to individual patient ESA responsiveness is needed.

The DIalysis Symptom COntrol-Restless Legs Syndrome (DISCO-RLS) Trial: A Protocol for a Randomized, Crossover, Placebo-Controlled Blinded Trial.

BACKGROUND: Restless legs syndrome (RLS) affects approximately 30% of patients with end-stage kidney disease and is associated with impaired sleep and health-related quality of life. Medications used to treat RLS in patients receiving dialysis may have an increased risk of adverse events with dose titration, and residual RLS symptoms are common despite the use of effective treatments. Randomized controlled trials of monotherapy and combination pharmacologic therapy for RLS in hemodialysis are needed. OBJECTIVE: To perform a randomized, crossover, placebo-controlled blinded trial of pharmacologic therapy for RLS in hemodialysis. DESIGN/SETTING: The DIalysis Symptom COntrol-Restless Legs Syndrome (DISCO-RLS) trial is a randomized, crossover, placebo-controlled blinded trial of fixed low-dose pharmacologic therapy in patients receiving hemodialysis in 10 centers across Canada. It uses patient partners in its design, conduct, and reporting. PARTICIPANTS: Adults receiving thrice-weekly hemodialysis for at least 3 months with RLS of at least mild symptoms defined International Restless Legs Syndrome Study Group Rating Scale (IRLS) of 10 or more will enter a double placebo run-in period to exclude nonadherent participants and those unable to tolerate double placebo. Seventy-two participants who completed the run-in period will be randomized to 1 of 8 treatment sequences based on modeling with 4 treatment periods. METHODS: Each treatment period lasts 4 weeks and consists of ropinirole 0.5 mg daily and gabapentin 100 mg daily, both together or neither with a double dummy placebo control for each treatment. The primary outcome is the difference in change scores of the IRLS between study treatments. Secondary outcomes are the differences in change scores of the Restless Legs Syndrome-6 Scale, patient global impression, 5-level EQ-5D version, and safety outcomes. RESULTS: This randomized, crossover, placebo-controlled blinded trial will evaluate the efficacy and safety of fixed low-dose combination of ropinirole and gabapentin in patients receiving hemodialysis with RLS. LIMITATIONS: Patients with chronic kidney disease not on dialysis, kidney transplant recipients and those receiving peritoneal dialysis or home hemodialysis are not included. The intervention's long term safety and efficacy including the risk of augmentation is not captured. CONCLUSION: This randomized crossover placebo controlled blinded trial will evaluate the efficacy and safety of fixed low-dose combination ropinirole and gabapentin in patients receiving hemodialysis with RLS. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03806530).

