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BACKGROUND & AIMS: Despite modern treatment, risk for cardiovascular disease and mortality in patients with chronic kidney disease (CKD) is unacceptably high. Observational studies have shown associations of magnesium with risk for several clinical outcomes in CKD of variable magnitude. The aim of this review is to provide a systematic overview and meta-analysis of longitudinal studies assessing the association of plasma magnesium concentration with clinically relevant outcomes in adult patients with chronic kidney disease, with a minimal follow-up of 6 months. Primary outcomes of interest were all-cause mortality, cardiovascular mortality, cardiovascular events, sudden death and hospitalisation.METHODS: The electronic databases PubMed, Embase and The Cochrane Library were searched using terms relating to plasma magnesium and CKD patients, and two authors independently selected eligible studies. Study quality was assessed according to the Newcastle-Ottawa Scale. Results of studies with a comparable magnesium exposure and outcome measure, were pooled using a random-effects meta-regression analysis.RESULTS: The search yielded 6156 records of which 33 studies, involving 348,059 patients, met the eligibility criteria. Finally, 22 studies could be included in the meta-analysis. Higher magnesium was associated with a lower risk for all-cause mortality (HR 0.90 [0.87-0.94] per 0.1 mmol/L increase of magnesium) and cardiovascular mortality and events (HR 0.85 [0.77-0.94] per 0.1 mmol/L).CONCLUSIONS: Magnesium concentration is inversely associated with all-cause mortality and cardiovascular mortality and events. Therefore, increasing magnesium may improve risk in patients with chronic kidney disease. This meta-analysis forms a firm base for future prospective trials to test whether increasing plasma magnesium, indeed has beneficial effects on clinical outcomes.

A funnel plot is a graphical method to evaluate health‐care quality by comparing hospital performances on certain outcomes. So far, in nephrology, this method has been applied to clinical outcomes like mortality and complications. However, patient‐reported outcomes (PROs; eg, health‐related quality of life [HRQOL]) are becoming increasingly important and should be incorporated into this quality assessment. Using funnel plots has several advantages, including clearly visualized precision, detection of volume‐effects, discouragement of ranking hospitals and easy interpretation of results. However, without sufficient knowledge of underlying methods, it is easy to stumble into pitfalls, such as overinterpretation of standardized scores, incorrect direct comparisons of hospitals and assuming a hospital to be in‐control (ie, to perform as expected) based on underpowered comparisons. Furthermore, application of funnel plots to PROs is accompanied by additional challenges related to the multidimensional nature of PROs and difficulties with measuring PROs. Before using funnel plots for PROs, high and consistent response rates, adequate case mix correction and high‐quality PRO measures are required. In this article, we aim to provide insight into the use and interpretation of funnel plots by presenting an overview of the basic principles, pitfalls and considerations when applied to PROs, using examples from Dutch routine dialysis care., SUMMARY AT A GLANCE The statistical review provides insights into the use and interpretation of funnel plots by presenting an overview of the basic principles, pitfalls and considerations when applied to patient‐reported outcomes using examples from Dutch routine dialysis care.

Background Although the number of patients with end-stage kidney disease is growing, the number of patients who perform dialysis at home has decreased during the past two decades. The aim of this study was to explore time trends in the use of home dialysis in the Netherlands. Methods Dialysis episodes of patients who started dialysis treatment were studied using Dutch registry data (RENINE). The uptake of home dialysis between 1997 through 2016 was evaluated in time periods of 5 years. Home dialysis was defined as start with peritoneal dialysis or home haemodialysis, or transfer to either within 2 years of dialysis initiation. All analyses were stratified for age categories. Mixed model logistic regression analysis was used to adjust for clustering at patient level. Results A total of 33 340 dialysis episodes in 31 569 patients were evaluated. Mean age at dialysis initiation increased from 62.5 +/- 14.0 to 65.5 +/- 14.5 years in in-centre haemodialysis patients, whereas it increased from 51.9 +/- 15.1 to 62.5 +/- 14.6 years in home dialysis patients. In patients = 65 years, the incidence of home dialysis remained constant, whereas mortality decreased. Conclusions In patients

Background Dialysis withdrawal is a common cause of death in dialysis-dependent patients. This study aims to describe dialysis withdrawal practice in The Netherlands, focussing on time trends, risk factors and centre variation. Methods Data were retrieved from the Dutch registry of kidney replacement therapy patients. All patients who started maintenance dialysis and died in the period 2000–2019 were included. The main outcome was death after dialysis withdrawal; all other causes of death were used for comparison. Time trends were analysed as unadjusted data (proportion per year) and the year of death was included in a multivariable logistic model. Univariable and multivariable analyses were performed to identify factors associated with withdrawal. Centre variation was compared using funnel plots. Results A total of 34 692 patients started dialysis and 18 412 patients died while on dialysis. Dialysis withdrawal was an increasingly common cause of death, increasing from 18.3% in 2000–2004 to 26.8% in 2015–2019. Of all patients withdrawing, 26.1% discontinued treatment within their first year. In multivariable analysis, increasing age, female sex, haemodialysis as a treatment modality and year of death were independent factors associated with death after dialysis withdrawal. Centre variation was large (80.7 and 57.4% within 95% control limits of the funnel plots for 2000–2009 and 2010–2019, respectively), even after adjustment for confounding factors. Conclusions Treatment withdrawal has become the main cause of death among dialysis-dependent patients in The Netherlands, with large variations between centres. These findings emphasize the need for timely advance care planning and improving the shared decision-making process on choosing dialysis or conservative care.

Background High concentrations of both phosphate and fibroblast growth factor 23 (FGF23) observed in chronic kidney disease (CKD) are associated with an increased risk of cardiovascular morbidity and mortality. Pulse wave velocity (PWV) is a surrogate marker for cardiovascular events and all-cause mortality. It is not known whether a reduction of FGF23 or phosphate alters cardiovascular risk. Sevelamer has shown to have the ability to reduce both phosphate and FGF23 concentrations. Furthermore, reduction of PWV is reported with sevelamer use as well, but it is unclear if this is mediated by decline of phosphate or FGF23. We investigated if sevelamer induced a decline in PWV and if this was associated with a reduction in FGF23. Methods In all, 24 normophosphataemic CKD Stage 3 patients started treatment with a fixed dose of sevelamer-carbonate (Renvela®) 2.4 g twice daily, with their usual diet for 8 weeks in a single-arm study. PWV was measured and blood samples were obtained before, during and after washout of treatment with sevelamer. Vascular calcification was quantified using the Kauppila Index (KI). The primary outcome was the change of PWV from baseline to 8 weeks of treatment and the secondary endpoint was the difference of FGF23 following treatment with sevelamer. One of the linear mixed models was used to analyse the association between treatment and outcome. Mediation analysis was performed as a sensitivity analysis. The study was registered in the Dutch trial register (http://www.trialregister.nl: NTR2383). Results A total of 18 patients completed 8 weeks of treatment with sevelamer and were analysed. Overall, treatment with sevelamer did not induce a significant reduction of PWV (β = −0.36, P = 0.12). However, in patients with less vascular calcification (lower KI score), there was a statistically significant reduction of PWV, adjusted for mean arterial pressure, after treatment (β = 0.63, P = 0.02). Addition of FGF23 to the model did not alter this association. Mediation analysis yielded similar results. FGF23 did not decrease during treatment with sevelamer. Conclusion In this short-term pilot study in normophosphataemic CKD patients, treatment with sevelamer did not improve PWV. In subgroup analysis, however, PWV improved in patients with no or limited abdominal aorta calcifications. This was not associated with a decline of FGF23.

