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BACKGROUND: Home dialysis patients may be at an increased risk of adverse events after transitional states. The home dialysis virtual ward (HDVW) trial was conducted in Canadian dialysis centers and aimed to evaluate potential care gaps and patient satisfaction during the HDVW. METHODS: The HDVW was a multicenter single-arm trial including peritoneal dialysis and home hemodialysis patients after 4 different events (hospital discharge, medical procedure, antibiotics, completion of training). Telephone-led interviews using a standardized assessment tool were performed over a 2-week period to assess a patient's care and adjust treatment as required. Upon completion, patients were surveyed to evaluate their perceived impact on domains of care using a rating scale; 1 not satisfied to 10 completely satisfied. RESULTS: The HDVW trial included 193 patients with a median number of potential care gaps/interventions of 1 (0-2) per patient. Patients admitted to the HDVW after hospital discharge were at a higher risk of potential gaps in care (OR 2.16, 95% CI 1.29-3.62), while longer dialysis vintage was -associated with a lower number of gaps/interventions (OR 0.97 per year, 95% CI 0.95-0.98). A total of 105/193 (54%) patients completed satisfaction surveys. Patients were highly satisfied with the HDVW (median rating scale score 8, IQR 2) and felt it had a positive impact (rating scale score ≥7) on their overall health, understanding of treatment and access to a nephrologist. CONCLUSION: The HDVW was effective at identifying several potential care gaps, and patients were satisfied across several domains of care. This intervention may be valuable in supporting home dialysis patients during care transitions.

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RATIONALE & OBJECTIVE: Increasing uptake of home hemodialysis (HD) has led to interest in characteristics that predict discontinuation of home HD therapy for reasons other than death or transplantation. Recent reports of practice pattern variability led to the hypothesis that there are patient- and center-specific factors that influence these discontinuations. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Incident home HD patients at 7 centers in Canada between 2000 and 2010. PREDICTOR: Treatment center, case-mix, and process-of-care variables. OUTCOMES: Technique failure (defined as discontinuation of home HD therapy for any reason other than training failure, death, or transplantation) and mortality. ANALYTICAL APPROACH: Regression modeling of technique failure using Cox proportional hazard models adjusting for treatment center and modifiable and nonmodifiable patient-level variables, censored for death and transplantation. RESULTS: The cohort consisted of 579 patients. Mean age was 49.9±14.1 years, 74% were of European ancestry, median dialysis vintage was 1.9 (IQR, 0.6-5.2) years, and 68% used an arteriovenous access. Mean duration of dialysis was 31.2±12.6 hours per week. Unadjusted 1- and 2-year technique survival and overall survival were 90% and 83% and 94% and 87%, respectively. Treating center was a strong predictor of technique failure and mortality, with HRs ranging from 0.37 to 5.11 for technique failure (1 of 6 centers with P<0.05 relative to the reference) and 0.17 to 8.73 for mortality (3 of 6 centers with P<0.05 relative to the reference). With baseline adjustment for center, only older age and more than 3 treatments per week remained significant predictors of technique failure, while no individual-level variables remained as significant predictors of survival. LIMITATIONS: Limited statistical power. CONCLUSIONS: Home HD treating centers may influence technique failure and patient mortality independent of case-mix. The relationship between processes of care and patient outcomes requires further investigation.

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BACKGROUND: Coronary artery calcification (CAC) is highly prevalent among dialysis patients and is associated with increased cardiovascular and all cause mortality. Magnesium (Mg) inhibits vascular calcification in animal and in-vitro studies but whether the same effect occurs in humans is uncertain. METHODS: A single centre cross-sectional study of 80 prevalent peritoneal dialysis (PD) patients; on PD only for a minimum of 3 months. A radiologist blinded to patient status calculated their abdominal aortic calcification (AAC) scores on lateral lumbar spine radiographs, a validated surrogate for CAC. RESULTS: Eighty patients provided informed consent and underwent lumbar spine radiography. The mean serum Mg was 0.8 mmol/L (standard deviation 0.2) and mean AAC score 8.9 (minimum 0, maximum 24). A higher serum Mg level was associated with a lower AAC score (R 2 = 0.06, unstandardized coefficient [B] = -7.81, p = 0.03), and remained after adjustment for age, serum phosphate, serum parathyroid hormone, low-density lipoprotein cholesterol, smoking history, and diabetes (model adjusted R 2 = 0.36, serum Mg and AAC score B = -11.44, p = 0.00). This translates to a 0.1 mmol/L increase in serum Mg being independently associated with a 1.1-point decrease in AAC score. CONCLUSIONS: Our findings suggest that Mg may inhibit vascular calcification. If this association is replicated across larger studies with serial Mg and vascular calcification measurements, interventions that increase serum Mg and their effect on vascular calcification warrant further investigation in the PD population.