CONTEXTE: Le syndrome des jambes sans repos (SJSR) touche environ 30 % des patients atteints d'insuffisance rénale terminale (IRT) et est associé à des troubles du sommeil et à des altérations de la qualité de vie. Les médicaments employés pour traiter le SJSR chez les patients dialysés pourraient présenter un risque accru d'effets indésirables avec un ajustement de la dose, et les symptômes résiduels du SJSR sont fréquents malgré l'utilisation de traitements efficaces. Des essais contrôlés à répartition aléatoire examinant des traitements pharmacologiques en monothérapie ou en combinaison chez les patients hémodialysés sont nécessaires. OBJECTIF: Procéder à un essai croisé, en aveugle, réparti aléatoirement et contrôlé par placébo examinant un traitement pharmacologique contre le SJSR en contexte d'hémodialyse. CONCEPTION: DISCO-RLS (DIalysis Symptom COntrol-Restless Legs Syndrome) est un essai croisé, en aveugle, réparti aléatoirement et contrôlé par placébo examinant une faible dose fixe d'un médicament administré à des patients hémodialysés. L'essai fait appel à des patients-partenaires pour sa conception, sa conduite et ses rapports. CADRE: Dix centres à travers le Canada. SUJETS: Des adultes hémodialysés trois fois par semaine depuis plus de trois mois et présentant au moins des symptômes légers de SJSR, tels que définis par un score de 10 (score IRLS) ou plus sur l'échelle d'évaluation du groupe international d'étude sur le SJSR seront examinés lors d'une période de rodage à double placébo. Cette dernière permettra d'exclure les patients non adhérents et ceux qui ne tolèrent pas le double placébo. Parmi les patients qui complèteront la période de rodage, soixante-douze seront répartis aléatoirement dans une des huit séquences de traitement en fonction d'une modélisation avec quatre périodes de traitement. MESURES: Le principal résultat est l'observation d'une différence entre les traitements à l'étude dans les variations du score IRLS par rapport aux valeurs initiales. Les résultats secondaires incluent des différences dans les variations de scores sur l'échelle du SJSR (Restless Legs Syndrome-6 Scale), dans l'impression générale du patient, dans les résultats de la version à 5 niveaux du EQ-5D et dans les résultats d'innocuité. MÉTHODOLOGIE: Chaque période de traitement dure quatre semaines et consiste en l'administration quotidienne de 0,5 mg de ropinirole et de 100 mg de gabapentine, les deux ensembles ou aucun des deux, avec un double placébo comme témoin pour chaque traitement. LIMITES: Les patients non dialysés atteints de néphropathies chroniques, les receveurs d'une greffe rénale et les patients traités par dialyse péritonéale ou par hémodialyse à domicile sont exclus. L'efficacité et l'innocuité de l'intervention à long terme ne sont pas prises en compte. CONCLUSION: Cet essai croisé, en aveugle, réparti aléatoirement et contrôlé par placébo évaluera l'efficacité et l'innocuité d'une combinaison de ropinirole et de gabapentine à faible dose fixe chez les patients hémodialysés atteints du SJSR. ENREGISTREMENT DE L'ESSAI: ClinicalTrials.gov (NCT03806530).

Single Questions for the Screening of Anxiety and Depression in Hemodialysis.

BACKGROUND: Depression and anxiety are common and underrecognized in end-stage renal disease (ESRD), are associated with poor outcomes and reduced health-related quality of life, and are potentially treatable. Simple, accurate screening tools are needed. OBJECTIVE: We examined the operating characteristics of single questions for anxiety and depression from the Edmonton Symptom Assessment System (ESAS) in hemodialysis. DESIGN: Cross-sectional study. SETTING: Two outpatient hemodialysis units (1 tertiary, 1 community) in Hamilton, Canada. PATIENTS: Adult prevalent hemodialysis patients. MEASUREMENTS: ESAS and Hospital Anxiety and Depression Scale (HADS). METHODS: Participants were asked the degree to which they experienced anxiety and depression using the ESAS. ESAS single questions for anxiety and depression were compared with the reference standard of the HADS using dialysis population specific cutoffs (HADS anxiety subscale ≥6 and HADS depression subscale ≥7). Logistic regression was used to create receiver operating characteristics (ROC) curves. RESULTS: We recruited 50 participants with a mean age of 64 (SD = 12.4) years, of whom 52% were male and 96% were on ≥3× weekly hemodialysis. Using the reference standards, 28 (56%) had a diagnosis of anxiety and 27 (54%) had a diagnosis of depression. Areas under the ROC curves were 0.83 for anxiety and 0.81 for depression using ESAS scores of ≥2. LIMITATIONS: Sample size and the lack of a reference gold standard. CONCLUSIONS: The ESAS single questions for anxiety and depression have reasonable discrimination in a hemodialysis population. The use of more complex and time-consuming screening instruments could be reduced by adopting the ESAS questions for anxiety and depression in hemodialysis.

