Macrocytosis may be associated with mortality in chronic hemodialysis patients: a prospective study

<p>Abstract</p> <p>Background</p> <p>Macrocytosis occurs in chronic hemodialysis (CHD) patients; however, its significance is unknown. The purpose of this study was to establish the prevalence and distribution of macrocytosis, to identify its clinical associations and to determine if macrocytosis is associated with mortality in stable, chronic hemodialysis patients.</p> <p>Methods</p> <p>We conducted a single-centre prospective cohort study of 150 stable, adult CHD patients followed for nine months. Macrocytosis was defined as a mean corpuscular volume (MCV) > 97 fl. We analyzed MCV as a continuous variable, in tertiles and using a cutoff point of 102 fl.</p> <p>Results</p> <p>The mean MCV was 99.1 ± 6.4 fl, (range 66-120 fl). MCV was normally distributed. 92 (61%) of patients had an MCV > 97 fl and 45 (30%) > 102 fl. Patients were not B12 or folate deficient in those with available data and three patients with an MCV > 102 fl had hypothyroidism. In a logistic regression analysis, an MCV > 102 fl was associated with a higher Charlson-Age Comorbidity Index (CACI) and higher ratios of darbepoetin alfa to hemoglobin (Hb), [(weekly darbepoetin alfa dose in micrograms per kg body weight / Hb in g/L)*1000]. There were 23 deaths at nine months in this study. Unadjusted MCV > 102 fl was associated with mortality (HR 3.24, 95% CI 1.42-7.39, P = 0.005). Adjusting for the CACI, an MCV > 102 fl was still associated with mortality (HR 2.47, 95% CI 1.07-5.71, P = 0.035).</p> <p>Conclusions</p> <p>Macrocytosis may be associated with mortality in stable, chronic hemodialysis patients. Future studies will need to be conducted to confirm this finding.</p

Increases in Intravenous Magnesium Use among Hospitalized Patients: An Institution Cross-Sectional Experience

Background: Among hospitalized patients, indications for the measurement of magnesium levels and treatment of hypomagnesemia with intravenous magnesium are not well defined. Recently, there have been reports of worldwide shortages of intravenous magnesium sulphate. Objective: To examine secular trends in the administration of intravenous magnesium on hospital wards at a tertiary care institution. The secondary objective is to identify factors associated with magnesium use among admitted patients. Methods: Retrospective cross-section review of hospitalized patients at a single Canadian tertiary care center. Utilization of non-parental nutrition intravenous magnesium from 2003 to 2013 stratified by hospital ward was examined. In addition, patient level data from select wards (including medical and surgical services) was examined at early and more recent time period (4/2006 versus 4/2013). Results: Among the 248,329 hospitalized patients, intravenous magnesium use increased by 2.86 fold from 2003 to 2013. Not all wards had an increase whereas some had nearly a 10 fold increase in use. In the sample ( n = 769), (adjusting for admission magnesium level, presence of an indication for intravenous magnesium, ward location, comorbidity and demographics) intravenous magnesium administration was higher (25.8 % versus 5.5 %) in 2013 versus 2006 (OR 13.91 (95 % CI, 6.21–31.17, p < 0.001). Despite this increase in intravenous magnesium administration, <3 % of patients were admitted on oral magnesium in 2006 and 2013. For patients receiving intravenous magnesium only a minority were discharged on oral therapy despite low levels. Conclusions: This center has witnessed a considerable increase in the use of in-hospital intravenous magnesium over the last 6 years that cannot be explained for by medical indications. The risks and benefits of this therapy deserve further study. If this change in practice is representative of other North American hospitals, it may be responsible for recent drug shortages

Proportion and Characteristics of US Adults Who May Be Eligible From Additional Blood Pressure Lowering Based on Absolute Risk: Table 1.

BACKGROUND The Systolic Blood Pressure Intervention Trial (SPRINT) and the Heart Outcomes Prevention Evaluation 3 (HOPE-3) trial demonstrated the merits of blood pressure (BP) lowering to reduce cardiovascular events in intermediate to high cardiovascular risk adults. However, the population impact of an absolute risk-based strategy for BP lowering remains unclear. METHODS We examined 3 treatment thresholds using the National Health and Nutrition Examination Survey. First, the JNC8 guideline was used to determine treatment goals. Second, adults with a systolic BP (SBP) of 130 mm Hg and high cardiovascular risk (based on eligibility for SPRINT) were considered eligible for additional BP lowering. Finally, we combined the treatment threshold for high-risk adults with an SBP treatment threshold of 140 mm Hg for intermediate-risk adults that met the eligibility criteria for HOPE-3. RESULTS Under the JNC8 guideline, 78.0% of adults ≥50 years were at target while 22.0% were eligible for additional BP lowering. If an SBP treatment threshold of 130 mm Hg was used for adults at high cardiovascular risk, 31.1% would be eligible for additional BP lowering (an increase of 8.1 million). If an SBP threshold of 140 mm Hg was additionally used for adults at intermediate risk, 31.4% of adults would be eligible for BP lowering (an increase of 8.3 million). The proportion of adults eligible for BP lowering with established coronary artery disease decreased with the risk-based strategies. CONCLUSION An absolute risk treatment strategy would modestly increase the proportion of adults eligible for BP lowering