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Hyperphosphatemia has been associated with adverse outcomes in patients with end stage kidney disease (ESKD). The purpose of this study was to determine risk factors for hyperphosphatemia in ESKD patients treated with peritoneal dialysis (PD). This information will be used to develop a patient specific phosphate binder application to facilitate patient self-management of serum phosphate. Adult PD patients documented their food, beverage, and phosphate binder intake for three days using a dietitian developed food journal. Phosphate content of meals was calculated using the ESHA Food Processor SQL Software (ESHA Research, Salem, UT, USA). Clinic biochemistry tests and an adequacy assessment (Baxter Adequest program) were done. Univariate logistic regression was used to determine predictors of serum phosphate >1.78 mmol/L. A multivariable logistic regression model was then fit including those variables that achieved a significance level of p < 0.20 in univariate analyses. Sixty patients (38 men, 22 women) completed the protocol; they were 60 ± 17 years old, 50% had a history of diabetes mellitus (DM) and 33% had hyperphosphatemia (PO4 > 1.78 mmol/L). In univariate analysis, the variables associated with an increased risk of hyperphosphatemia with a p-value < 0.2 were male gender (p = 0.13), younger age (0.07), presence of DM (0.005), higher dose of calcium carbonate (0.08), higher parathyroid serum concentration (0.08), lower phosphate intake (0.03), lower measured glomerular filtration rate (0.15), higher phosphate excretion (0.11), and a higher body mass index (0.15). After multivariable logistic regression analysis, younger age (odds ratio (OR) 0.023 per decade, 95% confidence interval (CI) 0.00065 to 0.455; p = 0.012), presence of diabetes (OR 11.40, 95 CI 2.82 to 61.55; p = 0.0003), and measured GFR (OR 0.052 per mL/min decrease; 95% CI 0.0025 to 0.66) were associated with hyperphosphatemia. Our results support that younger age and diabetes mellitus are significant risk factors for hyperphosphatemia. These findings warrant further investigation to determine the potential mechanisms that predispose younger patients and those with DM to hyperphosphatemia.

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Clopidogrel irreversibly binds to the P2Y12 platelet receptor and acts as a potent inhibitor of platelet activation and aggregation. It is currently recommended for the prevention of cardiovascular events in patients with acute coronary syndromes, recent ischemic stroke, and peripheral arterial disease. Clopidogrel is a prodrug requiring hepatic conversion into its active metabolite. In the general population, genetic polymorphisms in the CYP2C19 gene interfering with hepatic conversion and the ABCB1 gene interfering with gut absorption of clopidogrel, account for the large interindividual response to clopidogrel and clopidogrel resistance. Chronic kidney disease (CKD) and ESKD are independent risk factors for clopidogrel resistance; 50-80% of patients with ESKD have high on-treatment residual platelet reactivity when treated with clopidogrel. This may partially explain the abysmal outcomes for patients with kidney disease post coronary intervention. Several assays are used to determine residual on-treatment platelet reactivity; however, their use in tailoring the suitability of clopidogrel treatment in patients with ESKD is unclear. Although clopidogrel decreased cardiovascular events in the general population after acute coronary syndromes and percutaneous intervention in the CURE and CREDO trials, a reanalysis of these studies in patients with CKD (eGFR <60 ml/minute) showed either a reduced or no benefit from clopidogrel treatment. ESKD patients were not represented in these two large trials; this is true for most of the trials that established clopidogrel as an integral part of the therapeutic armamentarium for cardiovascular disease. Furthermore, clopidogrel has been associated with an increased risk of death, death from bleeding, and hospitalization for bleeding in patients with ESKD. In conclusion, current evidence suggests that ESKD patients may not derive the same benefits from clopidogrel therapy as the general population and this therapy may be associated with harm. Properly designed observational studies and randomized controlled trials are needed to establish the role of clopidogrel in patients with ESKD, the use of platelet assays to tailor therapy, and the role of other antiplatelet agents such as prasugrel or ticagrelor in patients who exhibit high on-treatment residual platelet reactivity.