CONTEXTE: La dépression et l'anxiété sont fréquentes quoique peu reconnues chez les patients souffrant d'insuffisance rénale terminale (IRT). Ces troubles sont associés à une évolution défavorable de la maladie et à une diminution de la qualité de vie liée à l'état de santé. Cependant, ils sont potentiellement traitables. Des outils de détection simples et précis sont requis. OBJECTIF: Nous avons évalué la fonction d'efficacité de questions uniques sur l'anxiété et la dépression provenant du Système d'évaluation des symptômes d'Edmonton (ESAS) en contexte d'hémodialyse. TYPE D'ÉTUDE: Étude transversale. CADRE: Deux unités d'hémodialyse ambulatoire (une en soins tertiaires, une en milieu communautaire) à Hamilton, au Canada. SUJETS: Des patients adultes hémodialysés. MESURES: L'ESAS et l'Échelle d'anxiété et de dépression en milieu hospitalier (HADS). MÉTHODOLOGIE: Nous avons demandé aux participants, par l'entremise de l'ESAS, dans quelle mesure ils éprouvaient de l'anxiété et de la dépression. Les questions uniques de l'ESAS sur l'anxiété et la dépression ont été comparées à l'étalon de référence de la HADS en utilisant les seuils spécifiques à une population dialysée (sous-échelle de la HADS pour l'anxiété ≥ 6 et sous-échelle de la HADS pour la dépression ≥ 7). Une régression logistique a été utilisée pour établir les courbes de fonction d'efficacité de l'observateur (courbes ROC). RÉSULTATS: Nous avons recruté 50 patients (52 % d'hommes) âgés de 64 ans en moyenne (écart-type : 12,4 ans). La plupart des sujets (96 %) étaient dialysés au moins trois fois par semaine. Selon l'étalon de référence, 28 patients (56 %) vivaient de l'anxiété et 27 (54 %) souffraient de dépression. La surface sous la courbe ROC était de 0,83 pour l'anxiété et de 0,81 pour la dépression selon les scores ESAS ≥ 2. LIMITES: Le faible échantillon de sujets et le fait que l'étude ne comportait pas d'étalon-or. CONCLUSION: Les questions uniques de l'ESAS sur l'anxiété et la dépression ont discriminé adéquatement dans une population de patients hémodialysés. L'adoption du questionnaire ESAS sur l'anxiété et la dépression avec les patients hémodialysés pourrait limiter le recours à des outils de détection chronophages et complexes.

Screening questions for the diagnosis of restless legs syndrome in hemodialysis.

BACKGROUND: Restless legs syndrome (RLS) is common in end-stage renal disease and is associated with reduced health-related quality of life. Simple and accurate screening instruments are needed since RLS is underdiagnosed and treatable. We examined the operating characteristics of screening questions and a disease-specific measurement tool for the diagnosis of RLS in hemodialysis. METHODS: We conducted a cohort study of prevalent adult hemodialysis patients in Hamilton, Canada. The diagnosis of RLS was made using the 2012 Revised International Restless Legs Syndrome Study Group (IRLSSG) criteria. All participants received three screening instruments: (i) a single screening question for RLS derived from a nondialysis population; (ii) a single question from the Edmonton Symptom Assessment System (ESAS); and (iii) the IRLSSG Rating Scale (IRLS). All instruments were compared with the reference standard using logistic regression from which receiver operating characteristics curves were generated. Cutoffs associated with maximum performance were identified. RESULTS: We recruited 50 participants with a mean (SD) age of 64 (12.4) years, of whom 52% were male and 92% were on three times weekly hemodialysis. Using the reference standard, 14 (28%) had a diagnosis of RLS. The single screening question for RLS had an area under the receiver operating curve (AUROC) of 0.72 with a sensitivity of 85.7% and specificity of 58.3%. An ESAS cutoff of ≥1 had the highest AUROC at 0.65 with a sensitivity of 79% and specificity of 56%. An IRLS cutoff of ≥20 had the highest AUROC at 0.75 with a sensitivity of 71% and specificity of 81%. CONCLUSION: IRLS had better specificity than the single question or ESAS for the diagnosis of RLS.

