Vitamin D status and treatment in ESKD; links to improved CKD-MBD laboratory parameters in a real-world setting.

INTRODUCTION: Vitamin D insufficiency is common in patients who receive hemodialysis yet there is no clear guidance regarding surveillance or treatment. We hypothesized that increasing 25(OH)D3 levels is associated with lower phosphate, parathyroid hormone (PTH) and alkaline phosphatase (ALP). METHODS: Baseline 25(OH)D3 level was measured in all patients receiving in-centre hemodialysis in June, 2017. Laboratory parameters were measured every 6 (phosphate, calcium) or 12 weeks (25(OH)D3, PTH, ALP) until February, 2021. In September, 2018 a treatment algorithm of 50,000 IU weekly until sufficient, followed by 50,000 IU monthly was suggested. Generalized linear mixed regression models including linear spline effects, a log link function, and random effects were used to examine the impact of increasing 25(OH)D3 levels on calcium, phosphate, ALP and PTH. RESULTS: Of 697 participants, 15% and 57% had vitamin D deficiency (25(OH)D3 < 25 nmol/L) and insufficiency (between 25 and 74 nmol/L). Incorporating up to 7272 observations, increasing 25(OH)D3 was associated with significantly decreasing PTH for 25(OH)D3 levels between 25 and 75 nmol/L regardless of vitamin D treatment. In an interaction model, the negative slope between 25(OH)D3 and PTH remained significant beyond 75 nmol/L in the absence of calcitriol. Increasing 25(OH)D3 was associated with significantly decreasing phosphate for 25(OH)D3 levels between 25 and 75nmol/L regardless of vitamin D treatment, and below 25 nmol/L in values of untreated patients. Calcium increased across the spectrum of 25(OH)D3 regardless of vitamin D treatment. 0.2% of 25(OH)D3 levels exceeded 250 nmol/L and 2.1% of calcium levels exceeded the normal range. CONCLUSIONS: Vitamin D treatment in a real-world setting was safe and associated with lower PTH levels. Whether improved biochemical markers translate to a reduction in.

The Frequency of Routine Blood Sampling and Patient Outcomes Among Maintenance Hemodialysis Recipients.

RATIONALE & OBJECTIVE: Surveillance blood work is routinely performed in maintenance hemodialysis (HD) recipients. Although more frequent blood testing may confer better outcomes, there is little evidence to support any particular monitoring interval. STUDY DESIGN: Retrospective population-based cohort study. SETTING & PARTICIPANTS: All prevalent HD recipients in Ontario, Canada, as of April 1, 2011, and a cohort of incident patients commencing maintenance HD in Ontario, Canada, between April 1, 2011, and March 31, 2016. EXPOSURE: Frequency of surveillance blood work, monthly versus every 6 weeks. OUTCOMES: The primary outcome was all-cause mortality. Secondary outcomes were major adverse cardiovascular events, all-cause hospitalization, and episodes of hyperkalemia. ANALYTICAL APPROACH: Cox proportional hazards with adjustment for demographic and clinical characteristics was used to evaluate the association between blood testing frequency and all-cause mortality. Secondary outcomes were evaluated using the Andersen-Gill extension of the Cox model to allow for potential recurrent events. RESULTS: 7,454 prevalent patients received care at 17 HD programs with monthly blood sampling protocols (n=5,335 patients) and at 8 programs with blood sampling every 6 weeks (n=2,119 patients). More frequent monitoring was not associated with a lower risk for all-cause mortality compared to blood sampling every 6 weeks (adjusted HR, 1.16; 95% CI, 0.99-1.38). Monthly monitoring was not associated with a lower risk for any of the secondary outcomes. Results were consistent among incident HD recipients. LIMITATIONS: Unmeasured confounding; limited data for center practices unrelated to blood sampling frequency; no information on frequency of unscheduled blood work performed outside the prescribed sampling interval. CONCLUSIONS: Monthly routine blood testing in HD recipients was not associated with a lower risk for death, cardiovascular events, or hospitalizations as compared with testing every 6 weeks. Given the health resource implications, the frequency of routine blood sampling in HD recipients deserves careful reassessment.

Routine Laboratory Testing Every 4 Versus Every 6 Weeks for Patients on Maintenance Hemodialysis: A Quality Improvement Project.