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BACKGROUND: Patients with end-stage renal disease who receive kidney transplants have improved survival and quality of life compared to patients on dialysis. Unfortunately, transplant patients often have a low vitamin D concentration, which has well-known effects on calcium and bone metabolism. The effect of vitamin D on other indicators of transplant function, such as glomerular filtration rate and acute rejection, remains unknown. METHODS/DESIGN: We will conduct a systematic review of vitamin D status and outcomes after kidney transplantation. The primary objective is to assess the relationship between vitamin D and graft function using measured glomerular filtration rate (GFR) or estimated GFR from serum creatinine concentrations. Secondary outcomes will include acute rejection, chronic allograft nephropathy, proteinuria and graft loss. We will search MEDLINE, EMBASE, AMED and CINAHL for randomized and observational studies on adult renal transplant patients who received vitamin D supplementation or had serum vitamin D concentration measured. We will report study quality using the Cochrane Risk Assessment Tool for randomized controlled trials and the Newcastle-Ottawa Scale for observational studies. Quality across studies will be assessed using the GRADE approach. If pooling is deemed appropriate, we will perform meta-analyses using standard techniques for continuous and discrete variables, depending on the outcome. The results of this review may inform guideline development for vitamin D supplementation in renal transplant patients and highlight areas for further research. SYSTEMATIC REVIEW REGISTRATION PROSPERO: CRD42013006464.

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BACKGROUND: Treatment of end stage renal disease patients with short daily hemodialysis has been associated with an improvement in blood pressure. It is unclear from these studies if anti-hypertensive management had been optimized prior to starting short daily hemodialysis. Also, the potential mechanism(s) of blood pressure improvement remain to be fully elucidated. STUDY DESIGN, SETTING AND PARTICIPANTS: We undertook a randomized cross-over trial in adult hypertensive patients with ESRD treated with conventional hemodialysis to determine: 1) if short-daily hemodialysis is associated with a reduction in systolic blood pressure after a 3-month blood pressure optimization period and; 2) the potential mechanism(s) of blood pressure reduction. Blood pressure was measured using Canadian Hypertension Education Program guidelines. Extracellular fluid volume (ECFV) was assessed with bioimpedance. Serum catecholamines were used to assess the sympathetic nervous system. Interleukin-6 (IL-6) and thiobarbituric acid reactive substances (T-BARS) were used as markers of inflammation and oxidative stress respectively. RESULTS: After a 3-month run-in phase in which systolic blood pressure improved, there was no significant difference in pre-dialysis systolic pressure between short-daily and conventional hemodialysis (p = 0.39). However, similar blood pressures were achieved on fewer anti-hypertensive medications with short daily hemodialysis compared to conventional hemodialysis (p = 0.01). Short daily hemodialysis, compared to conventional hemodialysis, was not associated with a difference in dry weight or ECFV (p = 0.77). Sympathetic nervous system activity as assessed by plasma epinephrine (p = 1.0) and norepinephrine (p = 0.52) was also not different. Markers of inflammation (p = 0.42) and oxidative stress (p = 0.83) were also similar between the two treatment arms. CONCLUSIONS: Patients treated with short daily, compared to conventional hemodialysis, have similar blood pressure control on fewer anti-hypertensive medications. The mechanism(s) by which short daily hemodialysis allows for decreased anti-hypertensive medication use remains unclear but effects on sodium balance and changes in peripheral vascular resistance require further study. TRIAL REGISTRATION: ClinicalTrials.gov NCT00759967.

