Institute for Cardiovascular Research Medical Center aR

Amsterdam, Netherlands

Institute for Cardiovascular Research Medical Center aR

Amsterdam, Netherlands

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PubMed | University Utrecht, Center Hospitalier Of Luniversite Of Montreal, Medical Center Alkmaar, Maasstad Hospital and Institute for Cardiovascular Research Medical Center aR
Type: Comparative Study | Journal: PloS one | Year: 2015

Hemodialysis (HD) patients have a high risk of infections. The uremic milieu has a negative impact on several immune responses. Online hemodiafiltration (HDF) may reduce the risk of infections by ameliorating the uremic milieu through enhanced clearance of middle molecules. Since there are few data on infectious outcomes in HDF, we compared the effects of HDF with low-flux HD on the incidence and type of infections.We used data of the 714 HD patients (age 64 14, 62% men, 25% Diabetes Mellitus, 7% catheters) participating in the CONvective TRAnsport STudy (CONTRAST), a randomized controlled trial evaluating the effect of HDF as compared to low-flux HD. The events were adjudicated by an independent event committee. The risk of infectious events was compared with Cox regression for repeated events and Cox proportional hazard models. The distributions of types of infection were compared between the groups.Thirty one percent of the patients suffered from one or more infections leading to hospitalization during the study (median follow-up 1.96 years). The risk for infections during the entire follow-up did not differ significantly between treatment arms (HDF 198 and HD 169 infections in 800 and 798 person-years respectively, hazard ratio HDF vs. HD 1.09 (0.88-1.34), P = 0.42. No difference was found in the occurrence of the first infectious event (either fatal, non-fatal or type specific). Of all infections, respiratory infections (25% in HDF, 28% in HD) were most common, followed by skin/musculoskeletal infections (21% in HDF, 13% in HD).HDF as compared to HD did not result in a reduced risk of infections, larger studies are needed to confirm our findings.ClinicalTrials.gov NCT00205556.


Mazairac A.H.A.,University Utrecht | de Wit G.A.,University Utrecht | Penne E.L.,University Utrecht | van der Weerd N.C.,University Utrecht | And 8 more authors.
Journal of Renal Nutrition | Year: 2011

Objective: Health-related quality of life (HRQOL) is an important outcome in dialysis care. Previous research has related protein-energy nutritional status to generic HRQOL domains, but it is still not clear as to how it relates to HRQOL domains that are unique to hemodialysis patients. Therefore, our aim was to study the relation between protein-energy nutritional status and kidney disease-specific HRQOL domains in hemodialysis patients. Design: This was a cross-sectional study. Setting: This study was performed at multiple centers. Patients or Other Participants: We evaluated the first 590 hemodialysis patients who had enrolled in the Convective Transport Study. Determinants: We measured protein-energy nutritional status by using the Subjective Global Assessment, albumin, normalized nitrogen appearance, creatinine, body mass index, and cholesterol. Main Outcome Measure: HRQOL was assessed by using the Kidney Disease Quality Of Life-Short Form. Results: In all, 83% of the cohort was found to be well-nourished on the basis of the Subjective Global Assessment. Multiple nutritional parameters were positively related to the physical summary of generic HRQOL and to the following kidney disease-specific HRQOL scales: the effects of the kidney disease on daily life, the burden of the kidney disease, and overall health. Conclusions: This study showed that, even in predominantly well-nourished hemodialysis patients, protein-energy nutritional status was significantly related to kidney disease-specific HRQOL. © 2011 National Kidney Foundation, Inc.