RATIONALE & OBJECTIVE: Few data exist revealing how the frequency of routine blood work for patients on maintenance hemodialysis therapy affects patient outcomes and the costs of care. Our objective was to determine the effect of changing the frequency of blood work from 4- to 6-week intervals on the achievement of anemia and chronic kidney disease-mineral and bone disorder (CKD-MBD) targets. STUDY DESIGN: Retrospective interrupted time series from June 1, 2012, to December 31, 2015. SETTING & PARTICIPANTS: Tertiary hospital in Ontario, Canada, that provides maintenance hemodialysis therapy to 350 to 400 adult patients. QUALITY IMPROVEMENT ACTIVITIES: Institution-wide switch of the interval for routine blood work from 4 to 6 weeks on March 24, 2014. OUTCOMES: Achievement of recommended hemoglobin and phosphate level targets. Cost savings attributable to a change in frequency of blood work for hemoglobin, ferritin, iron saturation, calcium, and phosphate comparing 252-day periods under each testing frequency condition. ANALYTICAL APPROACH: Statistical process control to analyze variation in the clinical outcomes. RESULTS: The proportion of patients who achieved hemoglobin (10-12g/dL) and phosphate (2.5-4.6mg/dL) targets remained stable (average of 60% and 46%, respectively), with no measurements beyond 3 standard deviations from the mean. The hemodialysis unit mortality rate also remained stable (average of 2% per month). Reducing blood work frequency to every 6 weeks was associated with a saving of $85 per patient-year, corresponding to a program-wide savings of $35,000. LIMITATIONS: No case-mix adjustment due to use of aggregate hemodialysis unit data, and absence of data for hospitalizations and transfusions limiting assessment of the full cost of patient care. CONCLUSIONS: After switching the frequency of routine blood work from 4- to 6-week intervals, performance on anemia and CKD-MBD targets did not change and the reduction in blood work was associated with laboratory cost savings. Reducing the frequency of blood work may represent an opportunity for hemodialysis providers to devote greater efforts toward other care elements that better improve patient outcomes.

Death and Dialysis Following Discharge From Chronic Kidney Disease Clinic: A Retrospective Cohort Study.

Background: Multidisciplinary care is recommended for patients with advanced chronic kidney disease (CKD). A formalized, risk-based approach to CKD management is being adopted in some jurisdictions. In Ontario, Canada, the eligibility criteria for multidisciplinary CKD care funding were revised between 2016 and 2018 to a 2 year risk of kidney replacement therapy (KRT) greater than 10% calculated by the 4-variable Kidney Failure Risk Equation (KFRE). Implementation of the risk-based approach has led to the discharge of prevalent CKD patients. Objective: The primary objective of this study was to determine the frequency of occurrence of death and KRT initiation in patients discharged from CKD clinic. Design: Retrospective cohort study. Setting: Single center multidisciplinary CKD clinic in Ontario, Canada. Patients: Four hundred and twenty five patients seen at least once in 2013 at the multidisciplinary CKD clinic. Measurements: Outcomes included discharge status, death, re-referral and KRT initiation. Reasons for discharge were recorded. Methods: Outcomes were extracted from available electronic medical records and the provincial death registry between the patient's initial clinic visit in 2013 and January 1, 2020. KFRE-2 scores were calculated using the 4-variable KFRE equation. The hazard rates of death and KRT after discharge due to stable eGFR/low KFRE were compared to patients who remained in the clinic. Results: Of the 425 CKD patients, 69 (16%) and 19 (4%) were discharged to primary care and general nephrology, respectively. Of those discharged, 7 (8%) were re-referred to nephrology or CKD clinic, while only 2 (2%) discharged patients required subsequent KRT. The hazard of mortality was reduced after discharge from the clinic due to stable eGFR/low KFRE (adjusted HR = 0.45 [95% CI, 0.25-0.78, P = .005]). Limitations: Single center, observational retrospective study design and unknown kidney function over time post discharge for most patients. Conclusions: Discharge of low risk patients from multidisciplinary CKD clinic appears feasible and safe, with fewer than 1 in 40 discharged patients subsequently initiated on KRT over the following 7 years.

Contexte: Des soins multidisciplinaires sont recommandés pour les patients atteints d'insuffisance rénale chronique (IRC) de stade avancé. Une approche officielle de gestion de l'IRC, axée sur le risque, est en cours d'adoption dans certaines juridictions. En Ontario, au Canada, les critères d'admissibilité pour le financement des soins multidisciplinaires d'IRC ont été révisés entre 2016 et 2018 en fonction d'un risque supérieur à 10 % d'amorcer une thérapie de remplacement rénal (TRR) dans les 2 ans (risque calculé par l'équation KFRE [Kidney Failure Risk Equation] à 4 variables). La mise en œuvre de cette approche fondée sur le risque a mené au congé des patients prévalents atteints d'IRC. Objectif: L'objectif principal de cette étude était de déterminer la fréquence des décès et de l'amorce d'une TRR chez les patients ayant reçu leur congé de la clinique d'IRC. Conception: Étude de cohorte rétrospective. Cadre: Une clinique multidisciplinaire d'IRC de l'Ontario (Canada). Sujets: 425 patients vus au moins une fois en 2013 à la clinique multidisciplinaire d'IRC. Mesures: L'état de santé au moment du congé, le décès, la réorientation du patient vers la clinique multidisciplinaire et l'initiation d'une TRR comptaient parmi les résultats d'intérêt. Les raisons du congé ont été enregistrées. Méthodologie: Les résultats ont été extraits des dossiers médicaux électroniques disponibles et du registre provincial des décès entre la première visite à la clinique en 2013 et le 1er janvier 2020. Les scores KFRE-2 ont été calculés avec l'équation KFRE à 4 variables. Le taux d'incidence de décès et de TRR suivant un congé motivé par un DFGe stable ou un faible score KFRE a été comparé à celui des patients restés à la clinique. Résultats: Des 425 patients inclus, 69 (16 %) avaient reçu leur congé en soins primaires et 19 (4 %) en néphrologie générale. Parmi les patients sortis, 7 (8 %) ont été réorientés vers une clinique de néphrologie ou d'IRC et seulement 2 (2 %) ont dû éventuellement amorcer une TRR. Un DFGe stable et un score KFRE faible ont contribué à réduire le taux de mortalité après le congé de la clinique (RR corrigé = 0,45 [IC à 95 %: 0,25-0,78; P = 0,005]). Limites: Étude rétrospective observationnelle dans un seul center. La fonction rénale au fil du temps après le congé de l'hôpital était inconnue pour la plupart des patients. Conclusion: Donner leur congé de la clinique multidisciplinaire d'IRC aux patients à faible risque apparaît possible et sûr; moins d'un patient sur 40 ayant dû amorcer une TRR dans les 7 années suivantes.