The correlation coefficient is a statistical measure often used in studies to show an association between variables or to look at the agreement between two methods. In this paper, we will discuss not only the basics of the correlation coefficient, such as its assumptions and how it is interpreted, but also important limitations when using the correlation coefficient, such as its assumption of a linear association and its sensitivity to the range of observations. We will also discuss why the coefficient is invalid when used to assess agreement of two methods aiming to measure a certain value, and discuss better alternatives, such as the intraclass coefficient and Bland–Altman’s limits of agreement. The concepts discussed in this paper are supported with examples from literature in the field of nephrology.

The aim of this study was to investigate 28-day mortality after COVID-19 diagnosis in the European kidney replacement therapy population. In addition, we determined the role of patient characteristics, treatment factors, and country on mortality risk using ERA-EDTA Registry data on patients receiving kidney replacement therapy in Europe between February 1, 2020 and April 30, 2020. Additional data on all patients with a diagnosis of COVID-19 were collected from seven European countries encompassing 4298 patients. COVID-19 attributable mortality was calculated using propensity-score matched historic controls and after 28 days of follow-up was 20.0% (95% confidence interval 18.7%-21.4%) in 3285 patients receiving dialysis, and 19.9% (17.5%-22.5%) in 1013 recipients of a transplant. We identified differences in COVID-19 mortality across countries, and an increased mortality risk in older patients receiving kidney replacement therapy and male patients receiving dialysis. In recipients of kidney transplants older than 75 years of age 44.3% (35.7%-53.9%) did not survive COVID-19. Mortality risk was 1.28 (1.02-1.60) times higher in transplant recipients compared with matched dialysis patients. Thus, the pandemic has had a substantial effect on mortality in patients receiving kidney replacement therapy; a highly vulnerable population due to underlying chronic kidney disease and high prevalence of multimorbidity., Graphical abstract

Rationale & Objective Dialysis patients judge health-related quality of life (HRQoL) as an essential outcome. Remarkably, little is known about HRQoL differences between home dialysis and in-center hemodialysis (HD) patients worldwide. Study Design Systematic review and meta-analysis. Setting & Study Populations Search strategies were performed on the Cochrane Library, Pubmed, and EMBASE databases between 2007 and 2019. Home dialysis was defined as both peritoneal dialysis and home HD. Selection Criteria for Studies Randomized controlled trials and observational studies that compared HRQoL in home dialysis patients versus in-center HD patients. Data Extraction The data extracted by 2 authors included HRQoL scores of different questionnaires, dialysis modality, and subcontinent. Analytical Approach Data were pooled using a random-effects model and results were expressed as standardized mean difference (SMD) with 95% CIs. Heterogeneity was explored using subgroup analyses. Results Forty-six articles reporting on 41 study populations were identified. Most studies were cross-sectional in design (90%), conducted on peritoneal dialysis patients (95%), and used the 12-item or 36-item Short-Form Health Survey questionnaires (83%). More than half the studies showed moderate or high risk of bias. Pooled analysis of 4,158 home dialysis patients and 7,854 in-center HD patients showed marginally better physical HRQoL scores in home dialysis patients compared with in-center HD patients (SMD, 0.14; 95% CI, 0.04 to 0.24), although heterogeneity was high (I2>80%). In a subgroup analysis, Western European home dialysis patients had higher physical HRQoL scores (SMD, 0.39; 95% CI, 0.17 to 0.61), while home dialysis patients from Latin America had lower physical scores (SMD, −0.20; 95% CI, −0.28 to −0.12). Mental HRQoL showed no difference in all analyses. Limitations No randomized controlled trials were found and high heterogeneity among studies existed. Conclusions Although pooled data showed marginally better physical HRQoL for home dialysis patients, the quality of design of the included studies was poor. Large prospective studies with adequate adjustments for confounders are necessary to establish whether home dialysis results in better HRQoL. Trial Registration PROSPERO 95985., Graphical abstract

Introduction: While concentric left ventricular hypertrophy (cLVH) predominates in non–dialysis-dependent chronic kidney disease (CKD), eccentric left ventricular hypertrophy (eLVH) is most prevalent in dialysis-dependent CKD stage 5 (CKD5D). In these patients, the risk of sudden death is 5× higher than in individuals with cLVH. Currently, it is unknown which factors determine left ventricular (LV) geometry and how it changes over time in CKD5D. Methods: Data from participants of the CONvective TRAnsport Study who underwent serial transthoracic echocardiography were used. Based on left ventricular mass (LVM) and relative wall thickness (RWT), 4 types of left ventricular geometry were distinguished: normal, concentric remodeling, eLVH, and cLVH. Determinants of eLVH were assessed with logistic regression. Left ventricular geometry of patients who died and survived were compared. Long-term changes in RWT and LVM were evaluated with a linear mixed model. Findings: Three hundred twenty-two patients (63.1 ± 13.3 years) were included. At baseline, LVH was present in 71% (cLVH: 27%; eLVH: 44%). Prior cardiovascular disease (CVD) was positively associated with eLVH and s-blocker use inversely. None of the putative volume parameters showed any relationship with eLVH. Although eLVH was most prevalent in non-survivors, the distribution of left ventricular geometry did not vary over time. Discussion: The finding that previous CVD was positively associated with eLVH may result from the permanent high cardiac output and the strong tendency for aortic valve calcification in this group of long-term hemodialysis patients, who suffer generally also from chronic anemia and various other metabolic derangements. No association was found between eLVH and parameters of fluid balance. The distribution of left ventricular geometry did not alter over time. The assumption that LV geometry worsens over time in susceptible individuals, who then suffer from a high risk of dying, may explain these findings.

Due to continuing migration there is more interest in the mental health status of immigrants. The aim of this study is to determine the prevalence of depressive/anxiety symptoms in immigrant and native dialysis patients, and to explore if patient characteristics can explain differences. The Beck depression inventory and the beck anxiety inventory were used. Differences between native and immigrant patients were explored using logistic regression models adjusted for patient characteristics. The prevalence of depressive symptoms was 35% for 245 native patients and 50% for 249 immigrant patients. The prevalence of anxiety symptoms was 35% for native patients and 50% for immigrant patients. In addition, the prevalence for co-morbid depressive and anxiety symptoms was 20% for native patients and 32% for immigrant patients. Crude ORs for depressive/anxiety symptoms for immigrant patients versus native patients were 1.8 (1.2–2.5) and 1.7 (1.2–2.5), respectively. After adjustment for patient characteristics ORs remained the same. Clinicians should be aware that immigrant dialysis patients are more prone to develop depressive and anxiety symptoms. Cultural factors might play a role and should therefore be assessed in future research.

Background: Vascular calcification is seen in most patients on dialysis and is strongly associated with cardiovascular mortality. Vascular calcification is promoted by phosphate, which generally reaches higher levels in hemodialysis than in peritoneal dialysis. However, whether vascular calcification develops less in peritoneal dialysis than in hemodialysis is currently unknown. Therefore, we compared coronary artery calcification (CAC), its progression, and calcification biomarkers between patients on hemodialysis and peritoneal dialysis. Methods: We measured CAC in 134 patients who had been treated exclusively with hemodialysis (n = 94) or peritoneal dialysis (n = 40) and were transplantation candidates. In 57 of them (34 on hemodialysis and 23 on peritoneal dialysis), we also measured CAC progression annually up to 3 years and the inactive species of desphospho-uncarboxylated matrix Gla protein (dp-ucMGP), fetuin-A, osteoprotegerin. We compared CAC cross-sectionally with Tobit regression. CAC progression was compared in 2 ways: with linear mixed models as the difference in square root transformed volume score per year (ΔCAC SQRV) and with Tobit mixed models. We adjusted for potential confounders. Results: In the cross-sectional cohort, CAC volume scores were 92 mm3 in hemodialysis and 492 mm3 in peritoneal dialysis (adjusted difference 436 mm3; 95% CI –47 to 919; p = 0.08). In the longitudinal cohort, peritoneal dialysis was associated with significantly more CAC progression defined as ΔCAC SQRV (adjusted difference 1.20; 95% CI 0.09 to 2.31; p = 0.03), but not with Tobit mixed models (adjusted difference in CAC score increase per year 106 mm3; 95% CI –140 to 352; p = 0.40). Peritoneal dialysis was associated with higher osteoprotegerin (adjusted p = 0.02) but not with dp-ucMGP or fetuin-A. Conclusions: Peritoneal dialysis is not associated with less CAC or CAC progression than hemodialysis, and perhaps with even more progression. This indicates that vascular calcification does not develop less in peritoneal dialysis than in hemodialysis.