Venous thromboembolism and bleeding in critically ill patients with severe renal insufficiency receiving dalteparin thromboprophylaxis: prevalence, incidence and risk factors.

BACKGROUND: Critically ill patients with renal insufficiency are predisposed to both deep vein thrombosis (DVT) and bleeding. The objective of the present study was to evaluate the prevalence, incidence and predictors of DVT and the incidence of bleeding in intensive care unit (ICU) patients with estimated creatinine clearance <30 ml/min. METHODS: In a multicenter, open-label, prospective cohort study of critically ill patients with severe acute or chronic renal insufficiency or dialysis receiving subcutaneous dalteparin 5,000 IU once daily, we estimated the prevalence of proximal DVT by screening compression venous ultrasound of the lower limbs within 48 hours of ICU admission. DVT incidence was assessed on twice-weekly ultrasound testing. We estimated the incidence of major and minor bleeding by daily clinical assessments. We used Cox proportional hazards regression to identify independent predictors of both DVT and major bleeding. RESULTS: Of 156 patients with a mean (standard deviation) creatinine clearance of 18.9 (6.5) ml/min, 18 had DVT or pulmonary embolism within 48 hours of ICU admission, died or were discharged before ultrasound testing - leaving 138 evaluable patients who received at least one dose of dalteparin. The median duration of dalteparin administration was 7 days (interquartile range, 4 to 12 days). DVT developed in seven patients (5.1%; 95% confidence interval, 2.5 to 10.1). The only independent risk factor for DVT was an elevated baseline Acute Physiology and Chronic Health Evaluation II score (hazard ratio for 10-point increase, 2.25; 95% confidence interval, 1.03 to 4.91). Major bleeding developed in 10 patients (7.2%; 95% confidence interval, 4.0 to 12.8), all with trough anti-activated factor X levels

Attitudes and Opinions of Canadian Nephrologists Toward Continuous Quality Improvement Options.

BACKGROUND AND OBJECTIVES: A shift to holding individual physicians accountable for patient outcomes, rather than facilities, is intuitively attractive to policy makers and to the public. We were interested in nephrologists' attitudes to, and awareness of, quality metrics and how nephrologists would view a potential switch from the current model of facility-based quality measurement and reporting to publically available reports at the individual physician level. DESIGN SETTING PARTICIPANTS AND MEASUREMENTS: The study was conducted using a web-based survey instrument (Online Appendix 1). The survey was initially pilot tested on a group of 8 nephrologists from across Canada. The survey was then finalized and e-mailed to 330 nephrologists through the Canadian Society of Nephrology (CSN) e-mail distribution list. The 127 respondents were 80% university based, and 33% were medical/dialysis directors. RESULTS: The response rate was 43%. Results demonstrate that 89% of Canadian nephrologists are engaged in efforts to improve the quality of patient care. A minority of those surveyed (29%) had training in quality improvement. They feel accountable for this and would welcome the inclusion of patient-centered metrics of care quality. Support for public reporting as an effective strategy on an individual nephrologist level was 30%. CONCLUSIONS: Support for public reporting of individual nephrologist performance was low. The care of nephrology patients will be best served by the continued development of a critical mass of physicians trained in patient safety and quality improvement, by focusing on patient-centered metrics of care delivery, and by validating that all proposed new methods are shown to improve patient care and outcomes.