Independent External Validation and Comparison of Death and Kidney Replacement Therapy Prediction Models in Advanced CKD.

Rationale & Objective: The Kidney Failure Risk Equation (KFRE) is widely used to predict the risk of kidney replacement therapy (KRT) initiation in chronic kidney disease (CKD) stages G3-G5. The new Grams calculator developed for advanced CKD (stage G4+) predicts KRT initiation, cardiovascular events, and death by uniquely incorporating the competing risk of death. We aimed to validate this tool in a stage G4+ cohort for death and KRT. Study Design: Retrospective cohort study. Setting & Participants: 442 patients with CKD stage G4+ (mean ± SD age, 73 ± 12 years; mean ± SD estimated glomerular filtration rate, 20 ± 6.2 mL/min/1.73 m2) who visited the multidisciplinary CKD clinic at Kingston Health Sciences Center in Ontario, Canada. Outcomes & Analytical Approach: Discrimination and calibration were examined for the outcome of death using the 2- and 4-year Grams scores. The 2- and 5-year KFRE and 2- and 4-year Grams scores were compared in terms of discrimination and calibration for KRT. Results: There were 91, 161, and 206 death events and 90, 145, and 159 KRT events in our cohort at 2, 4, and 5 years, respectively. The Grams model demonstrated modest discrimination for death at 4 years (area under the curve [AUC] 0.70; 95% CI, 0.65-0.75) and performed worse at 2 years (AUC, 0.63; 95% CI, 0.57-0.70). It only overpredicted death by approximately 10% across most of the predicted range. Both models had similar discrimination for KRT at 2 years (KFRE AUC, 0.83; 95% CI, 0.78-0.88 and Grams AUC, 0.8; 95% CI, 0.76-0.87), 4 years (Grams AUC, 0.82; 95% CI, 0.77-0.86), and 5 years (KFRE AUC, 0.81; 95% CI, 0.76-0.85). There was excellent calibration for KRT using the 2-year KFRE and Grams values for predicted risk thresholds of ≤15% and using the 5-year KFRE and 4-year Grams values for predicted risk thresholds of ≤20%. At higher risk ranges, KFRE overpredicts and Grams underpredicts the KRT risk. Limitations: This is a single-center study with a primarily White cohort limited by smaller sample sizes at the higher ranges of the predicted risks, particularly for the Grams calculator. Conclusions: The Grams model provides moderately accurate death predictions, and consideration should be given to its incorporation into patient education and advanced care planning. Both the Grams and KFRE models remain clinically useful for determining KRT risks in advanced CKD.

MyTEMP: Statistical Analysis Plan of a Registry-Based, Cluster-Randomized Clinical Trial.

BACKGROUND: Major Outcomes with Personalized Dialysate TEMPerature (MyTEMP) is a 4-year cluster-randomized clinical trial comparing the effect of using a personalized, temperature-reduced dialysate protocol versus a dialysate temperature of 36.5°C on cardiovascular-related death and hospitalization. Randomization was performed at the level of the dialysis center ("the cluster"). OBJECTIVE: The objective is to outline the statistical analysis plan for the MyTEMP trial. DESIGN: MyTEMP is a pragmatic, 2-arm, parallel-group, registry-based, open-label, cluster-randomized trial. SETTING: A total of 84 dialysis centers in Ontario, Canada. PATIENTS: Approximately 13 500 patients will have received in-center hemodialysis at the 84 participating dialysis centers during the trial period (April 3, 2017, to March 1, 2021, with a maximum follow-up to March 31, 2021). METHODS: Patient identification, baseline characteristics, and study outcomes will be obtained primarily through Ontario administrative health care databases held at ICES. Covariate-constrained randomization was used to allocate the 84 dialysis centers (1:1) to the intervention group or the control group. Centers in the intervention group used a personalized, temperature-reduced dialysate protocol, and centers in the control group used a fixed dialysate temperature of 36.5°C. OUTCOMES: The primary outcome is a composite of cardiovascular-related death or major cardiovascular-related hospitalization (defined as a hospital admission with myocardial infarction, congestive heart failure, or ischemic stroke) recorded in administrative health care databases. The key secondary outcome is the mean drop in intradialytic systolic blood pressure, defined as the patients' predialysis systolic blood pressure minus their nadir systolic blood pressure during the dialysis treatment. Anonymized data on patients' predialysis and intradialytic systolic blood pressure were collected at monthly intervals from each dialysis center. ANALYSIS PLAN: The primary analysis will follow an intent-to-treat approach. The primary outcome will be analyzed at the patient level as the hazard ratio of time-to-first event, estimated from a subdistribution hazards model. Within-center correlation will be accounted for using a robust sandwich estimator. In the primary analysis, patients' observation time will end if they experience the primary outcome, emigrate from Ontario, or die of a noncardiovascular cause (which will be treated as a competing risk event). The between-group difference in the mean drop in intradialytic systolic blood pressure obtained during the dialysis sessions throughout the trial period will be analyzed at the center level using an unadjusted random-effects linear mixed model. TRIAL STATUS: The MyTEMP trial period is April 3, 2017, to March 31, 2021. We expect to analyze and report results by 2023 once the updated data are available at ICES. TRIAL REGISTRATION: MyTEMP is registered with the US National Institutes of Health at clincaltrials.gov (NCT02628366). STATISTICAL ANALYTIC PLAN: Version 1.1 June 15, 2021.