Objectives: Several chronic inflammatory diseases are associated with cardiovascular disease, but the risk in ANCA-associated vasculitis is poorly quantified. The aim of the present study was to review the evidence for an increased cardiovascular risk, including ischaemic heart disease, cerebrovascular accidents and peripheral arterial disease, in patients with ANCA-associated vasculitis.Methods: A comprehensive systematic review was conducted in accordance with guidelines of preferred reporting items for systematic reviews and meta-analyses. The databases PubMed, Embase.com and the Cochrane Library (Wiley) were searched for original observational studies comparing vasculitis patients with at least one control group. Summary estimates were derived with a random-effects model and reported as relative risks.Results: One thousand three hundred and seventy-five studies were identified. Seven studies were included, comprising almost 14 000 ANCA-associated vasculitis patients vs general population controls in six studies and chronic kidney disease patients in one study. ANCA-associated vasculitis carried a relative risk of 1.65 (95% CI: 1.23, 2.22) for all cardiovascular events, 1.60 (95% CI: 1.39, 1.84) for ischaemic heart disease and 1.20 (95% CI: 0.98, 1.48) for cerebrovascular accidents. We did not find studies that addressed the risk for peripheral arterial disease separately. No heterogeneity was seen in the estimates.Conclusion: This meta-analysis of observational studies supports an increase in cardiovascular risk in patients with ANCA-associated vasculitis of ∼65%, similar to that found in other chronic inflammatory diseases. Hence, there is a clear need for active cardiovascular risk management in patients with ANCA-associated vasculitis.

Purpose: The purposes of this study were to assess the importance of perceived sodium reduction barriers among patients with chronic kidney disease (CKD) and identify associated sociodemographic, clinical, and psychosocial factors. Method: A total of 156 patients with CKD completed a questionnaire assessing sodium reduction barriers (18 self-formulated items), depressive symptoms (Beck Depression Inventory), perceived autonomy support (Modified Health Care Climate Questionnaire), and self-efficacy (Partners in Health Questionnaire). Factor analysis was used to identify barrier domains. Correlation coefficients were computed to examine relationships between barrier domains and patient characteristics. Results: Nine barrier domains were identified. Barriers perceived as important were as follows: high sodium content in products, lack of sodium feedback, lack of goal setting and discussing strategies for sodium reduction, and not experiencing CKD-related symptoms (mean scores > 3.0 on 5-point scales, ranging from 1 ‘no barrier’ to 5 ‘very important barrier’). Other barriers (knowledge, attitude, coping skills when eating out, and professional support) were rated as moderately important (rated around midpoint), and the barrier ‘intrinsic motivation’ was rated as somewhat important (mean score = 1.9). Sodium reduction barrier domains were not associated with gender and kidney function, but were associated with age, level of education, number of comorbidities, perceived autonomy support, depressive symptoms, and self-efficacy (range r = 0.17–0.35). Patients with lower self-efficacy and perceived autonomy support scores experienced most sodium reduction barriers. Conclusion: Patients with CKD experience multiple important sodium reduction barriers and could benefit from support strategies that target various sodium reduction barriers and strengthen beliefs regarding self-efficacy and autonomy support. Additionally, environmental interventions should be implemented to reduce sodium levels in processed foods.

Erzsébet Horváth-Puhó,1 Marit M Suttorp,2 Henrik Frederiksen,1,3 Tiny Hoekstra,2 Olaf M Dekkers,1,2 Lars Pedersen,1 Suzanne C Cannegieter,2 Friedo W Dekker,2 Henrik Toft Sørensen1 1Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 2Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands; 3Department of Haematology, Odense University Hospital, Odense, Denmark Introduction: Erythropoiesis-stimulating agent (ESA) treatment has been associated with an increased risk of venous thromboembolism (VTE) in patients with solid tumors and with an increased risk of cardiovascular events in patients with chronic kidney disease. The ESA-related risk in patients with hematological neoplasms remains unclear. We, therefore, aimed to assess the ESA-related risk of VTE, myocardial infarction (MI), and stroke in patients with multiple myeloma (MM) and myelodysplastic syndrome (MDS). Materials and methods: We conducted a population-based cohort study in Denmark, using medical databases to identify 2,114 MDS patients and 3,105MM patients diagnosed in 2004–2013. Incidence rates per 1,000 person-years and hazard ratios (HRs) with 95% confidence intervals (CIs) for VTE, MI, and stroke associated with ESA treatment were computed. HRs were calculated in time-dependent Cox regression and adjusted for age, sex, MDS prognosis group, comorbidities, and treatments. Results: Incidence rates per 1,000 person-years for VTE, MI, and stroke were 10.8, 8.2, and 16.0 in MDS patients, and 21.9, 10.2 and 9.9 in MM patients without ESA treatment, respectively. MDS patients with ESA treatment had a 1.6-fold increased risk of MI (HR 1.60 [95% CI 0.90–2.86]) and an almost twofold increased risk of stroke (HR 1.94 [95% CI 1.28–2.94]). Adjusted HR for VTE was 1.04 (95% CI 0.57–1.89) compared with MDS patients without ESAs. In MM patients with ESAs compared with patients without ESAs, HRs were 1.41 (95% CI 0.96–2.08) for VTE, 1.23 (95% CI 0.68–2.20) for MI, and 1.63 (95% CI 0.96–2.77) for stroke. Conclusion: ESA use was associated with stroke in MDS patients. Among MM patients, ESA treatment was associated with a higher risk of all cardiovascular events, although all CIs included equivalence. Keywords: cohort study, epidemiology, erythropoietin, multiple myeloma, myelodysplastic syndromes, myocardial infarction, stroke, pulmonary embolism, venous thrombosis

ObjectivesNocturnal haemodialysis (NHD), characterised by 8-hour sessions ≥3 times a week, is known to improve clinical parameters in the short term compared with conventional-schedule haemodialysis (HD), generally 3×3.5–4 hours a week. We studied long-term effects of NHD and used patients on conventional HD/haemodiafiltration (HDF) as controls.DesignFour-year prospective follow-up of patients who switched to NHD; we compared patients with patients on HD/HDF using propensity score matching.Setting28 Dutch dialysis centres.ParticipantsWe included 159 patients starting with NHD any time since 2004, aged 56.7±12.9 years, with median dialysis vintage 2.3 (0.9–5.1) years. We propensity-score matched 100 patients on NHD to 100 on HD/HDF.Primary and secondary outcome measuresControl of hypertension (predialysis blood pressure, number of antihypertensives), phosphate (phosphate, number of phosphate binders), nutritional status and inflammation (albumin, C reactive protein and postdialysis weight) and anaemia (erythropoiesis-stimulating agent (ESA) resistance).ResultsSwitching to NHD was associated with a non-significant reduction of antihypertensives compared with HD/HDF (OR ConclusionsAfter switching to NHD, the lower need for antihypertensives, phosphate binders and ESA persists for at least 4 years. These sustained improvements in NHD contrast significantly with the course of these parameters during continued treatment with conventional-schedule HD and HDF. NHD provides an optimal form of dialysis, also suitable for patients expected to have a long waiting time for transplantation or those convicted to indefinite dialysis.