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BACKGROUND: Over 40% of patients with end stage renal disease in the United States were treated with home hemodialysis (HHD) in the early 1970's. However, this number declined rapidly over the ensuing decades so that the overwhelming majority of patients were treated in-centre 3 times per week on a 3-4 hour schedule. Poor outcomes for patients treated in this fashion led to a renewed interest in home hemodialysis, with more intensive dialysis schedules including short daily (SDHD) and nocturnal (NHD). The relative infancy of these treatment schedules means that there is a paucity of data on 'how to do it'. OBJECTIVE: We undertook a systematic survey of home hemodialysis programs in Canada to describe current practice patterns. DESIGN: Development and deployment of a qualitative survey instrument. SETTING: Community and academic HHD programs in Canada. PARTICIPANTS: Physicians, nurses and technologists. MEASUREMENTS: Programmatic approaches to patient selection, delivery of dialysis, human resources available, and follow up. METHODS: We developed the survey instrument in three phases. A focus group of Canadian nephrologists with expertise in NHD or SDHD discussed the scope the study and wrote questions on 11 domains. Three nephrologists familiar with all aspects of HHD delivery reviewed this for content validity, followed by further feedback from the whole group. Multidisciplinary teams at three sites pretested the survey and further suggestions were incorporated. In July 2010 we distributed the survey electronically to all renal programs known to offer HHD according to the Canadian Organ Replacement Registry. We compiled the survey results using qualitative and quantitative methods, as appropriate. RESULTS: Of the academic and community programs that were invited to participate, 80% and 63%, respectively, completed the survey. We observed wide variation in programmatic approaches to patient recruitment, human resources, equipment, water, vascular access, patient training, dialysis prescription, home requirements, patient follow up, medications, and the approach to non-adherent patients. LIMITATIONS: Cross-sectional survey, unable to link variation to outcomes. Competition for patients between HHD and home peritoneal dialysis means that case mix for HHD may also vary between centres. CONCLUSIONS: There is wide variation between programs in all domains of HHD delivery in Canada. We plan further study of the extent to which differences in approach are related to outcomes.

PROBLÉMATIQUE: Au début des années 70, plus de 40% des patients en insuffisance rénale terminale aux États-Unis étaient traités par hémodialyse à domicile (HDD). Cette proportion a décliné rapidement au cours des décennies suivantes, de sorte que le mode de suppléance pour la majorité des patients est maintenant l'hémodialyse 3 fois par semaine à raison de 3 à 4 heures par séance. Les mauvais résultats obtenus avec cette méthode ont renouvelé l'intérêt pour l'HDD, notamment pour les dialyses intensives incluant la dialyse quotidienne courte (DQC) et l'hémodialyse nocturne (HDN). Étant donné leur nouveauté, il y a peu de données sur les façons de faire avec ces modes de suppléance. OBJECTIF: Afin de décrire les pratiques actuelles, nous avons réalisé un questionnaire systématique auprès des programmes d'HDD au Canada. DESIGN: Développement et déploiement d'un outil qualitatif. CADRE: Programmes d'HDD académiques et communautaires au Canada. PARTICIPANTS: Médecins, infirmières et technologues. VARIABLES MESURÉES: Approches pour la sélection des patients, le mode de suppléance, les ressources humaines disponibles et le mode de suivi pour chaque programme. MÉTHODOLOGIE: Nous avons développé un outil en trois phases. Un groupe de discussion composé de néphrologues canadiens ayant une expertise en DQC ou HDN ont échangé sur le contenu de l'étude et ont rédigé des questions sur 11 domaines. Trois néphrologues familiers avec tous les aspects de l'HDD ont révisé la validité des questions, puis ont demandé un nouvel avis à tout le groupe de discussion. Des équipes multidisciplinaires provenant de trois sites ont ensuite évalué le questionnaire et ont apporté des suggestions. En juillet 2010, le questionnaire a été distribué électroniquement à tous les programmes qui offrent l'HDD d'après le Registre canadien des insuffisances et des transplantations d'organes. Les résultats ont été compilés au moyen de méthodes qualitatives ou quantitatives, le cas échéant. RÉSULTATS: 80% des centres académiques et 63% des centres communautaires invités ont répondu au questionnaire. Nous avons observé des variations importantes entre les programmes quant au recrutement des patients, aux ressources humaines, à l'équipement, à l'eau, aux accès vasculaires, à l'entraînement des patients, à la prescription de dialyse, aux exigences du domicile, au suivi des patients, à la médication et à l'approche face aux patients non-adhérents. LIMITATIONS: Étude transversale, incapacité d'associer les variations aux issues cliniques. La compétition entre l'HDD et la dialyse péritonéale pour le recrutement des patients entraîne peut-être une variabilité entre les centres dans la composition des groupes de patients en HDD. CONCLUSIONS: Il y a de grandes variations entre les programmes dans tous les domaines concernant l'HDD au Canada. Nous planifions d'étudier dans le futur jusqu'à quel point ces différences sont reliées aux issues cliniques.