CONTEXTE: L'essai MyTEMP (Major Outcomes with Personalized Dialysate Temperature) est un essai clinique randomisé en grappes d'une durée de 4 ans comparant l'effet d'un protocole de dialysat personnalisé à température réduite par rapport au dialysat à 36,5 °C sur les hospitalisations et les décès dus à des problèmes cardiovasculaires. La répartition aléatoire des sujets a été effectuée au niveau du centre de dialyse (ci-après appelé « groupe ¼). OBJECTIFS: Exposer les grandes lignes du plan d'analyse statistique de l'essai MyTEMP. TYPE D'ÉTUDE: MyTEMP est un essai clinique pragmatique ouvert, à deux bras, en groupes parallèles, basé sur un registre, et randomisé en grappes. CADRE: L'essai est mené dans 84 centres de dialyse en Ontario (Canada). SUJETS: On estime qu'environ 13 500 patients auront reçu des soins d'hémodialyse dans les 84 centres de dialyse participants au cours de la période de l'essai (3 avril 2017 au 1er mars 2021; suivi maximal jusqu'au 31 mars 2021). MÉTHODOLOGIE: Les résultats et les données concernant l'identification des patients et leurs caractéristiques initiales seront principalement tirés des bases de données administratives du système de santé ontarien tenues par l'ICES. Une répartition aléatoire restreinte par les covariables a été employée pour classer les 84 centres de dialyse (1:1) dans le groupe d'intervention ou le groupe témoin. Le groupe d'intervention a utilisé un protocole personnalisé de dialysat à température réduite et le groupe témoin un dialysat à température fixe (36,5 °C). RÉSULTATS: Le principal critère d'évaluation est la combinaison d'un décès d'origine cardiovasculaire ou d'une hospitalisation majeure liée à la santé cardiovasculaire (définie comme une hospitalisation pour un infarctus du myocarde, une insuffisance cardiaque congestive ou un AVC ischémique) enregistrée dans les bases de données administratives du système de santé. Le principal critère d'évaluation secondaire est la baisse moyenne de la tension artérielle systolique intradialytique, laquelle est définie comme la tension artérielle systolique du patient avant la dialyse moins la tension artérielle systolique minimale pendant la dialyse. Les données anonymisées sur la tension artérielle systolique initiale et la tension artérielle systolique intradialytique des patients ont été colligées à intervalles mensuels dans chaque centre de dialyse. PLAN D'ANALYSE: L'analyse primaire adoptera une approche fondée sur l'intention de traiter. Le principal critère d'évaluation sera analysé au niveau du patient comme le risque relatif de survenue d'un premier événement, estimé à partir d'un modèle de risques de sous-distribution. La corrélation intracentre sera prise en compte à l'aide d'un robuste estimateur sandwich. Dans l'analyse primaire, le temps d'observation des patients prendra fin s'ils présentent le principal critère d'évaluation, s'ils déménagent hors de l'Ontario ou s'ils décèdent d'une cause non cardiovasculaire (qui sera traitée comme un événement à risque concurrentiel). La différence entre les groupes quant à la baisse moyenne de la tension artérielle systolique intradialytique, obtenue pendant les séances de dialyse tout au long de l'essai, sera analysée au niveau du centre avec un modèle linéaire mixte à effets aléatoires non corrigé. STATUT DE L'ESSAI: L'essai MyTEMP couvre la période du 3 avril 2017 au 31 mars 2021. Nous comptons analyser et rendre compte des résultats d'ici 2023, dès que les données mises à jour seront disponibles à l'ICES. ENREGISTREMENT DE L'ESSAI: MyTEMP est enregistré auprès du National Institute of Health des États-Unis sur clincaltrials.gov (NCT02628366).

Major Outcomes With Personalized Dialysate TEMPerature (MyTEMP): Rationale and Design of a Pragmatic, Registry-Based, Cluster Randomized Controlled Trial.