Background Anemia-correction trials indicated higher mortality rates in chronic kidney disease patients assigned to higher hemoglobin targets. The safety of the high erythropoiesis-stimulating agent (ESA) doses that these patients received has therefore been questioned. However, no trial that directly compares treatment with different ESA doses has been published. We thus aimed to estimate the effect of high ESA dose on mortality in an observational cohort of dialysis patients. Methods The Netherlands Cooperative Study on the Adequacy of Dialysis is a Dutch cohort study of incident dialysis patients in which ESA dose, comorbidities, and laboratory parameters were collected every 6 months. Mortality in patients with a high ESA dose (above median 6000 units/week) was compared with that in patients with no or low ESA dose with Cox regression analyses. To handle time-dependent confounding, a sequential Cox approach was used conditional on baseline covariates, with inverse probability of censoring weights (IPCW) for dependent censoring. Analyses were repeated with a marginal structural model (MSM) with inverse probability of treatment weights and IPCW. Results Hazard ratio (HR) for high ESA dose was 1.20 (95%CI 0.83–1.73) with a sequential Cox and 1.54 (95%CI 1.08–2.18) with an MSM. Truncation of weights in the MSM did not affect estimates. To compare, conventional Cox analyses indicated a baseline adjusted HR of 1.66 (95%CI 1.20–2.31). Conclusion Patients treated with high ESA dose have a 1.2–1.5 increased risk of mortality. Our analyses support guidelines advising a conservative ESA dosing regimen, which carefully weighs the patients' benefits and risks. Copyright © 2015 John Wiley & Sons, Ltd.

In hemodialysis patients, lower plasma magnesium (Mg) concentrations are associated with a higher overall and cardiovascular mortality. The optimal concentration appears to be above the reference range for the healthy population. Plasma Mg is not routinely measured after hemodialysis. Aim of this study was to determine the effect of routine hemodialysis on plasma Mg. Plasma Mg was measured in duplicate before (Mgpre) and after (Mgpost) dialysis in 6 consecutive hemodialysis sessions of 34 patients using a fixed 0.50 mmol/L dialysate Mg concentration. Mean Mgpre was 0.88 mmol/L (±0.14) and mean Mgpost was statistically significantly lower: mean intra-dialytic decline 0.10 mmol/L (95%-CI 0.06–0.13). A 0.10 mmol/L higher Mgpre was associated with a 0.03 mmol/L higher Mgpost (95%-CI 0.024–0.037). At a Mgpre of 0.74 mmol/L, Mgpost equalled Mgpre. There was an intra-dialytic decline of plasma Mg at higher Mgpre values and an increase at lower Mgpre values. In conclusion, in the majority of the hemodialysis patients, Mgpre concentrations are in the reference range of the healthy population, which may be too low for hemodialysis patients. Routine hemodialysis with the widely used 0.50 mmol/L dialysate Mg concentration, further declines magnesium in the majority of patients. Current dialysate Mg concentrations may be too low.

Background Several chronic inflammatory diseases are associated with cardiovascular disease, but the cardiovascular risk in ANCA-associated vasculitis is poorly quantified. Objectives The aim of the present study is to review the evidence for the increased cardiovascular risk in patients with ANCA-associated vasculitis. Methods A comprehensive systematic review was conducted in accordance with guidelines of preferred reporting items for systematic reviews and meta-analyses (PRISMA). The databases PubMed, Embase.com and the Cochrane Library (Wiley) were searched for original observational studies reporting an estimate of the association between ANCA-associated vasculitis and cardiovascular events, including ischemic heart disease, cerebrovascular accidents and/or peripheral arterial disease. The quality of the included studies was assessed with the Newcastle–Ottawa Scale. Summary estimates were derived with a random-effects model and reported as relative risks. Results 1375 studies were identified and 7 studies were included comprising 14098 ANCA-associated vasculitis patients versus general population controls in 6 studies and chronic kidney disease patients in 1 study. ANCA-associated vasculitis carried a relative risk of 1.65 (95% confidence interval, 1.23–2.22) for all cardiovascular events, 1.60 (1.39–1.84) for ischemic heart disease and 1.20 (0.98–1.48) for cerebrovascular accidents. We did not find studies that addressed the risk for peripheral arterial disease separately. No heterogeneity was seen in the estimates. Conclusions This meta-analysis of observational studies supports an increase in cardiovascular risk of about 65% in patients with ANCA-associated vasculitis, similar to that found in other chronic inflammatory diseases. Hence, there is a clear need for active cardiovascular risk management in patients with ANCA-associated vasculitis. Disclosure of Interest None declared

Background: To evaluate the effectiveness and sustainability of self-managed sodium restriction in patients with chronic kidney disease.Study Design: Open randomized controlled trial.Setting & Participants: Patients with moderately decreased kidney function from 4 hospitals in the Netherlands.Intervention: Regular care was compared with regular care plus an intervention comprising education, motivational interviewing, coaching, and self-monitoring of blood pressure (BP) and sodium.Outcomes: Primary outcomes were sodium excretion and BP after the 3-month intervention and at 6-month follow-up. Secondary outcomes were protein excretion, kidney function, antihypertensive medication, self-efficacy, and health-related quality of life (HRQoL).Results: At baseline, mean sodium excretion rate was 163.6 +/- 64.9 (SD) mmol/24 h; mean estimated glomerular filtration rate was 49.7 +/- 25.6 mL/min/1.73 m(2); median protein excretion rate was 0.8 (IQR, 0.4-1.7) g/24 h; and mean 24-hour ambulatory systolic and diastolic BPs were 129 +/- 15 and 76 +/- 9 mm Hg, respectively. Compared to regular care only (n = 71), at 3 months, the intervention group (n = 67) showed reduced sodium excretion rate (mean change, -30.3 [95% CI, -54.7 to -5.9] mmol/24 h), daytime ambulatory diastolic BP (mean change, -3.4 [95% CI, -6.3 to -0.6] mm Hg), diastolic office BP (mean change, -5.2 [95% CI, -8.4 to -2.1] mm Hg), protein excretion (mean change, -0.4 [95% CI, -0.7 to -0.1] g/24h), and improved self-efficacy (mean change, 0.5 [95% CI, 0.1 to 0.9]). At 6 months, differences in sodium excretion rates and ambulatory BPs between the groups were not significant, but differences were detected in systolic and diastolic office BPs (mean changes of -7.3 [95% CI, -12.7 to -1.9] and -3.8 [95% CI, -6.9 to -0.6] mm Hg, respectively), protein excretion (mean changes, -0.3 [95% CI, -0.6 to -0.1] g/24h), and self-efficacy (mean change, 0.5 [95% CI, 0.0 to 0.9]). No differences in kidney function, medication, and HRQoL were observed.Limitations: Nonblinding, relatively low response rate, and missing data.Conclusions: Compared to regular care only, this self-management intervention modestly improved outcomes, although effects on sodium excretion and ambulatory BP diminish over time. (C) 2016 by the National Kidney Foundation, Inc.

BACKGROUND Infections are a major cause of morbidity and mortality among dialysis patients. Dialysis modality has been hypothesized to be a potential immunomodulatory factor. The objective of this study was to determine the influence of the first dialysis modality on the risk for infections on dialysis. METHODS Our study was conducted utilizing the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD) cohort of incident dialysis patients. Medical records of all patients from two tertiary care university hospitals and three regional hospitals were reviewed using pre-specified criteria. Information about infections was collected from the start of dialysis until death, modality switch, study withdrawal, kidney transplantation or at the end of the study. Age-standardized incidence rates for infections were calculated. Poisson regression analysis was used to calculate adjusted incidence rate ratios (IRRs). RESULTS In total, 452 patients, of whom 285 started with haemodialysis (HD) and 167 with peritoneal dialysis (PD), were included. The median follow-up time on the first dialysis modality was similar for HD and PD, 1.8 and 2.0 dialysis years, respectively. During the first 6 months, the age-standardized infection incidence rate was higher on HD compared with PD patients (P = 0.02). Overall, PD patients had a higher infection risk [adjusted IRR: 1.65, 95% confidence interval (CI): 1.34-2.03], which could be attributed to a 4-fold increased risk for dialysis technique-related infections. The risk for non-dialysis technique-related infections was lower in PD patients (adjusted IRR: 0.56, 95% CI: 0.40-0.79). CONCLUSIONS Overall, PD patients carry a higher risk for infections. Interestingly, the risk for non-dialysis technique-related infections was higher in HD patients. The links between dialysis modality and the immune system are expected to explain this difference, but future studies are needed to test these assumptions.