CONTEXTE ET OBJECTIFS DE L'ÉTUDE: Une transition vers l'attribution de la responsabilité des résultats des patients au médecin traitant plutôt qu'à l'établissement de soins de santé est un concept attrayant pour les décideurs et le grand public. Notre objectif d'étude était bipartite: d'abord, nous voulions explorer la perception et la connaissance qu'ont les néphrologues des indicateurs de la qualité des soins; ensuite, nous souhaitions prendre connaissance de l'avis des néphrologues sur un éventuel changement de modèle, lequel évalue actuellement la qualité des soins de manière globale plutôt que pour chaque médecin et enfin, sur l'idée que de tels rapports individuels soient accessibles au public. CONCEPTION ET CADRE DE L'ÉTUDE PARTICIPANTS ET MÉTHODOLOGIE: L'étude a été réalisée à l'aide d'un sondage Web (voir l'annexe 1). Une version provisoire du sondage a d'abord été testée auprès de huit néphrologues de partout au Canada. La version définitive du sondage a été envoyée par courriel à 330 néphrologues figurant sur la liste d'envoi de la Société canadienne de néphrologie (SCN). Le taux de réponse global a été de 43%. Des 127 répondants, la grande majorité (80%) travaillait en milieu universitaire et 33% occupait un poste de directeur médical ou de directeur d'unité de dialyse. RÉSULTATS: Les résultats ont démontré que 89% des néphrologues canadiens s'efforcent déjà d'améliorer les soins prodigués aux patients, et qu'une minorité d'entre eux (29%) ont reçu une formation pertinente. De manière générale, ils se sentent responsables de la qualité des soins et sont réceptifs à l'idée d'inclure des critères d'évaluation plus axés sur les patients. Le taux d'approbation en regard de l'accès libre aux rapports individuels comme une stratégie efficace au plan individuel était de 30%. CONCLUSION: Un faible pourcentage des néphrologues s'est prononcé en faveur de la divulgation publique de rapport faisant état de leur performance individuelle. Les soins prodigués aux patients suivis en néphrologie seront perfectionnés en continuant d'augmenter le nombre de médecins formés en matière d'amélioration de la qualité des soins aux patients et de sécurité, en promouvant des indicateurs de qualité centrés sur les patients, et en vérifiant que toute nouvelle méthode proposée vise foncièrement à améliorer les soins ou les résultats des patients.

Two phosphAte taRGets in End-stage renal disease Trial (TARGET): A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Hyperphosphatemia is common among recipients of maintenance dialysis and is associated with a higher risk of mortality and cardiovascular events. A large randomized trial is needed to determine whether lowering phosphate concentrations with binders improves patient-important outcomes. To inform such an effort we conducted a pilot randomized controlled trial. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a randomized controlled trial of prevalent hemodialysis recipients already receiving calcium carbonate as a phosphate binder at five Canadian centers between March 31, 2014 and October 2, 2014. Participants were randomly allocated to 26 weeks of an intensive phosphate goal of 2.33-4.66 mg/dl (0.75-1.50 mmol/L) or a liberalized target of 6.20-7.75 mg/dl (2.00-2.50 mmol/L) by titrating calcium carbonate using a dosing nomogram. The primary outcome was the difference in the change in serum phosphate from randomization to 26 weeks. RESULTS: Fifty-three participants were randomized to the intensive group and 51 to the liberalized group. The median (interquartile range) daily dose of elemental calcium at 26 weeks was 1800 (1275-3000) mg in the intensive group, and 0 (0-500) mg in the liberalized group. The mean (SD) serum phosphate at 26 weeks was 4.53 (1.12) mg/dl (1.46 [0.36] mmol/L) in the intensive group and 6.05 (1.40) mg/dl (1.95 [0.45] mmol/L) in the liberalized group. Phosphate concentration in the intensive group declined by 1.24 (95% confidence interval, 0.75 to 1.74) mg/dl (0.40 [95% confidence interval, 0.24 to 0.56] mmol/L) compared with the liberalized group. There were no statistically significant differences between the two groups in the risk of hypercalcemia, hypocalcemia, parathyroidectomy, or major vascular events. CONCLUSIONS: It is feasible to achieve and maintain a difference in serum phosphate concentrations in hemodialysis recipients by titrating calcium carbonate. A large trial is needed to determine if targeting a lower serum phosphate concentration improves patient-important outcomes.

Thromboembolism and anticoagulant management in hemodialysis patients: a practical guide to clinical management.