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PURPOSE OF REVIEW: Atrial fibrillation and cardiovascular death are increased in end-stage renal disease (ESRD) patients compared to the general population. The effect of anticoagulant and antiplatelet medications for these indications in ESRD is unclear. However, both classes of medications have been used for the preservation of vascular access. This review explores the risks and benefits of anticoagulant and antiplatelet medications in ESRD. RECENT FINDINGS: ESRD patients with atrial fibrillation have a two and three-fold greater risk of death and stroke, respectively, than ESRD patients without atrial fibrillation. Warfarin does not appear to decrease this risk, and increases the risk of bleeding and vascular calcification. Warfarin also does not appear to be effective for vascular access preservation. In a few large observational studies, antiplatelet agents did not decrease the risk of cardiovascular death, but confounding by indication is likely. Antiplatelet agents do appear to prolong unassisted arteriovenous graft patency, but the effect is modest. SUMMARY: The role of anticoagulant and antiplatelet agents for atrial fibrillation and cardiovascular disease in ESRD remains unclear. Well designed randomized controlled trials to determine the role of anticoagulation in ESRD patients with atrial fibrillation, and anticoagulant and antiplatelet medications in the preservation of central venous catheter function are required.

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Intensive (longer and more frequent) hemodialysis has emerged as an alternative to conventional hemodialysis for the treatment of patients with end-stage renal disease. However, given the differences in dialysis delivery and models of care associated with intensive dialysis, alternative approaches to patient management may be required. The purpose of this work was to develop a clinical practice guideline for the Canadian Society of Nephrology. We applied the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach for guideline development and performed targeted systematic reviews and meta-analysis (when appropriate) to address prioritized clinical management questions. We included studies addressing the treatment of patients with end-stage renal disease with short daily (≥5 days per week, <3 hours per session), long (3-4 days per week, ≥5.5 hours per session), or long-frequent (≥5 days per week, ≥5.5 hours per session) hemodialysis. We included clinical trials and observational studies with or without a control arm (1990 and later). Based on a prioritization exercise, 6 interventions of interest included optimal vascular access type, buttonhole cannulation, antimicrobial prophylaxis for buttonhole cannulation, closed connector devices, and dialysate calcium and dialysate phosphate additives for patients receiving intensive hemodialysis. We developed 6 recommendations addressing the interventions of interest. Overall quality of the evidence was very low and all recommendations were conditional. We provide detailed commentaries to guide in shared decision making. The main limitation was the very low overall quality of evidence that precluded strong recommendations. Most included studies were small single-arm observational studies. Three randomized controlled trials were applicable, but provided only indirect evidence. Published information for patient values and preference was lacking. In conclusion, we provide 6 recommendations for the practice of intensive hemodialysis. However, due to very low-quality evidence, all recommendations were conditional. We therefore also highlight priorities for future research.