The effect of diuretics on residual renal function expressed as residual GFR (rGFR) and urine volume (rUV) using 24-hour urine collections has not been well examined in hemodialysis (HD) patients. We present a small (seven patient) but provocative case series describing a strikingly low rate of decline in rUV and rGFR (average of creatinine and urea clearances, 24-hour urine collections) in patients treated with increasing doses of furosemide (up to 360 mg/day) during the first 2 years after initiation of HD. Between 6 and 12 months, the mean rUV fell by 1 ml/month, whereas rGFR declined by 0.03 ml/min/1.73 m(2) /month. The mean rate of decline from 12 to 24 months for rUV (33 ml/month) and rGFR (0.02 ml/min/1.73 m(2) /month) were also low. While data are clearly limited and the observation retrospective, they are consistent with the better documented benefit of diuretics observed in end-stage renal disease patients treated with peritoneal dialysis.

BackgroundThe guidelines for anaemia management in chronic kidney disease (CKD) patients have changed substantially during the past 10 years. We here evaluate whether these changes are followed by subsequent modifications in physicians' anaemia management in Sweden. MethodsWe included patients incident to the Swedish Renal Registry for CKD non-dialysis (CKD-ND, referred patients with an estimated glomerular filtration rate 120 g/L decreased, especially between 2008-09 and 2010-11. Iron use increased over time, mainly in the HD population, but also among CKD-ND ESA non-users. ConclusionsChanges in guidelines have influenced the clinical anaemia practice of Swedish nephrology care, resulting in lower ESA use and lower Hb levels.

BackgroundHeight is a strong prognostic factor in cystic fibrosis (CF) and is usually compared to reference values of healthy children by expressing height as a z-score height-for-age (HFA). However, HFA does not take into account a potential delay in bone age (BA) and the genetic potential of the child and could therefore result in misclassification of short stature.MethodsIn 169 children with CF height, BA and target height (TH) were assessed. HFA, height for bone age (HBA), HFA adjusted for target height (HFA/TH) and HBA adjusted for target height (HFA/TH) were determined and children were categorized according to these four methods.ResultsMean z-scores of the four methods ranged from −0.1±0.8 (HBA/TH) to −0.5±1.0 (HFA). Prevalence of short stature (z-score

The aim of this study was to investigate correlates of fibrinogen concentration in black South Africans, as well as its association with cardiovascular disease (CVD) risk and whether urbanisation influences this association. A total of 1,006 rural and 1,004 urban black South Africans from the PURE study were cross-sectionally analysed. The association of fibrinogen with CVD risk was determined by investigating the association of fibrinogen with other CVD risk markers as well as with predicted CVD risk using the Reynolds Risk score. The rural group had a significantly higher fibrinogen concentration than the urban group, despite higher levels of risk factors and increased predicted CVD risk in the urban group. Increased levels of CVD risk factors were, however, still associated with increased fibrinogen concentration. Fibrinogen correlated significantly, but weakly, with overall predicted CVD risk. This correlation was stronger in the urban than in the rural group. Multiple regression analysis showed that a smaller percentage of the variance in fibrinogen is explained by the traditional CVD risk factors in the rural than in the urban group. In conclusion, fibrinogen is weakly associated with CVD risk (predicted overall risk as well with individual risk factors) in black South Africans, and is related to the degree of urbanisation. Increased fibrinogen concentration, in black South Africans, especially in rural areas, is largely unexplained, and likely not strongly correlated with traditional CVD-related lifestyle and pathophysiological processes. This does, however, not exclude the possibility that once increased, the fibrinogen concentration contributes to future development of CVD. http://dx.doi.org/10.1160/TH11-03-0192 http://www.schattauer.de/en/magazine/subject-areas/journals-a-z/thrombosis-and-haemostasis/contents/archive/issue/1439.html

We investigated the association between alcohol consumption and plasminogen activator inhibitor-1 activity (PAI-1act) and fibrinogen concentration in a black South African population presenting with lower PAI-1act and higher fibrinogen than what is typically observed in white populations. We, furthermore, wanted to investigate the effect of urbanization, sex, central obesity, increased triglycerides, 4G/5G polymorphism (PAI-1 only) and BMI on the association of alcohol with PAI-1act and fibrinogen. Data from 2010 apparently healthy, randomly collected black South African volunteers from the Prospective Urban and Rural Epidemiological (PURE) study were cross-sectionally analyzed. Alcohol consumption was recorded using quantitative food frequency questionnaires and fasting blood samples were collected for biochemical analysis including PAI-1act and fibrinogen. Heavy alcohol consumption is associated with significantly increased PAI-1act, in the total population as well as in the women separately, and tended to be so in men. This alcohol-related PAI-1act increase was observed in volunteers with increased triglycerides and central obesity but not in volunteers with normal levels and waist circumference. Urbanization, the 4G/5G polymorphism and BMI did not affect the association of alcohol with PAI-1act. Moderate alcohol consumption is associated with decreased fibrinogen concentration. Sex and level of urbanization did not affect the association of alcohol with fibrinogen. Fibrinogen decreased in normal and overweight volunteers but not in obese and centrally obese volunteers following moderate alcohol consumption. Triglyceride levels and waist circumference influence alcohol-related PAI-1act increase potentially through modulating adipocyte and triglyceride-induced PAI-1 production. Obesity prevented alcohol-related fibrinogen decrease possibly by counteracting the anti-inflammatory effect of moderate alcohol consumption.

In Western countries, cardiovascular disease is the leading cause of death in women. Prevalence of risk factors and clinical presentation are different in men and women and it is important to take these differences into account in both prevention and treatment. A healthy diet can substantially reduce cardiovascular risk. This article summarises the evidence of the effects of dietary interventions in women and discuss gender differences where data are available. For a number of specific dietary factors, there is some evidence of gender-specific effects. However, overall risk estimates are not very different from the ones observed in men, and, at this stage, the evidence is insufficient to advocate gender-specific dietary guidelines. Thus a heart-healthy diet is the same for both men and women. However, dietary advice might be more effective in women because of their stronger beliefs in the values of healthy eating. More efforts are needed to further increase awareness of cardiovascular risk and the benefits of a healthy diet. Thus, dietary counselling should be an integral part of the cardiovascular risk management in women.

The association between black tea consumption and iron status was investigated in a sample of African adults participating in the cross-sectional THUSA (Transition and Health during Urbanization of South Africans) study in the North West Province, South Africa. Data were analysed from 1605 apparently healthy adults aged 15–65 years by demographic and FFQ, anthropometric measurements and biochemical analyses. The main outcome measures were Hb and serum ferritin concentrations. No associations were seen between black tea consumption and concentrations of serum ferritin (menP = 0·059; womenP = 0·49) or Hb (menP = 0·33; womenP = 0·49). Logistic regression showed that tea consumption did not significantly increase risk for iron deficiency (men: OR 1·36; 95 % CI 0·99, 1·87; women: OR 0·98; 95 % CI 0·84, 1·13) nor for iron deficiency anaemia (men: OR 1·28; 95 % CI 0·84, 1·96; women: OR 0·93; 95 % CI 0·78, 1·11). Prevalence of iron deficiency and iron deficiency anaemia was especially high in women: 21·6 and 14·6 %, respectively. However, the likelihood of iron deficiency and iron deficiency anaemia was not significantly explained by tea consumption in sub-populations which were assumed to be at risk for iron deficiency. Regression of serum ferritin levels on tea consumption in women ≤ 40 years, adults with a daily iron intake ≤ 5·80 mg and adults with ferritin levels ≤ 26·60 μg/l, respectively, showedPvalues in the range of 0·28–0·88. Our findings demonstrate that iron deficiency and iron deficiency anaemia is not significantly explained by black tea consumption in a black adult population in South Africa. Tea intake was also not shown to be related to iron status in several sub-populations at risk for iron deficiency.