PubMed | University Utrecht, Center Hospitalier Of Luniversite Of Montreal, Institute for Cardiovascular Research Medical Center aR and Maasstad Hospital
Type: Journal Article | Journal: PloS one | Year: 2014

Resistance to erythropoiesis stimulating agents (ESA) is common in patients undergoing chronic hemodialysis (HD) treatment. ESA responsiveness might be improved by enhanced clearance of uremic toxins of middle molecular weight, as can be obtained by hemodiafiltration (HDF). In this analysis of the randomized controlled CONvective TRAnsport STudy (CONTRAST; NCT00205556), the effect of online HDF on ESA resistance and iron parameters was studied. This was a pre-specified secondary endpoint of the main trial. A 12 months analysis of 714 patients randomized to either treatment with online post-dilution HDF or continuation of low-flux HD was performed. Both groups were treated with ultrapure dialysis fluids. ESA resistance, measured every three months, was expressed as the ESA index (weight adjusted weekly ESA dose in daily defined doses [DDD]/hematocrit). The mean ESA index during 12 months was not different between patients treated with HDF or HD (mean difference HDF versus HD over time 0.029 DDD/kg/Hct/week [-0.024 to 0.081]; P=0.29). Mean transferrin saturation ratio and ferritin levels during the study tended to be lower in patients treated with HDF (-2.52% [-4.72 to -0.31]; P=0.02 and -49 ng/mL [-103 to 4]; P=0.06 respectively), although there was a trend for those patients to receive slightly more iron supplementation (7.1 mg/week [-0.4 to 14.5]; P=0.06). In conclusion, compared to low-flux HD with ultrapure dialysis fluid, treatment with online HDF did not result in a decrease in ESA resistance.ClinicalTrials.gov NCT00205556.


Den Hoedt C.H.,Maasstad Hospital | Den Hoedt C.H.,University Utrecht | Bots M.L.,University Utrecht | Grooteman M.P.C.,Institute for Cardiovascular Research Medical Center aR | And 6 more authors.
Kidney International | Year: 2014

Online hemodiafiltration may diminish inflammatory activity through amelioration of the uremic milieu. However, impurities in water quality might provoke inflammatory responses. We therefore compared the long-term effect of low-flux hemodialysis to hemodiafiltration on the systemic inflammatory activity in a randomized controlled trial. High-sensitivity C-reactive protein and interleukin-6 were measured for up to 3 years in 405 patients of the CONvective TRAnsport STudy, and albumin was measured at baseline and every 3 months in 714 patients during the entire follow-up. Differences in the rate of change over time of C-reactive protein, interleukin-6, and albumin were compared between the two treatment arms. C-reactive protein and interleukin-6 concentrations increased in patients treated with hemodialysis, and remained stable in patients treated with hemodiafiltration. There was a statistically significant difference in rate of change between the groups after adjustments for baseline variables (C-reactive protein difference 20%/year and interleukin-6 difference 16%/year). The difference was more pronounced in anuric patients. Serum albumin decreased significantly in both treatment arms, with no difference between the groups. Thus, long-term hemodiafiltration with ultrapure dialysate seems to reduce inflammatory activity over time compared to hemodialysis, but does not affect the rate of change in albumin. © 2014 International Society of Nephrology.


den Hoedt C.H.,Maasstad Hospital | Bots M.L.,Julius Center for Health science and Primary Care | Grooteman M.P.C.,Institute for Cardiovascular Research Medical Center aR | Mazairac A.H.A.,UMC Utrecht | And 5 more authors.
PLoS ONE | Year: 2013

Background:We studied the distribution of causes of death in the CONTRAST cohort and compared the proportion of cardiovascular deaths with other populations to answer the question whether cardiovascular mortality is still the principal cause of death in end stage renal disease. In addition, we compared patients who died from the three most common death causes. Finally, we aimed to study factors related to dialysis withdrawal.Methods:We used data from CONTRAST, a randomized controlled trial in 714 chronic hemodialysis patients comparing the effects of online hemodiafiltration versus low-flux hemodialysis. Causes of death were adjudicated. The distribution of causes of death was compared to that of the Dutch dialysis registry and of the Dutch general population.Results:In CONTRAST, 231 patients died on treatment. 32% died from cardiovascular disease, 22% due to infection and 23% because of dialysis withdrawal. These proportions were similar to those in the Dutch dialysis registry and the proportional cardiovascular mortality was similar to that of the Dutch general population. cardiovascular death was more common in patients <60 years. Patients who withdrew were older, had more co-morbidity and a lower mental quality of life at baseline. Patients who withdrew had much co-morbidity. 46% died within 5 days after the last dialysis session.Conclusions:Although the absolute risk of death is much higher, the proportion of cardiovascular deaths in a prevalent end stage renal disease population is similar to that of the general population. In older hemodialysis patients cardiovascular and non-cardiovascular death risk are equally important. Particularly the registration of dialysis withdrawal deserves attention. These findings may be partly limited to the Dutch population. © 2013 den Hoedt et al.


