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BACKGROUND: Hyperphosphatemia is an independent risk factor for all-cause and cardiovascular mortality in hemodialysis (HD) patients. Phosphate control often is unsuccessful using conventional dialysis therapies. STUDY DESIGN: Short-term analysis of a secondary outcome of an ongoing randomized controlled trial. SETTING & PARTICIPANTS: 493 (84%) consecutive patients from 589 patients included in the Convective Transport Study (CONTRAST) by January 2009 from 26 centers in 3 countries. INTERVENTION: Online hemodiafiltration (HDF) versus continuation of low-flux HD. OUTCOMES: Differences in change from baseline to 6 months in phosphate levels and proportion of patients reaching phosphate treatment targets (phosphate < or = 5.5 mg/dL). MEASUREMENTS: Phosphate, use of phosphate-binding agents, and proportion of patients achieving treatment targets at baseline, 3 months, and 6 months. RESULTS: Phosphate levels decreased from 5.18 +/- 0.10 (SE) mg/dL at baseline to 4.87 +/- 0.10 mg/dL at 6 months in HDF patients (P < 0.001) and were stable in HD patients (5.10 +/- 0.10 mg/dL at baseline and 5.03 +/- 0.10 mg/dL after 6 months; P = 0.5). The difference in change in phosphate levels between HD and HDF patients (B = -0.24; 95% CI, -0.52 to 0.03; P = 0.08) increased after adjustment for phosphate-binder use (B = -0.36; 95% CI, -0.65 to -0.06; P = 0.02). The proportion of patients reaching phosphate treatment targets increased from 64% to 74% in HDF patients and was stable in HD patients (66% and 66%); the difference between groups reached statistical significance (P = 0.04). Nutritional parameters and residual renal function were similar in both treatment groups. LIMITATIONS: Only predialysis serum phosphate levels were measured; phosphate clearance could therefore not be calculated. CONCLUSION: HDF may help improve phosphate control. Whether this contributes to improved clinical outcome remains to be established. [ABSTRACT FROM AUTHOR]

Abstract Background The high incidence of cardiovascular disease in patients with end stage renal disease (ESRD) is related to the accumulation of uremic toxins in the middle and large-middle molecular weight range. As online hemodiafiltration (HDF) removes these molecules more effectively than standard hemodialysis (HD), it has been suggested that online HDF improves survival and cardiovascular outcome. Thus far, no conclusive data of HDF on target organ damage and cardiovascular morbidity and mortality are available. Therefore, the CONvective TRAnsport STudy (CONTRAST) has been initiated. Methods CONTRAST is a Dutch multi-center randomised controlled trial. In this trial, approximately 800 chronic hemodialysis patients will be randomised between online HDF and low-flux HD, and followed for three years. The primary endpoint is all cause mortality. The main secondary outcome variables are fatal and non-fatal cardiovascular events. Conclusion The study is designed to provide conclusive evidence whether online HDF leads to a lower mortality and less cardiovascular events as compared to standard HD.