The need for anticoagulation in dialysis patients is common and the incidence of venous thromboembolism (VTE) and atrial fibrillation in this population is high. While direct data are lacking on the management of anticoagulation in dialysis patients, careful weighing of risks and benefits on the basis of evidence from other populations is crucial. VTE should be managed with adjusted dose warfarin for most patients. Placement of an inferior vena cava filter is a reasonable option for those patients with unacceptable bleeding risks. Studies are ongoing to assess the safety of some low-molecular-weight heparins (LMWH), which may potentially be useful for long-term anticoagulation in hemodialysis patients. In atrial fibrillation the available data on risk of bleeding, risk of stroke, and patient preferences should all be taken into account when considering long-term anticoagulation. We have constructed an evidence model to help quantitate the risks and benefits for an individual patient. The impact of dialysis on risk of bleeding is such that the risk of bleeding will outweigh the benefit in many patients, and anticoagulation will not be used: in some of these patients aspirin therapy may be an alternative. Finally, in the area of prevention of graft and access thrombosis, some randomized controlled trials are available, but none have to date shown benefit from anticoagulation for primary or secondary prevention of thrombosis, and the risk of bleeding in these studies was high.

Anticoagulant prophylaxis in special populations with an indwelling epidural catheter or renal insufficiency.

The prevention of deep venous thrombosis in postoperative patients who have an indwelling epidural catheter and patients with impaired renal function is a frequently encountered and challenging clinical management problem. Such patients make up a considerable proportion of patients in a medical-surgical intensive care unit. The management of such patients is problematic because low-molecular-weight heparins, the anticoagulant of choice as thromboprophylaxis for many clinical indications, are generally avoided in such patients. This review focuses on anticoagulant prophylaxis in such patients, including reasonable approaches for using low-molecular-weight heparins as thromboprophylaxis.

Dalteparin thromboprophylaxis for critically ill medical-surgical patients with renal insufficiency.

PURPOSE: Thromboprophylaxis with low-molecular-weight heparin (LMWH) may be more effective than unfractionated heparin but also more likely to bioaccumulate and potentially cause bleeding in patients with renal insufficiency. The objectives of this study were to assess, among medical-surgical patients in the intensive care unit receiving dalteparin 5,000 IU daily for thromboprophylaxis, (1) the relationship between renal dysfunction and LMWH bioaccumulation as measured by trough anti-Xa levels, (2) the relationship between renal dysfunction and risk of bleeding as measured by a surrogate marker (peak anti-Xa levels), and (3) the relationship between anti-Xa levels, bleeding events, and thrombotic events. MATERIALS AND METHODS: In this prospective single-center cohort study, we enrolled patients 18 years or older, expected to stay 72 hours or longer, and with a creatinine clearance 30 mL/min or higher at intensive care unit admission. We administered 5,000 IU dalteparin subcutaneously each day. The main phase 1 objective was to detect bioaccumulation of dalteparin by measuring trough anti-Xa levels (22-23 hours post dalteparin). The main phase 2 objective was to examine the relationship between renal dysfunction and peak anti-Xa levels (4 hours post dalteparin). We recorded creatinine clearance daily and bleeding and thrombotic events, blinded to anti-Xa levels. RESULTS: We enrolled 19 patients aged 62.7 (13.2) years with an APACHE II score of 23.5 (9.4). We measured trough anti-Xa levels on 185 occasions in 19 patients; we measured peak anti-Xa levels on 113 occasions in 11 patients. We identified no bioaccumulation of LMWH in this study, as detected by trough anti-Xa levels. Most peak anti-Xa levels were in the conventional prophylactic range. CONCLUSIONS: When administered in prophylactic doses to critically ill patients with a wide range of calculated creatinine clearances, we found no evidence of bioaccumulation of dalteparin. If dalteparin does not bioaccumulate, it may be an attractive alternative agent for thromboprophylaxis.

Deep venous thrombosis: clinically silent in the intensive care unit.