BACKGROUND: Small randomized trials demonstrated that a lower compared with higher dialysate temperature reduced the average drop in intradialytic blood pressure. Some observational studies demonstrated that a lower compared with higher dialysate temperature was associated with a lower risk of all-cause mortality and cardiovascular mortality. There is now the need for a large randomized trial that compares the effect of a low vs high dialysate temperature on major cardiovascular outcomes. OBJECTIVE: The purpose of this study is to test the effect of outpatient hemodialysis centers randomized to (1) a personalized temperature-reduced dialysate protocol or (2) a standard-temperature dialysate protocol for 4 years on cardiovascular-related death and hospitalizations. DESIGN: The design of the study is a pragmatic, registry-based, open-label, cluster randomized controlled trial. SETTING: Hemodialysis centers in Ontario, Canada, were randomized on February 1, 2017, for a trial start date of April 3, 2017, and end date of March 31, 2021. PARTICIPANTS: In total, 84 hemodialysis centers will care for approximately 15 500 patients and provide over 4 million dialysis sessions over a 4-year follow-up. INTERVENTION: Hemodialysis centers were randomized (1:1) to provide (1) a personalized temperature-reduced dialysate protocol or (2) a standard-temperature dialysate protocol of 36.5°C. For the personalized protocol, nurses set the dialysate temperature between 0.5°C and 0.9°C below the patient's predialysis body temperature for each dialysis session, to a minimum dialysate temperature of 35.5°C. PRIMARY OUTCOME: A composite of cardiovascular-related death or major cardiovascular-related hospitalization (a hospital admission with myocardial infarction, congestive heart failure, or ischemic stroke) captured in Ontario health care administrative databases. PLANNED PRIMARY ANALYSIS: The primary analysis will follow an intent-to-treat approach. The hazard ratio of time-to-first event will be estimated from a Cox model. Within-center correlation will be considered using a robust sandwich estimator. Observation time will be censored on the trial end date or when patients die from a noncardiovascular event. TRIAL REGISTRATION: www.clinicaltrials.gov; identifier: NCT02628366.

CONTEXTE: De petits essais à répartition aléatoire ont montré que l'utilisation d'un dialysat à basse température réduisait le risque d'hypotension intra-dialytique. De même, certaines études observationnelles ont démontré qu'un dialysat à basse température était associé à un plus faible risque de mortalité toute cause ou d'origine cardiovasculaire. Le temps est venu de procéder à un vaste essai à répartition aléatoire comparant les effets d'un dialysat à basse température et à température standard sur les principaux résultats cardiovasculaires. OBJECTIF: Répartir aléatoirement des centres d'hémodialyse ambulatoire pour qu'ils suivent pendant quatre ans (i) un protocole personnalisé de dialysat à basse température ou (ii) un protocole de dialysat à température standard, et tester l'effet sur les hospitalisations et la mortalité attribuables à des événements cardiovasculaires. TYPE D'ÉTUDE: Un essai clinique à répartition aléatoire en grappes. CADRE: Le 1er février 2017, des centres d'hémodialyse de l'Ontario (Canada) ont été répartis aléatoirement en vue d'un essai qui a débuté le 3 avril 2017 et qui se poursuivra jusqu'au 31 mars 2021. PARTICIPANTS: Quatre-vingt-quatre centres d'hémodialyse qui prendront en charge environ 15 500 patients pendant les quatre ans de suivi. INTERVENTION: Les centres d'hémodialyse ont été répartis aléatoirement (1:1) pour offrir (i) un protocole personnalisé de dialysat à température réduite ou (ii) un protocole de dialysat à 36,5°C. Pour le protocole personnalisé, les infirmières règlent la température du dialysat entre 0,5 et 0,9°C sous la température corporelle du patient mesurée avant la dialyse, jusqu'à une température minimale de 35,5°C. PRINCIPAUX RÉSULTATS: Un ensemble d'hospitalisations attribuables à un événement cardiovasculaire majeur (accident ischémique cérébral non fatal, infarctus du myocarde ou insuffisance cardiaque congestive) et de décès d'origine cardiovasculaire consignés dans les bases de données de santé de l'Ontario. PRINCIPALE ANALYSE ENVISAGÉE: L'analyse primaire adoptera une approche fondée sur l'intention de traiter. Un modèle de Cox servira à estimer le rapport de risque du temps écoulé jusqu'au premier événement. La corrélation intra-centre sera prise en compte à l'aide d'un estimateur sandwich robuste. Le temps d'observation sera censuré à la date de fin de l'essai ou au moment d'un décès non lié à un événement cardiovasculaire.

Validation of a Weight Threshold-Based Vancomycin Dosing Protocol for Patients Undergoing Intermittent Hemodialysis.