Mostovaya I.M.,University Utrecht | Blankestijn P.J.,University Utrecht | Bots M.L.,University Utrecht | Van Den Dorpel M.A.,Maasstad Hospital | And 4 more authors.
Blood Purification | Year: 2014

Background/Aims: Sub-analyses of three large trials showed that hemodiafiltration (HDF) patients who achieved the highest convection volumes had the lowest mortality risk. The aims of this study were (1) to identify determinants of convection volume and (2) to assess whether differences exist between patients achieving high and low volumes. Methods: HDF patients from the CONvective TRAnsport STudy (CONTRAST) with a complete dataset at 6 months (314 out of a total of 358) were included in this post hoc analysis. Determinants of convection volume were identified by regression analysis. Results: Treatment time, blood flow rate, dialysis vintage, serum albumin and hematocrit were independently related. Neither vascular access nor dialyzer characteristics showed any relation with convection volume. Except for some variation in body size, patient characteristics did not differ across tertiles of convection volume. Conclusion: Treatment time and blood flow rate are major determinants of convection volume. Hence, its magnitude depends on center policy rather than individualized patient prescription. © 2014 S. Karger AG, Basel.


Mazairac A.H.A.,University Utrecht | de Wit G.A.,University Utrecht | de Wit G.A.,National Institute of Public Health and the Environment | Grooteman M.P.C.,Institute for Cardiovascular Research Medical Center aR | And 10 more authors.
Clinical Journal of the American Society of Nephrology | Year: 2013

Background and objectives It is unclear if hemodiafiltration leads to a better quality of life compared with hemodialysis. It was, therefore, the aim of this study to assess the effect of hemodiafiltration on quality of life compared with hemodialysis in patients with ESRD. Design, setting, participants, & measurements This study analyzed the data of 714 patients with a median follow- up of 2 years from the Convective Transport Study. The patients were enrolled between June of 2004 and December of 2009. The Convective Transport Study is a randomized controlled trial on the effect of online hemodiafiltration versus low-flux hemodialysis on all-cause mortality. Quality of life was assessed with the Kidney Disease Quality of Life-Short Form. This questionnaire provides data for a physical and mental composite score and describes kidney disease-specific quality of life in 12 domains. The domains have scales from 0 to 100. Results There were no significant differences in changes in health-related quality of life over time between patients treated with hemodialysis (n=358) or hemodiafiltration (n=356). The quality of life domain patient satisfaction declined over time in both dialysis modalities (hemodialysis: -2.5/yr, -3.4 to -1.5, P<0.001; hemodiafiltration: -1.4/yr, -2.4 to -0.5, P=0.004). Conclusions Compared with hemodialysis, hemodiafiltration had no significant effect on quality of life over time. © 2013 by the American Society of Nephrology.


Van Der Weerd N.C.,University Utrecht | Grooteman M.P.C.,Institute for Cardiovascular Research Medical Center aR | Bots M.L.,University Utrecht | Van Den Dorpel M.A.,Maasstad Hospital | And 10 more authors.
Nephrology Dialysis Transplantation | Year: 2013