Objective Among immigrant chronic dialysis patients, depressive and anxiety symptoms are common. We aimed to examine the association of acculturation, i.e. the adaptation of immigrants to a new cultural context, and depressive and anxiety symptoms in immigrant chronic dialysis patients. Methods The DIVERS study is a prospective cohort study in five urban dialysis centers in the Netherlands. The association of five aspects of acculturation ("Skills", "Social integration", "Traditions", "Values and norms" and "Loss") and the presence of depressive and anxiety symptoms was determined using linear regression analyses, both univariate and multivariate. Results A total of 249 immigrant chronic dialysis patients were included in the study. The overall prevalence of depressive and anxiety symptoms was 51% and 47%, respectively. "Skills" and "Loss" were significantly associated with the presence of depressive and anxiety symptoms, respectively ("Skills" β=0.34, CI: 0.11–0.58, and "Loss" β=0.19, CI: 0.01–0.37; "Skills" β=0.49, CI: 0.25–0.73, and "Loss" β=0.33, CI: 0.13–0.53). The associations were comparable after adjustment. No significant associations were found between the other subscales and depressive and anxiety symptoms. Conclusion This study demonstrates that less skills for living in the Dutch society and more feelings of loss are associated with the presence of both depressive and anxiety symptoms in immigrant chronic dialysis patients.

Residual kidney function contributes substantially to solute clearance in dialysis patients but cannot be assessed without urine collection. We used serum filtration markers to develop dialysis-specific equations to estimate urinary urea clearance without the need for urine collection. In our development cohort, we measured 24-hour urine clearances under close supervision in 44 patients and validated these equations in 826 patients from the Netherlands Cooperative Study on the Adequacy of Dialysis. For the development and validation cohorts, median urinary urea clearance was 2.6 and 2.4 ml/min, respectively. During the 24-hour visit in the development cohort, serum β-trace protein concentrations remained in steady state but concentrations of all other markers increased. In the validation cohort, bias (median measured minus estimated clearance) was low for all equations. Precision was significantly better for β-trace protein and β2-microglobulin equations and the accuracy was significantly greater for β-trace protein, β2-microglobulin, and cystatin C equations, compared with the urea plus creatinine equation. Area under the receiver operator characteristic curve for detecting measured urinary urea clearance by equation-estimated urinary urea clearance (both 2 ml/min or more) were 0.821, 0.850, and 0.796 for β-trace protein, β2-microglobulin, and cystatin C equations, respectively; significantly greater than the 0.663 for the urea plus creatinine equation. Thus, residual renal function can be estimated in dialysis patients without urine collections.

Reducing sodium intake can prevent cardiovascular complications and further decline of kidney function in patients with chronic kidney disease. However, the vast majority of patients fail to reach an adequate sodium intake, and little is known about why they do not succeed.This study aims to identify perceived barriers and support strategies for reducing sodium intake among both patients with chronic kidney disease and health-care professionals.A purposive sample of 25 patients and 23 health-care professionals from 4 Dutch medical centers attended 8 focus groups. Transcripts were analyzed thematically and afterwards organized according to the phases of behavior change of self-regulation theory.Multiple themes emerged across different phases of behavior change, including the patients' lack of practical knowledge and intrinsic motivation, the maladaptive illness perceptions and refusal skills, the lack of social support and feedback regarding disease progression and sodium intake, and the availability of low-sodium foods.The results indicate the need for the implementation of support strategies that target specific needs of patients across the whole process of changing and maintaining a low-sodium diet. Special attention should be paid to supporting patients to set sodium-related goals, strengthening intrinsic motivation, providing comprehensive and practical information (e.g., about hidden salt in products), increasing social support, stimulating the self-monitoring of sodium intake and disease progression, and building a supportive patient-professional relationship that encompasses shared decision making and coaching. Moreover, global programs should be implemented to reduce sodium levels in processed foods, introduce sodium-related product labels, and increase consumer awareness.

BACKGROUND Phosphorus control is generally considered to be better in peritoneal dialysis (PD) patients as compared with haemodialysis (HD) patients. Predialysis phosphorus concentrations are misleading as a measure of phosphorus exposure in HD, as these neglect significant dialysis-related fluctuations. METHODS Parameters of mineral metabolism, including parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF-23), were determined in 79 HD and 61 PD patients. In PD, phosphorus levels were determined mid-morning. In HD, time-averaged phosphorus concentrations were modelled from measurements before and after the mid-week dialysis session. Weekly renal, dialytic and total phosphorus clearances as well as total mass removal were calculated from urine and dialysate collections. RESULTS Time-averaged serum phosphorus concentrations in HD (3.5 ± 1.0 mg/dL) were significantly lower than the mid-morning concentrations in PD (5.0 ± 1.4 mg/dL, P < 0.0001). In contrast, predialysis phosphorus concentrations (4.6 ± 1.4 mg/dL) were not different from PD. PTH and FGF-23 levels were significantly higher in PD. Despite higher residual renal function, total phosphorus clearance was significantly lower in PD (P < 0.0001). Total phosphorus mass removal, conversely, was significantly higher in PD (P < 0.05). CONCLUSIONS Our data suggest that the time-averaged phosphorus concentrations in patients treated with PD are higher as compared with patients treated with HD. Despite a better preserved renal function, total phosphorus clearance is lower in patients treated with PD. Additional studies are needed to confirm these findings in a population with a different demographic profile and dietary background and to define clinical implications.

Inter-ethnic variation in fibrinogen levels is hypothesized to be the result of differences in genetic background. No information is available regarding the contribution of genetics to fibrinogen γ' in Africans. Only limited information is available regarding the interaction between genotypes and total and γ' fibrinogen concentration in determining fibrin clot properties. Our aim was to investigate the effect of polymorphisms in the fibrinogen and Factor XIII genes on total and γ' fibrinogen and clot properties (turbidimetry) in 2010 black Africans as well as to determine their interactions. Significant associations were observed between rs1049636 (FGG gene), with total fibrinogen levels and between rs2070011 (FGA promoter area) and fibrinogen γ' levels. Significant associations were observed between single nucleotide polymorphisms (SNPs) in the FGA (rs2070011), FGB (rs1800787) and FGG (rs1049636) genes and fibre size. Significant interactions were found between total and/or γ' fibrinogen levels and SNPs in the FGA (rs2070011), FGB (rs2227385, rs1800787, rs1800788, rs4220) and F13A1 genes (rs5985) in determining clot properties. The different SNPs influenced the relationships between total and γ' fibrinogen levels with clot properties in opposing directions. Genetic influences may be ethnic-specific and should not only focus on fibrinogen concentration, but also on functionality in determining its role in CVD.