BACKGROUND: Patients receiving intermittent hemodialysis (IHD) are at high risk of acquiring gram-positive infections, which are often treated with IV vancomycin. Despite frequent use of vancomycin in the IHD setting, there is variability in dosing and monitoring practices among clinicians at the study institution. There is also a paucity of evidence regarding optimal vancomycin dosing to achieve target pre-IHD serum concentration. OBJECTIVES: The primary objective was to compare the percentage of treatment courses with a serum vancomycin concentration between 15 and 20 mg/L, measured before the third IHD session, before and after implementation of a weight threshold-based dosing protocol. The secondary objectives were to compare the percentage of treatment courses with a pre-third IHD vancomycin concentration between 10 and 22 mg/L and the number of vancomycin measurements per treatment day, before and after protocol implementation. METHODS: This quasi-experimental, single-centre study included inpatients and outpatients who underwent IHD and received at least 2 IV doses of vancomycin, with vancomycin being measured in an appropriately drawn sample before the third IHD session. Before protocol implementation, vancomycin dosing was at the clinician's discretion (usual care). After protocol implementation, each patient received a loading dose of 1000, 1500, or 2000 mg and a maintenance dose of 500, 750, or 1000 mg, depending on body weight. RESULTS: The percentage of treatment courses with a pre-third IHD vancomycin concentration between 15 and 20 mg/L was greater after implementation of the protocol than with usual care, but the difference was nonsignificant (44% [8/18] versus 20% [3/15], p = 0.27). However, the percentage of treatment courses with a pre-third IHD vancomycin concentration between 10 and 22 mg/L was significantly higher after protocol implementation (94% [17/18] versus 53% [8/15], p = 0.012). There was no difference in the median number of vancomycin measurements per treatment day before and after protocol implementation (0.133 versus 0.125, p = 0.99). CONCLUSIONS: At the study institution, the likelihood of achieving recommended vancomycin concentration increased (relative to previous practice) after implementation of a simplified vancomycin dosing protocol for patients undergoing IHD.

CONTEXTE: Les patients recevant une hémodialyse intermittente (HDI) présentent un risque élevé de contracter des infections à Gram positif, souvent traitées à l'aide de vancomycine par intraveineuse (IV). Malgré l'utilisation fréquente de la vancomycine dans les environnements d'HDI, les pratiques portant sur le dosage et le suivi varient entre les cliniciens de l'institution où l'étude s'est déroulée. Il existe également peu de données probantes sur la dose optimale de vancomycine permettant d'atteindre la concentration sérique cible avant l'HDI. OBJECTIFS: L'objectif principal visait à comparer le pourcentage de traitements à la vancomycine, dont la concentration sérique se situait entre 15 et 20 mg/L, lors de la mesure prise avant la troisième séance de HDI, avant et après la mise en place d'un protocole de dosage basé sur le poids. Les objectifs secondaires visaient à comparer le pourcentage de traitements, dont la concentration de vancomycine mesurée avant la troisième séance d'HDI était comprise entre 10 et 22 mg/L, et le nombre de mesures de vancomycine par jour de traitement, avant et après la mise en place du protocole. MÉTHODES: Cette étude quasi expérimentale, menée dans un seul centre, comprenait des patients hospitalisés et ambulatoires ayant subi une HDI et reçu au moins deux doses de vancomycine par IV et dont un échantillon prélevé de manière appropriée avant la troisième séance d'HDI a permis de mesurer la vancomycine. Avant la mise en place du protocole, le dosage de vancomycine était laissé à la discrétion du clinicien (soins habituels). Après sa mise en place, chaque patient recevait une dose de charge de 1000, 1500 ou 2000 mg et une dose de maintenance de 500, 750 ou 1000 mg selon sa masse corporelle. RÉSULTATS: Le pourcentage de traitements dont la concentration de vancomycine mesurée avant la troisième séance d'HDI était comprise entre 15 et 20 mg/L était plus élevé après la mise en place du protocole qu'après les soins habituels, mais la différence n'était pas significative (44 % [8/18] contre 20 % [3/15], p = 0,27). Cependant, le pourcentage de traitements dont la concentration de vancomycine mesurée avant la troisième séance d'HDI était comprise entre 10 et 22 mg/L était significativement plus élevé après la mise en place du protocole (94 % [17/18] contre 53 % [8/15], p = 0,012). Le nombre moyen de mesures de vancomycine par traitement n'avait pas varié entre le jour précédant et le jour suivant la mise en place du protocole (0,133 contre 0,125, p = 0,99). CONCLUSIONS: Dans l'institution où l'étude s'est déroulée, la probabilité d'atteindre la concentration de vancomycine recommandée avait augmenté après la mise en place d'un protocole simplifié de dosage de vancomycine pour les patients recevant une HDI comparativement à une pratique antérieure.

Oral intake during hemodialysis: is there an association with intradialytic hypotension?