Rationale & Objective: Research on shared decision making (SDM) in chronic kidney disease (CKD) has focused almost exclusively on the modality of kidney replacement treatment. We explored what other CKD decisions are recognized by patients, what their preferences and experiences are regarding these decisions, and how decisions are made during their interactions with medical care professionals., Study Design: Cross-sectional study., Setting & Participants: Patients with CKD receiving (outpatient) care in 1 of 2 Dutch hospitals., Exposure: Patients' preferred decisional roles for treatment decisions were measured using the Control Preferences Scale survey administered after a health care visit with medical professionals., Outcome: Number of decisions for which patients experienced a decisional role that did or did not match their preferred role. Observed levels of SDM and motivational interviewing in audio recordings of health care visits, measured using the 4-step SDM instrument (4SDM) and Motivational Interviewing Treatment Integrity coding tools., Analytical Approach: The results were characterized using descriptive statistics, including differences in scores between the patients' experienced and preferred decisional roles., Results: According to the survey (n=122) patients with CKD frequently reported decisions regarding planning (112 of 122), medication changes (82 of 122), or lifestyle changes (59 of 122). Of the 357 reported decisions in total, patients preferred that clinicians mostly (125 of 357) or fully (101 of 357) make the decisions. For 116 decisions, they preferred a shared decisional role. For 151 of 357 decisions, the patients' preferences did not match their experiences. Decisions were experienced as "less shared/patient-directed" (76 of 357) or "more shared/patient-directed" (75 of 357) than preferred. Observed SDM in 118 coded decisions was low (median4; range, 0 - 22). Motivational interviewing techniques were rarely used., Limitations: Potential recall and selection bias, and limited generalizability., Conclusions: We identified multiple discrepancies between preferred, experienced, and observed SDM in health care visits for CKD. Although patients varied in their preferred decisional role, a considerable number of patients expressed a preference for shared decision making for many decisions. However, SDM behavior during the health care visits was observed infrequently., Plain-Language Summary: Shared decision making (SDM) may be a valuable approach for common chronic kidney disease (CKD) decisions, but our knowledge is limited. We collected patient surveys after health care visits for CKD. Patients most frequently experienced decisions regarding planning, medication, and lifestyle. Three decisional roles were preferred by comparable numbers of patients: let the clinician alone decide, let the clinician decide for the most part, or "equally share" the decision. Patients' experiences of who made the decision did not always match their preferences. In audio recordings of the health care visits, we observed low levels of SDM behavior. These findings suggest that the preference for "sharing decisions" is often unmet for a large number of patients., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Guidelines on chronic kidney disease (CKD) recommend that nephrologists use clinical prediction models (CPMs). However, the actual use of CPMs seems limited in clinical practice. We conducted a national survey study to evaluate: 1) to what extent CPMs are used in Dutch CKD practice, 2) patients' and nephrologists' needs and preferences regarding predictions in CKD, and 3) determinants that may affect the adoption of CPMs in clinical practice., Methods: We conducted semi-structured interviews with CKD patients to inform the development of two online surveys; one for CKD patients and one for nephrologists. Survey participants were recruited through the Dutch Kidney Patient Association and the Dutch Federation of Nephrology., Results: A total of 126 patients and 50 nephrologists responded to the surveys. Most patients (89%) reported they had discussed predictions with their nephrologists. They most frequently discussed predictions regarded CKD progression: when they were expected to need kidney replacement therapy (KRT) (n = 81), and how rapidly their kidney function was expected to decline (n = 68). Half of the nephrologists (52%) reported to use CPMs in clinical practice, in particular CPMs predicting the risk of cardiovascular disease. Almost all nephrologists (98%) reported discussing expected CKD trajectories with their patients; even those that did not use CPMs (42%). The majority of patients (61%) and nephrologists (84%) chose a CPM predicting when patients would need KRT in the future as the most important prediction. However, a small portion of patients indicated they did not want to be informed on predictions regarding CKD progression at all (10-15%). Nephrologists not using CPMs (42%) reported they did not know CPMs they could use or felt that they had insufficient knowledge regarding CPMs. According to the nephrologists, the most important determinants for the adoption of CPMs in clinical practice were: 1) understandability for patients, 2) integration as standard of care, 3) the clinical relevance., Conclusion: Even though the majority of patients in Dutch CKD practice reported discussing predictions with their nephrologists, CPMs are infrequently used for this purpose. Both patients and nephrologists considered a CPM predicting CKD progression most important to discuss. Increasing awareness about existing CPMs that predict CKD progression may result in increased adoption in clinical practice. When using CPMs regarding CKD progression, nephrologists should ask whether patients want to hear predictions beforehand, since individual patients' preferences vary., (© 2023. The Author(s).)