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BACKGROUND: Patients treated with conventional hemodialysis (HD) develop disorders of mineral metabolism that are associated with increased morbidity and mortality. More frequent and longer HD has been associated with improvement in hyperphosphatemia that may improve outcomes. STUDY DESIGN: Systematic review and meta-analysis to inform the clinical practice guideline on intensive dialysis for the Canadian Society of Nephrology. SETTING & POPULATION: Adult patients receiving outpatient long (≥5.5 hours/session; 3-4 times per week) or long-frequent (≥5.5 hours/session, ≥5 sessions per week) HD. SELECTION CRITERIA FOR STUDIES: We included clinical trials, cohort studies, case series, case reports, and systematic reviews. INTERVENTIONS: Dialysate calcium concentration ≥1.5 mmol/L and/or phosphate additive. OUTCOMES: Fragility fracture, peripheral arterial and coronary artery disease, calcific uremic arteriolopathy, mortality, intradialytic hypotension, parathyroidectomy, extraosseous calcification, markers of mineral metabolism, diet liberalization, phosphate-binder use, and muscle mass. RESULTS: 21 studies were identified: 2 randomized controlled trials, 2 reanalyses of data from the randomized controlled trials, and 17 observational studies. Dialysate calcium concentration ≥1.5 mmol/L for patients treated with long and long-frequent HD prevents an increase in parathyroid hormone levels and a decline in bone mineral density without causing harm. Both long and long-frequent HD were associated with a reduction in serum phosphate level of 0.42-0.45 mmol/L and a reduction in phosphate-binder use. There was no direct evidence to support the use of a dialysate phosphate additive. LIMITATIONS: Almost all the available information is related to changes in laboratory values and surrogate outcomes. CONCLUSIONS: Dialysate calcium concentration ≥1.5 mmol/L for most patients treated with long and long-frequent dialysis prevents an increase in parathyroid hormone levels and decline in bone mineral density without increased risk of calcification. It seems prudent to add phosphate to the dialysate for patients with a low predialysis phosphate level or very low postdialysis phosphate level until more evidence becomes available.

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BACKGROUND: Anemia secondary to iron deficiency is common in patients with non-dialysis dependent chronic kidney disease (ND-CKD) but it is unclear if oral supplementation is as effective as intravenous (IV) supplementation in re-establishing iron stores. The purpose of this study was to determine if oral Heme Iron Polypeptide (HIP) is as effective as IV iron sucrose in the treatment of iron-deficiency anemia for patients with ND-CKD. METHODS: Forty ND-CKD patients were randomized; 18 to HIP 11 mg orally 3 times per day and 22 to IV iron sucrose 200 mg monthly for 6 months. Baseline clinical and laboratory data were collected for all patients. The primary and secondary outcomes for the study were hemoglobin (Hgb) concentration and iron indices [ferritin and percentage transferrin saturation (TSAT)] at the end of 6 months respectively. Adverse events were also compared. RESULTS: The baseline demographic characteristics and laboratory values were similar for the two groups. After 6 months of treatment, Hb in the HIP group was 117 g/L and 113 g/L in the IV sucrose group (p = 0.37). The TSAT at 6 months was not different between the two groups {p = 0.82}but the serum ferritin was significantly higher in the IV iron sucrose group {85.5 ug/L in HIP and 244 ug/L; p = 0.004}. Overall adverse events were not different between the groups. CONCLUSION: HIP is similar in efficacy to IV iron sucrose in maintaining hemoglobin in ND-CKD patients with no differences in adverse events over 6 months. It is unclear if the greater ferritin values in the IV iron sucrose group are clinically significant. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00318812.

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Increasing hemodialysis frequency from three to six times per week improves left-ventricular mass and health-related quality of life; however, effects on survival remain uncertain. To study this, we identified 556 patients in the International Quotidian Dialysis Registry who received daily hemodialysis (more than five times per week) between 2001 and 2010. Using propensity score-based matching, we matched 318 of these patients to 575 contemporaneous patients receiving conventional (three times weekly) hemodialysis in the Dialysis Outcomes and Practice Patterns Study. All patients had session times of <5 h, and received dialysis in the clinic or hospital setting. Mortality rates between groups were compared using Cox proportional hazards regression. Mean dialysis frequency in the daily group was 5.8 sessions per week. Mean weekly treatment time was 15.7 h for daily and 11.9 h for conventional patients. During 1382 patient-years of follow-up, 170 patients died. Those receiving daily hemodialysis had a significantly higher mortality rate than those receiving conventional hemodialysis (15.6 and 10.9 deaths per 100 patient-years, respectively: hazard ratio 1.6). Similar results were found in prespecified subgroup and sensitivity analyses. Unlike previous studies, we found that in-center daily hemodialysis was not associated with any mortality benefit. Thus, decisions to undertake daily hemodialysis should be based on quality-of-life improvements, rather than on claims of improved survival.