Oral intake (OI) of food and fluid has been associated with hypotension during hemodialysis (HD). Trials evaluating this relationship are small. The objective of this study was to quantify OI and to examine its association with hypotension during HD. This is a cross-sectional retrospective chart review study of 3 consecutive HD runs (dialysate iCa=1.25 mmol/L) in 126 stable HD patients (n=378). For each run, the calculation for OI=total ultrafiltration-(net weight loss+IV fluids given). Hypotension was defined as a systolic blood pressure of <100 mmHg at any point during the run. The mean age of the patients was 60.9 years, 38.2% were female, 30.2% had diabetes mellitus, and the majority were Caucasian. The mean (SD) OI was 0.27 (0.352) L/run, range -1.061 to 1.901 L/run, with a normal distribution. In bivariate analysis, there was no correlation of OI with systolic blood pressure, diastolic blood pressure, or mean blood pressure (BP), and the mean OI did not differ among runs with hypotension (n=78) compared with uncomplicated runs (p=0.93). Oral intake was not predictive of hypotension in a multiple logistic regression model controlling for vintage, age, sex, BP medications, coronary disease, dialysis day and shift, diabetes mellitus, s-Ca, Na and ultrafiltration profiles, and dialysis temperature, even when the analysis was restricted to runs where the patients reached the prescribed dry weight within 0.1 kg. The results of this study suggest that the mean OI during dialysis is just over 0.25 kg, with some patients consuming several kilograms. The clinical significance of OI is uncertain. We did not find an association between OI and hypotension. It is likely that this association was confounded by failure to achieve the prescribed dry weight in a proportion of patients with a high OI, as well as interventions implemented in response to hypotension in previous runs. For example, patients with previous episodes of low BP are advised to limit OI, are prescribed profiles, and so on. There may be other deleterious effects of high OI including hypertension and cardiac disease. The generalizability of the results of this largely Caucasian study population is a recognized limitation. Further prospective and blinded studies are needed to examine the association between OI and hypotension, the long-term clinical consequences of OI, and to define thresholds for recommended OI during dialysis.

Adequacy of glycemic control in hemodialysis patients with diabetes.

OBJECTIVE: We sought to measure the prevalence of inadequate glycemic control in prevalent hemodialysis patients with diabetes and to examine independent predictors of inadequate glycemic control in these patients. RESEARCH DESIGN AND METHODS: This is a cross-sectional study of prevalent hemodialysis patients with diabetes in southeastern Ontario (n = 100). Data were collected by chart review and interview. The outcome variable was inadequate glycemic control defined as HbA1c (A1C) >0.07. Other measured variables were diabetes type, diabetes duration, diabetes physician, blood glucose monitoring, diabetes medications, BMI, time on dialysis, and other demographic, clinical, and laboratory variables. RESULTS: Fifty-four patients had A1C >0.07. In bivariate analysis, these patients had a longer diabetes duration (23.6 vs. 14.7 years, P < 0.001), higher proportion with insulin use (81.5 vs. 58.7%, P = 0.012), higher proportion with microvascular complications (66.7 vs. 43.5%, P = 0.017), and lower erythropoietin (EPO) dose (7.0 vs. 11.9 x 10(3) units/week, P < 0.01) than patients with adequate glycemic control. There was no difference between the two groups in terms of macrovascular complications (59.3 vs. 65.2%, P = 0.54). In multiple logistic regression controlling for age and diabetes type, the diabetes duration (odds ratio 1.09 [95% CI 1.04-1.15], P < 0.001), EPO dose (0.90 [0.85-0.97], P < 0.01), and blood glucose monitoring (10.06 [1.03-98.74], P = 0.05) were the only significant independent predictors of A1C >0.07. CONCLUSIONS: A high proportion of hemodialysis patients with diabetes had inadequate glycemic control, particularly those with longstanding disease. Patients with inadequate glycemic control had a significantly higher burden of microvascular complications.

Carotid systolic flow time with passive leg raise correlates with fluid status changes in patients undergoing dialysis.

Corrected carotid systolic flow time (CFTc) has been proposed as a measure of volume status in acutely ill patients. This study endeavors to determine whether the change in CFTc with passive leg raise (PLR) maneuver correlates with volume status changes. Dialysis patients at Kingston General Hospital (Kingston, Canada) underwent point-of-care carotid ultrasonography at the beginning and the end of dialysis. With each measurement, 2 values were recorded: the absolute CFTc, and the difference in CFTc before and after the PLR maneuver. A total of 49 measurements were collected during the study period. CFTc changed with PLR by 5±22milliseconds (2.0%) pre-dialysis and by 40±19milliseconds (13.0%) post-dialysis (P<.0001). Incorporating PLR to the CFTc measurement improved the area under the ROC from 0.64 to 0.91. Particularly, in our sample of patients, a 30milliseconds increase in CFTc with PLR predicted the post-dialysis volume state (LR+=11) whereas an increase of less than 20milliseconds argued against it (LR-=0.079). The assessment of CFTc pre- and post-PLR correlates with intravascular volume changes in patients undergoing dialysis. Alternative to the currently available bedside modalities, this technique is non-invasive, objective, simple to perform at the bedside, and reversible with respect to volume challenge.

Apolipoprotein(a) phenotype and lipoprotein(a) level predict peritoneal dialysis patient mortality.