Background: Reporting individual clinical and patient-reported outcomes to patients during consultations may add to patients' disease knowledge and activation and stimulate Shared Decision Making (SDM). These outcomes can be presented over time in a clear way by the means of dashboarding. We aimed to systematically develop a Chronic Kidney Disease (CKD) dashboard designed to support consultations, test its usability and explore conditions for optimal use in practice., Methods: For development a participatory approach with patients and healthcare professionals (HCPs) from three hospitals was used. Working groups and patient focus groups were conducted to identify needs and inform the dashboard's design. Usability was tested in patient interviews. A focus group with HCPs was held to identify conditions for optimal use of the dashboard in daily practice., Results: A dashboard was developed for CKD patients stage 3b-4 visualizing both clinical and patient-reported outcomes over time for use during consultations and accessible for patients at home. Both HCPs and patients indicated that the dashboard can: motivate patients in their treatment by providing feedback on outcomes over time; improve consultation conversations by enhanced preparation of both HCPs and patients; better inform patients, thereby facilitating shared decision making. HCPs and patients both stated that setting a topic agenda for the consultation together is important in effectively discussing the dashboard during consultations. Moreover, the dashboard should not dominate the conversation. Lastly, findings of the usability tests provided design requirements for optimal user-friendliness and clarity., Conclusions: Dashboarding can be a valuable way of reporting individual outcome information to patients and their clinicians as findings suggest it may stimulate patient activation and facilitate decision making. Co-creation with patients and HCPs was essential for successful development of the dashboard. Gained knowledge from the co-creation process can inform others wishing to develop similar digital tools for use in clinical practice., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Patient decision aids (PtDAs) support patients and clinicians in shared decision-making (SDM). Real-world outcome information may improve patients' risk perception, and help patients make decisions congruent with their expectations and values. Our aim was to develop an online PtDA to support kidney failure treatment modality decision-making, that: 1) provides patients with real-world outcome information, and 2) facilitates SDM in clinical practice., Methods: The International Patient Decision Aids Standards (IPDAS) development process model was complemented with a user-centred and convergent mixed-methods approach. Rapid prototyping was used to develop the PtDA with a multidisciplinary steering group in an iterative process of co-creation. The results of an exploratory evidence review and a needs-assessment among patients, caregivers, and clinicians were used to develop the PtDA. Seven Dutch teaching hospitals and two national Dutch outcome registries provided real-world data on selected outcomes for all kidney failure treatment modalities. Alpha and beta testing were performed to assess the prototype and finalise development. An implementation strategy was developed to guide implementation of the PtDA in clinical practice., Results: The 'Kidney Failure Decision Aid' consists of three components designed to help patients and clinicians engage in SDM: 1) a paper hand-out sheet, 2) an interactive website, and 3) a personal summary sheet. A 'patients-like-me' infographic was developed to visualise survival probabilities for each treatment modality on the website. Other treatment outcomes were incorporated as event rates (e.g. hospitalisation rates) or explained in text (e.g. the flexibility of each treatment modality). No major revisions were needed after alpha and beta testing. During beta testing, some patients ignored the survival probabilities because they considered these too confronting. Nonetheless, patients agreed that every patient has the right to choose whether they want to view this information. Patients and clinicians believed that the PtDA would help patients make informed decisions, and that it would support values- and preferences-based decision-making. Implementation of the PtDA has started in October 2020., Conclusions: The 'Kidney Failure Decision Aid' was designed to facilitate SDM in clinical practice and contains real-world outcome information on all kidney failure treatment modalities. It is currently being investigated for its effects on SDM in a clinical trial., (© 2022. The Author(s).)