Introduction Increased fibrinogen is associated with cardiovascular disease risk. It is, however, not known to what extend environmental and genetic factors and/or their interaction influence changes in total and ¿’ fibrinogen over time. We aimed to determine how variation within the fibrinogen gene as well as environmental factors influence the change in total and ¿’ fibrinogen over time, and also whether gene-environment interactions influence total and ¿’ fibrinogen on a cross-sectional and prospective level in Africans. Materials and methods This prospective study consisted of 2010 participants at baseline and 1288 participants at follow-up (5 years). Results The gene–environment interactions that were associated with fibrinogen concentration on a cross-sectional level were: FGA 2224 G>A (rs2070011) with age (p = 0.005), FGB Arg448Lys (rs4220) with HIV status (p A (rs1800791) with HbA1c (p = 0.01). The only factor that independently influenced the change in total fibrinogen levels over time, was baseline CRP (p T (rs2066865) was the only single nucleotide polymorphism that independently influenced the change in fibrinogen ¿’ levels over time (p = 0.02). Only the FGG 9340 T>C (rs1049636) with HbA1c interaction was found to predict change in total fibrinogen concentrations over time (p = 0.005). Conclusions Gene-environment interactions influenced fibrinogen levels cross-sectionally and also mediated changes in levels over time.

Background. Short-Form 36 (SF-36) is a self-report healthrelated quality-of-life (HRQOL) questionnaire, widely used in dialysis patients. It consists of physical and mental component scores (PCS/MCS), ranging from 0 to 100. To improve efficiency, the Short-Form 12 (SF-12) was developed to reproduce PCS and MCS. We assessed the ability of SF-12 versus SF-36 to detect change over time, and the association of SF-12 versus SF36 with short-term and long-term mortality in dialysis patients. Methods. Patients were selected from the Netherlands Cooperative Study on the Adequacy of Dialysis (N= 1379), a prospective follow-up study among incident dialysis patients (62.1% HD) who completed SF-36 measurements every 6 months. Changes in scores of SF-12 versus SF-36 were compared with intra-class correlation coefficients (ICCs). Subsequently, Bland–Altman plots were used to assess limits of agreement. Relationship with mortality was assessed with Cox models with and without a time-dependent variable, adjusted for age, sex, ethnicity, comorbidity and dialysis modality at baseline. Results. ICC for change in scores was 0.90 for MCS and 0.84 for PCS. Mean difference was �0.1 and 0.2, respectively, and limits of agreement were �8.3 to 8.4 for MCS change in scores and �8.8 to 9.2 for PCS. Adjusted hazard ratio’s for mortality per 5 units increment were 0.87 (95% CI: 0.84–0.91) for MCS12, 0.87 (95% CI: 0.84–0.90) for MCS36, 0.79 (95% CI: 0.76–0.83) for PCS12 and 0.75 (95% CI: 0.71–0.78) for PCS36. Conclusions. SF-12 can be used to detect change in HRQOL in cohort studies on dialysis patients. SF-12 and SF-36 were similarly associated with short-term and long-term mortality. However, the wide limits of agreement indicate that SF-12 and SF-36 can give different scores on the individual level, suggesting that for individual purposes SF-36 instead of SF-12 should be used.

Background Erythropoietin (Epo) has been shown to improve myocardial function in models of experimental myocardial infarction, but has also been associated with a rise in thromboembolic events. Thus, the aim of this study was to investigate the influence of Epo on platelet activation and coagulation in patients with acute myocardial infarction (AMI). Methods The study was designed as a substudy of the randomised, double-blind, placebo controlled REVIVAL-3 (REgeneration of VItal Myocardium in ST-Segment EleVation MyocardiAL Infarction by Erythropoietin) study that investigated the effects of recombinant human Epo in AMI. Serial venous blood samples were collected before and after study medication. Circulating prothrombin fragment F1 + 2, FVII, active FVII, beta thromboglobulin (TG) and P-Selectin were measured before and 60 hours after randomization by immunoassay (n = 94). In a randomly selected subgroup platelet aggregation was measured using whole blood aggregometry (Multiplate Analyzer, n = 45). Results After 5 days an increase in FVII was observed after Epo as compared to placebo (P = 0.02), yet active FVII and prothrombin fragment F1 + 2 remained unchanged. Moreover, no statistically significant differences in circulating TG or P-selectin were observed between the groups. As an expected response to peri-interventional therapy with clopidogrel and aspirin, platelet aggregation after stimulation with ADP, TRAP, ASPI or collagen decreased 12 hours and 2 days after PCI. However, no difference between the Epo and the placebo group was observed. Conclusion After treatment with Epo in patients with AMI a slight increase in circulating FVII after Epo was not associated with an increase in active FVII, prothrombin fragment F1 + 2, TG or P-selectin. Moreover, platelet aggregation was not altered after treatment with Epo as compared to placebo. Trial registration ClinicalTrials.gov Identifier: NCT01761435

Background Erythropoiesis-stimulating agents (ESA) have been associated with a higher cardiovascular event and mortality rate in dialysis patients. The ESA-associated risk of arterial thrombotic events is mainly based on composite endpoints of anemia-correction trials targeting high hemoglobin levels. The ESA-associated risk of venous thromboembolism (VTE) has not been studied in dialysis patients yet. We therefore aimed to determine the association between ESA use and dose with ischemic stroke, myocardial infarction (MI) and VTE. Materials and Methods In NECOSAD, a Dutch cohort study of incident dialysis patients, data on ESA use and dose, comorbidities and laboratory parameters were routinely collected every 6 months. Thrombotic events were collected by chart review of all dialysis patients from 6 participating centers. Time-dependent Cox regression analysis was performed to calculate hazard ratios (HR) with 95% confidence interval (CI) for ischemic stroke, MI and VTE with updated information on ESA use and dose. Results Patients with ESA had a 2 times lower ischemic stroke rate than patients without ESA: adjusted HR 0.45 (95% CI 0.23-0.90), and an adjusted HR of 1.12 (95% CI 0.58-2.14) for MI. No evident ESA dose response effect was present. Unadjusted HR for VTE was 0.41 (95% CI 0.11-1.50) for patients with ESA compared to patients without, but the low event rate made further adjustments impossible. Conclusions In our observational cohort of dialysis patients, reflecting everyday clinical practice, ESA was not associated with an excess of thrombotic events. Further investigation is needed to enlighten the true cause of ESA-associated cardiovascular events and mortality.

Introduction: Erythropoiesis-Stimulating Agents (ESA) are hypothesized to increase cardiovascular mortality in patients with chronic kidney disease. One of the proposed mechanisms is the elevation of blood pressure (BP) by ESA. Therefore, we aimed to determine whether the use of ESA was associated with antihypertensive treatment and higher BP.Materials and Methods: In this cohort 502 incident pre-dialysis patients were included who started specialized pre-dialysis care in 25 clinics in the Netherlands. Data on medication including ESA use and dose, co-morbidities and BP were routinely collected every 6 months. Antihypertensive treatment and BP were compared for patients with and without ESA at baseline. Differences in antihypertensive medication and BP during pre-dialysis care were estimated with linear mixed models adjusted for age, sex, body mass index, cardiovascular disease, diabetes mellitus and estimated glomerular filtration rate.Results: At baseline, 95.6% of patients with ESA were treated with antihypertensive medication and 73.1% of patients without ESA. No relevant difference in BP was found. During pre-dialysis care patients with ESA used 0.77 (95% CI 0.63; 0.91) more classes of antihypertensive drugs. The adjusted difference in systolic blood pressure (SBP) was -0.3 (95% CI -22.7;2.0) mmHg and in diastolic blood pressure (DBP) was -1.0 (95% CI -2.1; 0.3) mmHg for patients with ESA compared to patients without ESA. Adjusted SBP was 3.7 (95% CI -1.6; 9.0) mmHg higher in patients with a high ESA dose compared to patients with a low ESA dose.Conclusions: Our study confirms the hypertensive effect of ESA, since ESA treated patients received more antihypertensive agents. However, no relevant difference in BP was found between patients with and without ESA, thus the increase in BP seems to be controlled for by antihypertensive medication.