Targeting the Opioid Pathway for Uremic Pruritus

Background: Patients undergoing hemodialysis or peritoneal dialysis often experience pruritus which is associated with morbidity and mortality. One proposed treatment approach is to target the opioid pathway using either µ-opioid antagonists or κ-opioid agonists. Objective: To review the efficacy of targeting the opioid pathway for pruritus among dialysis patients (uremic pruritus). Design: Systematic review and meta-analysis. Setting/Methods: The systematic review included randomized controlled and randomized crossover trials identified in the MEDLINE, EMBASE, and Cochrane databases (1990 to June 2014) evaluating the efficacy of µ-opioid antagonists or κ-opioid agonists in the treatment of uremic pruritus. Patients: Adult (≥18 years) chronic dialysis patients. Measurements: The primary outcome being evaluated was reduction in itch severity measured on a patient-reported visual analog scale (VAS). Results: Five studies out of 3587 screened articles met the inclusion criteria. Three studies evaluated the efficacy of naltrexone, a µ-opioid antagonist, and 2 studies evaluated the efficacy of nalfurafine, a κ-opioid agonist. Duration of included studies was short, ranging from 2 to 9 weeks. Limitations: Due to the heterogeneity in reporting of outcomes, data from the studies evaluating naltrexone could not be pooled. Pooled analysis, using a random effects model, found that use of nalfurafine resulted in a 9.50 mm (95% confidence interval [CI], 6.27-12.74, P < .001) greater reduction of itch severity (measured on a 100-mm VAS) than placebo in the treatment of uremic pruritus. Conclusions: Nalfurafine holds some promise with respect to the treatment of uremic pruritus among dialysis patients. However, more long-term randomized controlled trials evaluating the efficacy of therapies targeting the opioid pathway for uremic pruritus are required

A Virtual Ward for Home Hemodialysis Patients – A Pilot Trial

Background: Patients with end-stage renal disease (ESRD) have a high rate of hospitalization and are prone to care gaps that may occur during the transition from hospital to home. The virtual ward (VW) is an innovative model that provides short-term transitional care to patients upon hospital discharge. The VW may be an effective intervention to address care gaps. Objectives: The primary objective of the pilot study was to assess the feasibility and practicality of implementing the Home Dialysis VW (HDVW) on a broader scale. Design: The HDVW Pilot Study enrolled home hemodialysis patients following one of four inclusion criteria: 1. Discharge from hospital, 2. Completion of an in-hospital medical procedure, 3. Prescription of an antibiotic, 4. Completion of home hemodialysis training. Patients were followed in the HDVW for 14 days and during this time were assessed serially with a clinician-led telephone interview for one of three transitional care gaps: 1. Requirement for change in hemodialysis prescription, 2. Requirement for coordination of follow-up care, 3. Requirement for medication change. Setting: The study was conducted in Toronto, Ontario, Canada at a quaternary care academic teaching hospital from 2012–2013. Patients: This study included 52 HDVW admissions among 35 patients selected from the existing home hemodialysis program. Measurements: The primary outcome was the identification of the number of care gaps at each HDVW admission. Secondary outcomes included the identification of potential predictors of care gaps and description of clinical adverse events following HDVW admission (readmissions, emergency department visits, unplanned visits to the home hemodialysis in-center). Results: The implementation and execution of the HDVW Pilot Study proved to be technically feasible and practical. A care gap was identified in 35 (67 %) of the HDVW admissions. In total, the cohort experienced 85 care gaps. There were no baseline demographic characteristics predictive of experiencing a care gap. In the total cohort observed for 2912 patient days, there were 9 readmissions, 13 visits to the emergency department, and 7 unplanned visits to the home hemodialysis in-center unit. Limitations: The results of this study are limited by the small study size and single-center experience. Conclusion: The implementation of a virtual ward for home hemodialysis patients is practical, feasible and identifies many care gaps which have the potential to result in subsequent adverse events. A larger, multi-center prospective clinical trial is justified to identify if the HDVW can prevent adverse events among home dialysis patients