PURPOSE: The reliability of clinical signs and the physical examination in the evaluation of deep venous thrombosis (DVT) in the critically ill is unknown. The purpose of this study was to determine the diagnostic properties of clinical examination for signs of DVT in a cohort of medical-surgical intensive care unit (ICU) patients using screening compression ultrasonography as a reference standard. MATERIALS AND METHODS: We prospectively included patients older than 18 years with an expected length of ICU stay of more than 72 hours. Patients underwent bilateral lower limb screening compression ultrasound twice weekly and structured physical examination twice weekly by 2 independent trained research coordinators blinded to the ultrasonography results. We classified patients according to 2 methods: method 1, a DVT Risk Stratification System of 3 categories and method 2, a DVT Risk Score, both of which use the history and physical examination to stratify patients for their risk of DVT. RESULTS: We included 239 patients in our study, 32 of whom had DVT based on the results of their compression ultrasound. We excluded 7 patients with DVT on ICU admission and 2 who did not undergo any structured examinations. We matched controls with cases (9:1) based on duration of ICU stay. Cases and controls were then allocated to low, moderate, and high risk strata for DVT. Using method 1, the area under the receiver operating characteristic curve (AUC) was 0.57 (95% CI, 0.33-0.78, P = .01). Using method 2, the AUC was 0.59 (95% CI, 0.42-0.75, P = .02). An AUC of 1.0 indicates an ideal test, and AUC of 0.50 indicates a test with no diagnostic utility. CONCLUSIONS: The history and physical examination for DVT are not useful in detecting lower limb DVT in the ICU.

Thrombocytopenia in medical-surgical critically ill patients: prevalence, incidence, and risk factors.

OBJECTIVE: The purpose of this study is to describe the prevalence, to analyze the incidence and independent risk factors for thrombocytopenia, and to examine the impact of thrombocytopenia developing in the intensive care unit (ICU) on patient outcome in a well-defined cohort of critically ill patients in a medical-surgical ICU. MATERIALS AND METHODS: As part of a prospective cohort study examining the frequency and clinical importance of venous thromboembolism in the ICU, we enrolled consecutive patients older than 18 years expected to be in the ICU for more than 72 hours. Exclusion criteria were an admitting diagnosis of trauma, orthopedic surgery or cardiac surgery, pregnancy, and life support withdrawal. Patients had platelet counts performed as directed by clinical need. We defined thrombocytopenia as a platelet count of less than 150 x 10(9)/L and severe thrombocytopenia as a platelet count of less than 50 x 10(9)/L. Protocol-directed care included routine thromboprophylaxis and twice weekly screening ultrasonography of the legs. Patients were followed to hospital discharge. RESULTS: Of the 261 enrolled patients, 121 (46%, 95% confidence interval [CI], 40%-53%) had thrombocytopenia (62 on ICU admission and 59 acquired during their ICU stay). Patients who developed a platelet count less than 150 x 10(9)/L during their ICU stay had higher ICU and hospital mortality (P = .03 and .005, respectively), required longer mechanical ventilation (P = .05), and were more likely to receive platelets (P < .001), fresh frozen plasma (P = .005), and red blood cell transfusions (P = .004) than patients who did not develop thrombocytopenia. The only independent risk factors for thrombocytopenia developing during the ICU stay were administration of nonsteroidal anti-inflammatory drugs before ICU admission (hazard ratio, 2.8; 95% CI, 1.3-6.0) and dialysis during the ICU stay (hazard ratio, 3.1; 95% CI, 1.2-7.8). Of the 33 patients who underwent 36 tests for heparin-induced thrombocytopenia, none tested positive. CONCLUSIONS: We found that about 50% of the patients admitted to the ICU had at least one platelet count of less than 150 x 10(9)/L during their ICU stay. Patients who developed thrombocytopenia were more likely to die, required longer duration of mechanical ventilation, and were more likely to require blood product transfusion. Heparin-induced thrombocytopenia was frequently suspected but did not develop in these critically ill patients.

