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

The association of functional status with mortality and dialysis modality change : results from the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS)

BACKGROUND: Little is known about the prevalence of functional impairment in peritoneal dialysis (PD) patients, its variation by country, and its association with mortality or transfer to hemodialysis. METHODS: A prospective cohort study was conducted in PD patients from 7 countries in the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS) (2014 - 2017). Functional status (FS) was assessed by combining self-reports of 8 instrumental and 5 basic activities of daily living, using the Lawton-Brody and the Katz questionnaires. Summary FS scores, ranging from 1.25 (most dependent) to 13 (independent), were based on the patient's ability to perform each activity with or without assistance. Logistic regression was used to estimate the odds ratio (OR; 95% confidence interval [CI]) of a FS score < 11 comparing each country with the United States (US). Cox regression was used to estimate the hazard ratio (HR; 95% CI) for the effect of a low FS score on mortality and transfer to hemodialysis, adjusting for case mix. RESULTS: Of 2,593 patients with complete data on FS, 48% were fully independent (FS = 13), 32% had a FS score 11 to < 13, 14% had a FS score 8 to < 11, and 6% had a FS score < 8. Relative to the US, low FS scores (< 11; more dependent) were more frequent in Thailand (OR = 10.48, 5.90 - 18.60) and the United Kingdom (UK) (OR = 3.29, 1.77 - 6.08), but similar in other PDOPPS countries. The FS score was inversely and monotonically associated with mortality but not with transfer to hemodialysis; the HR, comparing a FS score < 8 vs 13, was 4.01 (2.44 - 6.61) for mortality and 0.91 (0.58 - 1.43) for transfer to hemodialysis. CONCLUSION: Regional differences in FS scores observed across PDOPPS countries may have been partly due to differences in regional patient selection for PD. Functional impairment was associated with mortality but not with permanent transfer to hemodialysis

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

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

Approach to Hyponatremia in Congestive Heart Failure: A Survey of Canadian Specialist Physicians and Trainees

Background: Hyponatremia is a recognized complication of congestive heart failure (CHF) and is associated with reduced survival. Therefore, early identification and appropriate management of hyponatremia is important. The aim of this study was to determine the general approach amongst Canadian healthcare practitioners and trainees to the identification and management of hyponatremia complicating CHF. Methods: Respondents completed 15 multiple-choice style questions in 3 case scenarios regarding the approach to management of hyponatremia complicating CHF using an online survey on UKidney.com between November 2012 and May 2013. Results were presented as a proportion of averaged correct/incorrect responses amongst Canadian nephrologists, cardiologists, internists and trainees in each of two domains; pathophysiology and management. Management was further subdivided into correct and incorrect use of diuretic therapy, hypertonic saline, oral urea tablets, vasopressin receptor antagonists (vaptans) and rate of sodium correction. Correct responses were determined by an expert panel of Canadian nephrologists and cardiologists based on review of evidence informed guidelines and current recommendations. Results: There were 1757 responses to our online survey amongst 455 Canadian respondents, 1139 of which were from cardiologists, nephrologists, general internists, or trainees. Overall, the pathophysiology governing hyponatremia in CHF was correctly identified 68.7 % of the time ( n = 380 responses, averaged over 4 questions). Hyponatremia was managed inappropriately 43.6 % of the time, with trainees scoring best overall with correct responses 60.3 % of the time ( n = 759 responses, over 11 questions). Importantly, an incorrect rate for sodium correction was selected 61.1 % of the time overall, ( n = 211 responses, averaged over 3 questions). Conclusions: This study identified that there are differences in the understanding of pathophysiology and management strategies for hyponatremia in the context of CHF amongst Canadian specialist physicians and trainees. A more consistent approach to hyponatremia is required and might best be achieved through formal knowledge translation

Association Between First Post-operative Day Urine Output Following Kidney Transplantation and Short-Term and Long-Term Outcomes: A Retrospective Cohort Study

Background: The relationship between post-operative urine output (UO) following kidney transplantation and long-term graft function has not been well described. Objective: In this study, we examined the association between decreased UO on post-operative day 1 (POD1) and post-transplant outcomes. Design: This is a retrospective cohort study. Setting: Atlantic Canada. Patients: Patients from the 4 Atlantic Canadian provinces (Nova Scotia, New Brunswick, Newfoundland, and Prince Edward Island) who received a live or deceased donor kidney transplant from 2006 through 2019 through the multiorgan transplant program at the Queen Elizabeth II Health Sciences Centre (QEII) hospital in Halifax, Nova Scotia. Measurements: Using multivariable Cox proportional hazards models, we assessed the association of low POD1 UO (defined as ≤1000 mL) with death-censored graft loss (DCGL). In secondary analyses, we used adjusted logistic regression or Cox models as appropriate to assess the impact of UO on delayed graft function (DGF), prolonged length of stay (greater than the median for the entire cohort), and death. Results: Of the 991 patients included, 151 (15.2%) had a UO ≤1000 mL on POD1. Low UO was independently associated with DCGL (hazard ratio [HR] = 4.00, 95% confidence interval [CI] = 95% CI = 1.55-10.32), DGF (odds ratio [OR] = 45.25, 95% CI = 23.00-89.02), and prolonged length of stay (OR = 5.06, 95% CI = 2.95-8.69), but not death (HR = 0.81, 95% CI = 0.31-2.09). Limitations: This was a single-center, retrospective, observational study and therefore has inherent limitations of generalizability, data collection, and residual confounding. Conclusions: Overall, reduced post-operative UO following kidney transplantation is associated with an increased risk of DCGL, DGF, and prolonged hospital length of stay

Outcomes of major trauma among patients with chronic kidney disease and receiving dialysis in Nova Scotia: a retrospective analysis

Background The risk of death and complications after major trauma in patients with chronic kidney disease (CKD) is higher than in the general population, but whether this association holds true among Canadian trauma patients is unknown.Objectives To characterize patients with CKD/receiving dialysis within a regional major trauma cohort and compare their outcomes with patients without CKD.Methods All major traumas requiring hospitalization between 2006 and 2017 were identified from a provincial trauma registry in Nova Scotia, Canada. Trauma patients with stage ≥3 CKD (estimated glomerular filtration rate &lt;60 mL/min/1.73 m2) or receiving dialysis were identified by cross-referencing two regional databases for nephrology clinics and dialysis treatments. The primary outcome was in-hospital mortality; secondary outcomes included hospital/intensive care unit (ICU) length of stay (LOS) and ventilator-days. Cox regression was used to adjust for the effects of patient characteristics on in-hospital mortality.Results In total, 6237 trauma patients were identified, of whom 4997 lived within the regional nephrology catchment area. CKD/dialysis trauma patients (n=101; 28 on dialysis) were older than patients without CKD (n=4896), with higher rates of hypertension, diabetes, and cardiovascular disease, and had increased risk of in-hospital mortality (31% vs 11%, p&lt;0.001). No differences were observed in injury severity, ICU LOS, or ventilator-days. After adjustment for age, sex, and injury severity, the HR for in-hospital mortality was 1.90 (95% CI 1.33 to 2.70) for CKD/dialysis compared with patients without CKD.Conclusion Independent of injury severity, patients without CKD/dialysis have significantly increased risk of in-hospital mortality after major trauma

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