Background: COVID-19 is associated with increased morbidity and mortality in patients with chronic kidney disease (CKD) stages G4-G5, on dialysis or after kidney transplantation (kidney replacement therapy, KRT). SARS-CoV-2 vaccine trials do not elucidate if SARS-CoV-2 vaccination is effective in these patients. Vaccination against other viruses is known to be less effective in kidney patients. Our objective is to assess the efficacy and safety of various types of SARS-CoV-2 vaccinations in patients with CKD stages G4-G5 or on KRT., Methods: In this national prospective observational cohort study we will follow patients with CKD stages G4-G5 or on KRT (n = 12,000) after SARS-CoV-2 vaccination according to the Dutch vaccination program. Blood will be drawn for antibody response measurements at day 28 and month 6 after completion of vaccination. Patient characteristics and outcomes will be extracted from registration data and questionnaires during 2 years of follow-up. Results will be compared with a control group of non-vaccinated patients. The level of antibody response to vaccination will be assessed in subgroups to predict protection against COVID-19 breakthrough infection., Results: The primary endpoint is efficacy of SARS-CoV-2 vaccination determined as the incidence of COVID-19 after vaccination. Secondary endpoints are the antibody based immune response at 28 days after vaccination, the durability of this response at 6 months after vaccination, mortality and (serious) adverse events., Conclusion: This study will fulfil the lack of knowledge on efficacy and safety of SARS-CoV-2 vaccination in patients with CKD stages G4-G5 or on KRT., Trial Registration: The study protocol has been registered in clinicaltrials.gov ( NCT04841785 ). Current knowledge about this subject COVID-19 has devastating impact on patients with CKD stages G4-G5, on dialysis or after kidney transplantation. Effective SARS-CoV-2 vaccination is very important in these vulnerable patient groups. Recent studies on vaccination in these patient groups are small short-term studies with surrogate endpoints. Contribution of this study Assessment of incidence and course of COVID-19 after various types of SARS-CoV-2 vaccination during a two-year follow-up period in not only patients on dialysis or kidney transplant recipients, but also in patients with CKD stages G4-G5. Quantitative analysis of antibody response after SARS-CoV-2 vaccination and its relationship with incidence and course of COVID-19 in patients with CKD stages G4-G5, on dialysis or after kidney transplantation compared with a control group. Monitoring of (serious) adverse events and development of anti-HLA antibodies. Impact on practice or policy Publication of the study design contributes to harmonization of SARS-CoV-2 vaccine study methodology in kidney patients at high-risk for severe COVID-19. Data on efficacy of SARS-CoV-2 vaccination in patients with CKD will provide guidance for future vaccination policy., (© 2022. The Author(s).)

Background: Invasive mechanical ventilation is the treatment of choice in COVID-19 patients when hypoxemia persists, despite maximum conventional oxygen administration. Some frail patients with severe hypoxemic respiratory failure are deemed not eligible for invasive mechanical ventilation., Objectives: To investigate whether High-flow nasal cannula (HFNC) in the wards could serve as a rescue therapy in these frail patients., Methods: This retrospective cohort study included frail COVID-19 patients admitted to the hospital between March 9th and May 1st 2020. HFNC therapy was started in the wards. The primary endpoint was the survival rate at hospital discharge., Results: Thirty-two patients with a median age of 79.0 years (74.5-83.0) and a Clinical Frailty Score of 4 out of 9 (3-6) were included. Only 6% reported HFNC tolerability issues. The overall survival rate was 25% at hospital discharge., Conclusions: This study suggests that, when preferred, HFNC in the wards could be a potential rescue therapy for respiratory failure in vulnerable COVID-19 patients., Competing Interests: Declaration of Competing interests The authors declare that they have no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Metabolic syndrome in patients with morbid obesity causes a higher cardiovascular morbidity, eventually leading to left ventricular hypertrophy and decreased left ventricular ejection fraction (LVEF). Roux-en-Y gastric bypass (RYGB) is considered the gold standard modality for treatment of morbid obesity and might even lead to improved cardiac function. Our objective is to investigate whether cardiac function in patients with morbid obesity improves after RYGB., Materials and Methods: In this single center pilot study, 15 patients with an uneventful cardiac history who underwent RYGB were included from May 2015 to March 2016. Cardiac function was measured by cardiac magnetic resonance imaging (CMRI), performed preoperatively and 3, 6, and 12 months postoperative. LVEF and myocardial mass and cardiac output were measured., Results: A total of 13 patients without decreased LVEF preoperative completed follow-up (mean age 37, 48.0 ± 8.8). There was a significant decrease of cardiac output 12 months postoperative (8.3 ± 1.8 preoperative vs. 6.8 ± 1.8 after 12 months, P = 0.001). Average myocardial mass declined by 15.2% (P < 0.001). After correction for body surface area (BSA), this appeared to be non-significant (P = 0.36). There was a significant improvement of LVEF/BSA at 6 and 12 months postoperative (26.2 ± 4.1 preoperative vs. 28.4 ± 3.4 and 29.2 ± 3.6 respectively, both P = 0.002). Additionally, there was a significant improvement of stroke volume/BSA 12 months after surgery (45.8 ± 8.0 vs. 51.9 ± 10.7, P = 0.033)., Conclusion: RYGB in patients with morbid obesity with uneventful history of cardiac disease leads to improvement of cardiac function.