Prophylaxis of Thromboembolism in Critical Care (PROTECT) Trial: a pilot study.

PURPOSE: There is no randomized trial comparing low-molecular weight heparin (LMWH) and unfractionated heparin (UFH) for thromboprophylaxis in medical-surgical ICU patients. The primary objective of this randomized pilot study on LMWH vs UFH was to assess the feasibility of conducting a large randomized trial with respect to timely enrollment and blinded study drug administration, practicality of twice-weekly lower limb ultrasounds to screen for deep venous thrombosis, LMWH bioaccumulation and dose adjustment in renal insufficiency, and recruitment rates for a future trial in medical-surgical intensive care unit (ICU) patients. Its additional goals were to evaluate the suitability of the exclusion criteria and to document the range of research activities that precede accrual of patients into a trial to plan multisite management. MATERIALS AND METHODS: By computerized telephone randomization, we allocated 129 medical-surgical ICU patients to treatment with dalteparin 5,000 IU QD SC or that with UFH 5,000 IU BID SC. Within each clinical center, only the study pharmacist was not blinded. We performed bilateral lower limb compression ultrasounds within 48 hours of ICU admission, twice weekly, on suspicion of deep venous thrombosis, and 7 days after ICU discharge. Research coordinators and investigators at 7 centers reported the time they engaged in all research activities before the first patient was randomized. RESULTS: Timely complete study drug administration occurred after enrollment. More than 99% of scheduled doses were administered in a blinded fashion. Scheduled ultrasounds were performed without exception. No bioaccumulation of dalteparin was observed when creatinine clearance decreased to lower than 30 mL/min. Average recruitment was 2 patients/center per month before the study exclusion criteria were modified. Study startup activities required, on average, 65.5 hours of combined investigator and research coordinator time at each center. Careful examination of the accrual in the pilot study led to a reexamination of the Prophylaxis of Thromboembolism in Critical Care Trial (PROTECT) study exclusion criteria. CONCLUSIONS: This pilot study suggests that a multicenter randomized clinical trial comparing LMWH with UFH in critically ill medical-surgical patients is feasible. Pilot studies can improve the design of larger trials and may enhance successful timely completion.

The Safety of Eplerenone in Hemodialysis Patients: A Noninferiority Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Mineralocorticoid receptor antagonism reduces morbidity and mortality in patients with heart failure, but the safety of these drugs in patients receiving dialysis is unclear. This study evaluated whether hyperkalemia and/or hypotension limited the use of eplerenone, a selective mineralocorticoid receptor antagonist, in hemodialysis patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a randomized controlled trial of prevalent patients receiving hemodialysis at five Canadian centers. Participants were randomly allocated to 13 weeks of eplerenone titrated to 50 mg daily (n=77) or a matching placebo (n=77). The primary outcome was permanent discontinuation of the drug because of hyperkalemia or hypotension. Secondary outcomes included hyperkalemia, hypotension, and cardiovascular events. RESULTS: Seventy-five eplerenone-treated patients and 71 placebo-treated patients were included in the per protocol population. The primary outcome occurred in three patients (4.0%) in the eplerenone group and two (2.8%) in the placebo group, for an absolute risk difference of 1.2 percentage points (95% confidence interval, -4.7 to 7.1 percentage points). Eplerenone was interpreted as noninferior to placebo with respect to the primary outcome (i.e., a discontinuation rate for these reasons >10% was excluded). In the eplerenone group, nine patients (11.7%) developed hyperkalemia (potassium level >6.5 mEq/L), compared with two patients (2.6%) in the placebo group (relative risk, 4.5; 95% confidence interval, 1.0 to 20.2). There was no significant effect on predialysis or postdialysis BP. CONCLUSION: Eplerenone increased the risk of hyperkalemia but did not result in an excess need to permanently discontinue the drug. Further trials are required to determine whether mineralocorticoid receptor antagonism improves cardiovascular outcomes in patients receiving long-term dialysis.