Background. The development of atherosclerosis may be enhanced by iron accumulation in macrophages. Hepcidin-25 is a key regulator of iron homeostasis, which downregulates the cellular iron exporter ferroportin. In haemodialysis (HD) patients, hepcidin-25 levels are increased. Therefore, it is conceivable that hepcidin-25 is associated with all-cause mortality and/or fatal and non-fatal cardiovascular (CV) events in this patient group. The aim of the current analysis was to study the relationship between hepcidin-25 and all-cause mortality and both fatal and non-fatal CV events in chronic HD patients. Methods. Data from 405 chronic HD patients included in the CONvective TRAnsport STudy (NCT00205556) were studied (62% men, age 63.7 ± 13.9 years [mean ± SD]). The median (range) follow-up was 3.0 (0.8-6.6) years. Hepcidin-25 was measured with mass spectrometry. The relationship between hepcidin-25 and all-cause mortality or fatal and non-fatal CV events was investigated with multivariate Cox proportional hazard models. Results. Median (interquartile range) hepcidin-25 level was 13.8 (6.6-22.5) nmol/L. During follow-up, 158 (39%) patients died from any cause and 131 (32%) had a CV event. Hepcidin-25 was associated with all-cause mortality in an unadjusted model [hazard ratio (HR) 1.14 per 10 nmol/L, 95% CI 1.03-1.26; P = 0.01], but not after adjustment for all confounders including high-sensitive C-reactive protein (HR 1.02 per 10 nmol/L, 95% CI 0.87-1.20; P = 0.80). At the same time, hepcidin-25 was significantly related to fatal and non-fatal CV events in a fully adjusted model (HR 1.24 per 10 nmol/L, 95% CI 1.05-1.46, P = 0.01). Conclusion. Hepcidin-25 was associated with fatal and nonfatal CV events, even after adjustment for inflammation. Furthermore, inflammation appears to be a significant confounder in the relation between hepcidin-25 and all-cause mortality. These findings suggest that hepcidin-25 might be a novel determinant of CV disease in chronic HD patients. © The Author 2013. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.


Den Hoedt C.H.,University Utrecht | Den Hoedt C.H.,Maasstad Hospital | Mazairac A.H.A.,University Utrecht | Van Den Dorpel M.A.,Maasstad Hospital | And 2 more authors.
Contributions to Nephrology | Year: 2011

Online hemodiafiltration may improve clinical outcome in end-stage kidney disease. The supposed mechanism is the improved clearance of uremic toxins by the convective transport which is added to the standard diffusive transport. This review summarizes the effects of hemodiafiltration on mortality, inflammation and health-related quality of life. Copyright © 2011 S. Karger AG, Basel.


van der Weerd N.C.,University of Amsterdam | Grooteman M.P.C.,Institute for Cardiovascular Research Medical Center aR | Bots M.L.,University Utrecht | van den Dorpel M.A.,Maasstad Hospital | And 10 more authors.
PLoS ONE | Year: 2012

Hepcidin-25, the bioactive form of hepcidin, is a key regulator of iron homeostasis as it induces internalization and degradation of ferroportin, a cellular iron exporter on enterocytes, macrophages and hepatocytes. Hepcidin levels are increased in chronic hemodialysis (HD) patients, but as of yet, limited information on factors associated with hepcidin-25 in these patients is available. In the current cross-sectional study, potential patient-, laboratory- and treatment-related determinants of serum hepcidin-20 and -25, were assessed in a large cohort of stable, prevalent HD patients. Baseline data from 405 patients (62% male; age 63.7±13.9 [mean SD]) enrolled in the CONvective TRAnsport STudy (CONTRAST; NCT00205556) were studied. Predialysis hepcidin concentrations were measured centrally with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Patient-, laboratory- and treatment related characteristics were entered in a backward multivariable linear regression model. Hepcidin-25 levels were independently and positively associated with ferritin (p<0.001), hsCRP (p<0.001) and the presence of diabetes (p = 0.02) and inversely with the estimated glomerular filtration rate (p = 0.01), absolute reticulocyte count (p = 0.02) and soluble transferrin receptor (p<0.001). Men had lower hepcidin-25 levels as compared to women (p = 0.03). Hepcidin-25 was not associated with the maintenance dose of erythropoiesis stimulating agents (ESA) or iron therapy. In conclusion, in the currently studied cohort of chronic HD patients, hepcidin-25 was a marker for iron stores and erythropoiesis and was associated with inflammation. Furthermore, hepcidin-25 levels were influenced by residual kidney function. Hepcidin-25 did not reflect ESA or iron dose in chronic stable HD patients on maintenance therapy. These results suggest that hepcidin is involved in the pathophysiological pathway of renal anemia and iron availability in these patients, but challenges its function as a clinical parameter for ESA resistance. © 2012 van der Weerd et al.

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