Background: There are no available epidemiologic studies about the impact of ethnicity on outcomes of patients treated with peritoneal dialysis (PD) in South America. This study aims to assess the effect of ethnicity on the mortality of incident PD patients in Brazil. Study Design: Prospective observational cohort study of incident patients treated with PD. Settings & Participants: Patients 18 years or older who started PD therapy between December 2004 and October 2007 in 114 Brazilian dialysis centers. Predictors: Self-reported ethnicity defined by the Brazilian Institute of Geography and Statistics as black and brown versus white patients and baseline demographic, socioeconomic, clinical, and laboratory data were collected at baseline. Outcome: Mortality, using cumulative mortality curves in which kidney transplantation and transfer to hemodialysis therapy were treated as competing end points. Multivariate Cox proportional hazards analysis was used to adjust for gradually more potential explanatory variables, censored for kidney transplantation and transfer to hemodialysis therapy. Analyses were performed for all patients, as well as stratified for elderly (aged 65 years) and nonelderly patients. Results: 1,370 patients were white, 516 were brown, and 273 were black. The competing-risk model showed higher mortality in white patients compared with black and brown patients. With white patients as the reference, Cox proportional hazards analysis showed a crude HR for mortality of 0.77 (95% CI, 0.56-1.05) for black and 0.74 (95% CI, 0.59-0.94) for brown patients. After adjusting for potential explanatory factors, HRs were 0.67 (95% CI, 0.48-0.95) and 0.77 (95% CI, 0.43-1.01), respectively. The same results were observed in elderly and nonelderly patients. Limitations: Ethnicity was self-determined and some misclassification might have occurred. Conclusions: Black and brown Brazilian incident PD patients have a lower mortality risk compared with white patients. Am J Kidney Dis. 62(1):89-96. © 2013 by the National Kidney Foundation, Inc.

Data on genetic and environmental factors influencing PAI-1 levels and their consequent effect on clot lysis in black African populations are limited. We identified polymorphisms in the promoter area of the PAI-1 gene and determined their influence on PAI-1act levels and plasma clot lysis time (CLT). We also describe gene-environment interactions and the effect of urbanisation. Data from 2010 apparently healthy urban and rural black participants from the South African arm of the PURE study were cross-sectionally analysed. The 5G allele frequency of the 4G/5G polymorphism was 0.85. PAI-1act increased across genotypes in the urban subgroup (p = 0.009) but not significantly in the rural subgroup, while CLT did not differ across genotypes. Significant interaction terms were found between the 4G/5G polymorphism and BMI, waist circumference and triglycerides in determining PAI-1act, and between the 4G/5G polymorphism and fibrinogen and fibrinogen gamma prime in determining CLT. The C428T and G429A polymorphisms did not show direct relationships with PAI-1act or CLT but they did influence the association of other environmental factors with PAI-1act and CLT. Several of these interactions differed significantly between rural and urban subgroups, particularly in individuals harbouring the mutant alleles. In conclusion, although the 4G/5G polymorphism significantly affected PAI-1act, it contributed less than 1% to the PAI-1act variance. (Central) obesity was the biggest contributor to PAI-1act variance (12.5%). Urbanisation significantly influenced the effect of the 4G/5G polymorphism on PAI-1act as well as gene-environment interactions for the C428T and G429A genotypes in determining PAI-1act and CLT http://www.plosone.org/ http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0083151 DOI: 10.1371/journal.pone.0083151 SANPAD (South Africa - Netherlands Research Programme on Alternatives in Development); South African National Research Foundation (NRF GUN numbers 2069139, FA2006040700010 and FA2006041100003. South African Medical Research Council; the North-West University, Potchefstroom, South Africa; and the PHRI (Population Health Research Institute), ON, Canada

Background: In cystic fibrosis (CF), prophylactic supplementation of the fat-soluble vitamins A, D, E, and K is recommended. Limited data is available describing vitamin prescription adherence by adult patients. The aim of this study was to assess the use of prescribed vitamins and other nutritional supplements by adult CF patients. Methods: All adult CF patients (n = 111) registered at the Utrecht CF Center were invited to participate in a telephone survey on supplement use. Supplemental vitamin intakes were compared with recommendations. In a subsample, associations between supplemental intake and serum vitamin D and E values were assessed. Results: In this study 80 % of the patients reported the use of vitamin and/or mineral supplements. Fat-soluble vitamins were used by 43 % of pancreatic-sufficient (PS) and 81 % of pancreatic-insufficient (PI) patients. Of PI patients reporting supplemental vitamin use, only 9 % met the recommendations for vitamin A, 32 % for vitamin D, 59 % for vitamin E, and 81 % for vitamin K. Multivitamin supplements were used by 42 % of PI and by 29 % of PS patients. Other nutritional supplements were rarely used.Conclusion: A high percentage of PI patients use fat-soluble vitamins below recommendations. Therefore adequate monitoring of vitamin supplementation and status is warranted.

BACKGROUND: Bacterial contamination of blood products is a great hazard for development of fatal transfusion reactions. Bacterial screening of platelet concentrates (PC) by aerobic and anaerobic culturing (BacT/ALERT, bioMerieux) was introduced in the Netherlands in October 2001. STUDY DESIGN AND METHODS: In November 2002, a nationwide, uniform skin cleansing method was introduced with a double-swab disinfection with 70 percent isopropyl alcohol. One location routinely used an integrated diversion bag to collect the first 20 to 30 mL. RESULTS: Over the calendar years 2002 and 2003, in total 113,093 PCs derived from pooled buffy coats were screened. After introduction of the new disinfection method, 0.85 percent were initially positive. This was a small reduction compared to the previous disinfection methods under which 0.95 percent were initially positive. The location with use of the diversion bag showed a significantly lower frequency of bacterial contamination, with 0.50 percent before and 0.37 percent after introduction of 70 percent isopropyl alcohol. In addition 8000 apheresis PCs were also screened, showing 24 initially positive samples (0.30%). CONCLUSION: The use of the diversion bag and, to a lesser extent, the use of double swabs with 70 percent isopropyl alcohol, led to a reduction of contamination. As expected, predominant contamination with resident skin bacteria was reduced. The combination of diversion bag and new disinfection led to a frequency of initial positive results for pooled five-donor PCs, which is similar to that of single-donor apheresis PCs. Furthermore, the bacterial detection system and associated product recall procedures have been shown to be effective in preventing transfusion of contaminated PCs and/or related red cells, especially for rapidly growing bacteria.

Background Major depression is known to be related to higher cardiovascular mortality. However, epidemiological data regarding dispositional optimism in relation to mortality are scanty. Objective To test whether subjects who are optimistic live longer than those who are pessimistic. Design Our analysis formed part of a prospective population-based cohort study in the Netherlands (Arnhem Elderly Study). Setting General community. Participants Elderly subjects aged 65 to 85 years (999 men and women) completed the 30-item validated Dutch Scale of Subjective Well-being for Older Persons, with 5 subscales: health, self-respect, morale, optimism, and contacts. A total of 941 subjects (466 men and 475 women) had complete dispositional optimism data, and these subjects were divided into quartiles. Main Outcome Measure Number of deaths during the follow-up period. Results During the follow-up period of 9.1 years (1991-2001), there were 397 deaths. Compared with subjects with a high level of pessimism, those reporting a high level of optimism had an age- and sex-adjusted hazard ratio of 0.55 (95% confidence interval, 0.42-0.74; upper vs lower quartile) for all-cause mortality. For cardiovascular mortality, the hazard ratio was 0.23 (95% confidence interval, 0.10-0.55) when adjusted for age, sex, chronic disease, education, smoking, alcohol consumption, history of cardiovascular disease or hypertension, body mass index, and total cholesterol level. Protective trend relationships were observed between the level of optimism and all-cause and cardiovascular mortality ( P P = .001 for trend, respectively). Interaction with sex ( P = .04) supported a stronger protective effect of optimism in men than women for all-cause mortality but not for cardiovascular mortality. Conclusions Our results provide support for a graded and independent protective relationship between dispositional optimism and all-cause mortality in old age. Prevention of cardiovascular mortality accounted for much of the effect.