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Atrial fibrillation is prevalent in dialysis patients. Both ischaemic and haemorrhagic stroke are common in patients on dialysis with atrial fibrillation. In the general population, warfarin is highly effective for prophylaxis of ischaemic stroke, and though warfarin use likely increases the risk of intracranial haemorrhage, the absolute increase in risk is small. In the general population, absolute and relative increases in major extracranial bleeding from warfarin use are also both modest. In patients on dialysis, the effectiveness of warfarin as a prophylaxis for ischaemic stroke and its effects on intracranial or extracranial bleeding have not been assessed in randomized trials. Cohort studies vary greatly in their estimates of the magnitude of the increased risk of bleeding from warfarin use. A single cohort study found rates of intracranial haemorrhage in patients on dialysis with atrial fibrillation to be in an order of magnitude that is greater than those in the general population with atrial fibrillation, and that intracranial haemorrhage more than doubled in association with warfarin use. Basic, translational and limited clinical observations also implicate warfarin in the pathogenesis of vascular calcification, which is likely on the causal pathway to patient-important vascular outcomes. Finally, the effect of warfarin on ischaemic stroke in three recent large observational studies has been in the direction of harm, no benefit, and modest, non-statistically significant benefit, respectively. We believe that no clear recommendation can be made between three alternative approaches. It is acceptable to withhold or discontinue warfarin in patients on dialysis, to offer anticoagulants to all dialysis patients without a contraindication whose congestive heart failure, hypertension, age, diabetes and previous stroke or transient ischaemic attack (CHADS(2)) score >1 or 2 and to discuss and individualize prophylaxis on a patient-by-patient basis. Randomized trials of new agents are needed in this area.

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BACKGROUND AND OBJECTIVES: Patients with end stage renal disease (ESRD) are often prescribed antiplatelet medications. However, these patients are also at increased risk of bleeding compared with the general population, and an aim was made to quantify this risk with antiplatelet agents. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A systematic review of the literature (Medline, EMBASE, Cochrane CENTRAL and Google Scholar databases) was done to determine the bleeding risk in ESRD patients prescribed antiplatelet therapy. The secondary outcome was the effect on access thrombosis. All case series, cohort studies and clinical trials were considered if they included ten or more ESRD patients, assessed bleeding risk with antiplatelet agents, and lasted for more than 3 mo. RESULTS: Sixteen studies, including 40,676 patients, were identified that met predefined inclusion criteria. Due to study heterogeneity and weaknesses in methodology, bleeding rates were not pooled across studies. However, the bleeding risk appears to be increased for hemodialysis patients treated with combination antiplatelet therapy. The results are mixed for studies using a single antiplatelet agent. Antiplatelet agents appear to be effective in preventing shunt and central venous catheter thrombosis, but not for preventing thrombosis of arteriovenous grafts. CONCLUSION: The risks and benefits of antiplatelet agents in ESRD patients remain poorly defined. Until a clinical trial addresses this in the dialysis population, individual risk stratification taking into account the increased risk of bleeding should be considered before initiating antiplatelet agents, especially in combination therapy.

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BACKGROUND AND OBJECTIVES: Hyperphosphatemia is an independent risk factor for mortality in ESRD, but factors regulating phosphate clearance on peritoneal dialysis (PD) are incompletely understood. The objective of this study was to test the hypothesis that peritoneal phosphate clearance is better with continuous ambulatory PD (CAPD) as compared with continuous cyclic PD (CCPD) after adjusting for membrane transport status. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this cross-sectional and retrospective study, measurements of peritoneal phosphate clearance of 129 prevalent PD patients were reviewed. Patients were divided according to membrane transport status (high, high average, low average-low categories) and PD modality (CAPD or CCPD). RESULTS: Among high transporters, peritoneal phosphate clearances were comparable in both modalities. However, treatment with CAPD was associated with increased peritoneal phosphate clearance compared with CCPD among high-average transporters (42.4 +/- 11.4 versus 36.4 +/- 8.3 L/wk/1.73 m(2), P = 0.01), and low-average-low transporters (35.6 +/- 5.9 versus 28.9 +/- 11 L/wk/1.73 m(2), P = 0.034). On multivariate linear regression, PD modality, membrane transport category, and peritoneal creatinine clearance, but not Kt/V urea, were independently associated with peritoneal phosphate clearance. CONCLUSIONS: Peritoneal phosphate clearance is determined by PD modality and membrane transport category, suggesting that PD regimes with longer dwell times may help control hyperphosphatemia in lower transporters.

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