OBJECTIVE: To examine the associations between lipoprotein(a) [Lp(a)] level, apolipoprotein(a) [apo(a)] phenotype, and patient mortality in peritoneal dialysis (PD) patients. DESIGN: Observational prospective study of prevalent PD patients. SETTING: Tertiary-care health sciences center. PATIENTS: 54 prevalent PD patients were followed prospectively for 24 months. MAIN OUTCOME MEASURES: The exposures were Lp(a) level and apo(a) phenotype, designated by the apo(a) isoform size (number of kringle 4 repeats). Outcome was death from any cause. RESULTS: There were 24 deaths in 77.9 patient-years' follow-up. The independent predictors of death in the multivariate survival analysis were age [relative risk (RR) = 1.03, p = 0.23], diabetes (RR = 3.00, p = 0.03), diastolic blood pressure < or = 70 mmHg (RR = 2.94, p = 0.03), serum albumin (RR = 0.87, p < 0.01), and Lp(a) level (RR = 1.004, p < 0.01). There was strong inverse correlation of Lp(a) with apo(a) isoform size (r = -0.62, p < 0.01). With Lp(a) removed from the model, apo(a) isoform size was a significant predictor of death (RR = 0.91, p = 0.0497). CONCLUSIONS: Lipoprotein(a) level and apo(a) phenotype are associated with PD patient mortality. Measurement of Lp(a) level and apo(a) phenotype may be useful in clinical practice to identify patients at high risk for cardiovascular disease. Large prospective studies are needed to determine if a reversal of the increase in Lp(a) level associated with renal disease and dialysis is feasible and beneficial in reducing the risk of cardiovascular disease and mortality.

Polycythemia due to obstructive sleep apnea in a patient on hemodialysis.

Both anemia and sleep disordered breathing are common in patients with dialysis-dependent stage 5 chronic kidney disease. Erythrocytosis resulting from obstructive sleep apnea (OSA) is rare in the general population and has never been described in the hemodialysis population. We present a case of asymptomatic isolated erythrocytosis and elevated serum erythropoietin level in an otherwise well and previously erythropoietin-dependent chronic hemodialysis patient with chronic kidney disease secondary to ischemic nephropathy. There was no history or symptoms of cardio-pulmonary or hepatic diseases nor any relevant family history. Screening work-up for malignancies was negative. The clinical history was highly suggestive of OSA and severe OSA (respiratory disturbance index of 59) was confirmed by polysomnographic studies. Successful treatment of the OSA with continuous positive airway pressure resulted in permanent stabilization of the hemoglobin to levels below 13 g/dL without the need for repeated phlebotomies and in dramatic lowering of serum erythropoietin levels. To our knowledge, this is the first case of OSA mediated erythrocytosis in a dialysis patient documented in the literature.

Quality of sleep in patients with chronic kidney disease.

BACKGROUND: Sleep disorders are common in patients with renal failure on dialysis; however, the prevalence of "poor sleep" in patients with chronic kidney disease (CKD) not yet on dialysis is not known. This study aimed to measure the prevalence of "poor sleep" in CKD patients and to examine the association between quality of sleep and the degree of renal impairment in this population. METHODS: Quality of sleep was measured using the Pittsburgh Sleep Quality Index (PSQI) in 120 prevalent CKD patients. RESULTS: Sixty-three subjects (53%) had "poor sleep" defined as a global PSQI score >5. There was no statistically significant relationship between the global PSQI score and the blood urea nitrogen level (BUN), serum creatinine level or calculated creatinine clearance, but the sleep efficiency component score correlated with BUN (r = 0.19, P = 0.04) and serum creatinine (r = 0.20, P = 0.03). A history of depression was the only independent predictor of "poor sleep" (global PSQI >5). CONCLUSIONS: "Poor sleep" is common in CKD patients. Quality of sleep decreases in the early stages of CKD and does not appear to be associated with the subsequent degree of renal failure. Large prospective longitudinal studies of quality of sleep in CKD patients are needed to confirm the high prevalence of impaired quality of sleep in this population and examine the association between renal function and quality of sleep while controlling for potential confounding variables.

Quality of sleep and health-related quality of life in haemodialysis patients.

BACKGROUND: Sleep complaints are common in haemodialysis patients. In the general population, insomnia impacts negatively on health-related quality of life (HRQoL). The objective of this study was to examine the association between quality of sleep and HRQoL in haemodialysis patients independent of known predictors of HRQoL. METHODS: Quality of sleep was measured using the Pittsburgh Sleep Quality Index (PSQI) and HRQoL was measured using the Medical Outcomes Study 36-item Short Form (SF-36) in 89 haemodialysis patients. RESULTS: Sixty-three (71%) subjects were 'poor sleepers' (global PSQI >5). The SF-36 mental component summary (MCS) and physical component summary (PCS) correlated inversely with the global PSQI score (MCS, r = -0.28, P < 0.01; PCS, r = -0.45, P < 0.01). The PCS score also correlated with age (r = -0.24, P = 0.02), haemoglobin (r = 0.21, P = 0.048) and comorbidity (r = -0.40, P < 0.01), and mean PCS was lower in depressed subjects (26.2 vs 35.9, P = 0.02). Subjects with global PSQI >5 had a higher prevalence of depression, lower haemoglobin and lower HRQoL in all SF-36 domains. The global PSQI score was a significant independent predictor of the MCS and PCS after controlling for age, sex, haemoglobin, serum albumin, comorbidity and depression in multivariate analysis. CONCLUSIONS: Poor sleep is common in dialysis patients and is associated with lower HRQoL. We hypothesize that end-stage renal disease directly influences quality of sleep, which in turn impacts on HRQoL.