A virtual ward for home hemodialysis patients – a pilot trial

Abstract Background Patients with end-stage renal disease (ESRD) have a high rate of hospitalization and are prone to care gaps that may occur during the transition from hospital to home. The virtual ward (VW) is an innovative model that provides short-term transitional care to patients upon hospital discharge. The VW may be an effective intervention to address care gaps. Objectives The primary objective of the pilot study was to assess the feasibility and practicality of implementing the Home Dialysis VW (HDVW) on a broader scale. Design The HDVW Pilot Study enrolled home hemodialysis patients following one of four inclusion criteria: 1. Discharge from hospital, 2. Completion of an in-hospital medical procedure, 3. Prescription of an antibiotic, 4. Completion of home hemodialysis training. Patients were followed in the HDVW for 14 days and during this time were assessed serially with a clinician-led telephone interview for one of three transitional care gaps: 1. Requirement for change in hemodialysis prescription, 2. Requirement for coordination of follow-up care, 3. Requirement for medication change. Setting The study was conducted in Toronto, Ontario, Canada at a quaternary care academic teaching hospital from 2012–2013. Patients This study included 52 HDVW admissions among 35 patients selected from the existing home hemodialysis program. Measurements The primary outcome was the identification of the number of care gaps at each HDVW admission. Secondary outcomes included the identification of potential predictors of care gaps and description of clinical adverse events following HDVW admission (readmissions, emergency department visits, unplanned visits to the home hemodialysis in-center). Results The implementation and execution of the HDVW Pilot Study proved to be technically feasible and practical. A care gap was identified in 35 (67 %) of the HDVW admissions. In total, the cohort experienced 85 care gaps. There were no baseline demographic characteristics predictive of experiencing a care gap. In the total cohort observed for 2912 patient days, there were 9 readmissions, 13 visits to the emergency department, and 7 unplanned visits to the home hemodialysis in-center unit. Limitations The results of this study are limited by the small study size and single-center experience. Conclusion The implementation of a virtual ward for home hemodialysis patients is practical, feasible and identifies many care gaps which have the potential to result in subsequent adverse events. A larger, multi-center prospective clinical trial is justified to identify if the HDVW can prevent adverse events among home dialysis patients

Nonimmunologic Donor-Recipient Pairing, HLA Matching, and Graft Loss in Deceased Donor Kidney Transplantation

Background. In kidney transplantation, nonimmunologic donor-recipient (D-R) pairing is generally not given the same consideration as immunologic matching. The aim of this study was to determine how nonimmunologic D-R pairing relates to independent donor and recipient factors, and to immunologic HLA match for predicting graft loss. Methods. Seven D-R pairings (race, sex, age, weight, height, cytomegalovirus serostatus, and HLA match) were assessed for their association with the composite outcome of death or kidney graft loss using a Cox regression-based forward stepwise selection model. The best model for predicting graft loss (including nonimmunologic D-R pairings, independent D-R factors, and/or HLA match status) was determined using the Akaike Information Criterion. Results. Twenty three thousand two hundred sixty two (29.9%) people in the derivation data set and 9892 (29.7%) in the validation data set developed the composite outcome of death or graft loss. A model that included both independent and D-R pairing variables best predicted graft loss. The c-indices for the derivation and validation models were 0.626 and 0.629, respectively. Size mismatch (MM) between donor and recipient (>30 kg [D 15 cm [D < R]) was associated with poor patient and graft survival even with 0 HLA MM, and conversely, an optimal D-R size pairing mitigated the risk of graft loss seen with 6 HLA MM. Conclusions. D-R pairing is valuable in predicting patient and graft outcomes after kidney transplant. D-R size matching could offset the benefit and harm seen with 0 and 6 HLA MM, respectively. This is a novel finding

Comorbidity Burden at Dialysis Initiation and Mortality: A Cohort Study

Background: A high level of comorbidity at dialysis initiation is associated with an increased risk of death. However, contemporary assessments of the validity and prognostic value of comorbidity indices are lacking. Objectives: To assess the validity of two comorbidity indices and to determine if a high degree of comorbidity is associated with mortality among dialysis patients. Design: Cohort study. Setting: QEII Health Sciences Centre (Halifax, Nova Scotia, Canada). Patients: Incident, chronic dialysis patients between 01 Jan 2006 and 01 Jul 2013. Measurements: Exposure : The Charlson Comorbidity Index (CCI) and End-Stage Renal Disease Comorbidity Index (ESRD-CI) were used to classify individual comorbid conditions into an overall score. Comorbidities were classified using patient charts and electronic records. Outcome : All-cause mortality. Confounders : Patient demographics, dialysis access, cause of ESRD and baseline laboratory data. Methods: Regression coefficients were estimated on the CCI and ESRD-CI. Discrimination for death was assessed using Harrell's c-index. Adjusted Cox proportional hazard models were used to calculate relative hazards and 95 % confidence intervals for each category of the CCI and ESRD-CI. Results: The cohort consisted of 771 ESRD patients from 01 Jan 2006 to 01 Jul 2013. Most were male (62 %) and Caucasian (91 %). The cohort had a high proportion of diabetes (48 %), history of previous myocardial infarction (31 %) and heart failure (22 %). Regression coefficients on the CCI and ESRD-CI were 0.55 and 0.52, respectively. The c -index, for the prediction of death, was 0.61 for the CCI and 0.63 for the ESRD-CI. ESRD-CI scores of 4, 5 and ≥6 were associated with a similar mortality risk (adjusted relative hazard of 1.95, 1.89 and 1.99, respectively). There was a small increased mortality risk for CCI scores of 4, 5 and ≥6 (adjusted relative hazard of 1.86, 2.38 and 2.71, respectively). Limitations: Classification of comorbidities for each patient was determined by clinical impression. Conclusions: The CCI and ESRD-CI have a limited ability to discriminate mortality risk for incident dialysis patients. Acknowledging the frequency with which they are used, this study emphasizes the need to re-examine the usefulness of previously derived comorbidity indices in contemporary dialysis cohorts