Protein-bound uremic toxins (PBUTs) are predominantly excreted by renal tubular secretion and hardly removed by traditional hemodialysis (HD). Accumulation of PBUTs is proposed to contribute to the increased morbidity and mortality of patients with end-stage kidney disease (ESKD). Preserved PBUT excretion in patients with residual kidney function (RKF) and/or increased PBUT clearance with improved dialysis techniques might improve the prognosis of patients with ESKD. The aims of this study are to explore determinants of PBUTs in HD patients, and investigate whether hemodiafiltration (HDF) lowers PBUT plasma concentrations, and whether PBUTs are related to the outcome. Predialysis total plasma concentrations of kynurenine, kynurenic acid, indoxyl sulfate, indole-3-acetic acid, p-cresyl sulfate, p-cresyl glucuronide, and hippuric acid were measured by UHPLC-MS at baseline and after 6 months of follow-up in the first 80 patients participating in the CONvective TRAnsport Study (CONTRAST), a randomized controlled trial that compared the effects of online HDF versus low-flux HD on all-cause mortality and new cardiovascular events. RKF was inversely related to kynurenic acid ( p < 0.001), indoxyl sulfate ( p = 0.001), indole-3-acetic acid ( p = 0.024), p-cresyl glucuronide ( p = 0.004) and hippuric acid ( p < 0.001) plasma concentrations. Only indoxyl sulfate decreased by 8.0% (-15.3 to 34.6) in patients treated with HDF and increased by 11.9% (-15.4 to 31.9) in HD patients after 6 months of follow-up (HDF vs. HD: p = 0.045). No independent associations were found between PBUT plasma concentrations and either risk of all-cause mortality or new cardiovascular events. In summary, in the current population, RKF is an important determinant of PBUT plasma concentrations in HD patients. The addition of convective transport did not consistently decrease PBUT plasma concentrations and no relation was found between PBUTs and cardiovascular endpoints.

Background: C-type natriuretic peptide (CNP) and its co-product N-terminal proCNP (NTproCNP) have been associated with beneficial effects on the cardiovascular system. In prevalent dialysis patients, however, a relation between NTproCNP and mortality has not yet been investigated. Furthermore, as a middle molecular weight substance, its concentration might be influenced by dialysis modality., Methods: In a cohort of patients treated with haemodialysis (HD) or haemodiafiltration (HDF), levels of NTproCNP were measured at baseline and 6, 12, 24 and 36 months. The relation between serum NTproCNP and mortality and the relation between the 6-month rate of change of NTproCNP and mortality were analysed using Cox regression models. For the longitudinal analyses, linear mixed models were used., Results: In total, 406 subjects were studied. The median baseline serum NTproCNP was 93 pmol/L and the median follow-up was 2.97 years. No relation between baseline NTproCNP or its rate of change over 6 months and mortality was found. NTproCNP levels remained stable in HD patients, whereas NTproCNP decreased significantly in HDF patients. The relative decline depended on the magnitude of the convection volume., Conclusions: In our study, levels of NTproCNP appear strongly elevated in prevalent dialysis patients. Second, while NTproCNP remains unaltered in HD patients, its levels decline in individuals treated with HDF, with the decline dependent on the magnitude of the convection volume. Third, NTproCNP is not related to mortality in this population. Thus NTproCNP does not seem to be a useful marker for mortality risk in dialysis patients., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA.)

Connective tissue growth factor (CTGF) plays a key role in the pathogenesis of tissue fibrosis. The aminoterminal fragment of CTGF is a middle molecule that accumulates in chronic kidney disease. The aims of this study are to explore determinants of plasma CTGF in hemodialysis (HD) patients, investigate whether CTGF relates to all-cause mortality in HD patients, and investigate whether online-hemodiafiltration (HDF) lowers CTGF. Data from 404 patients participating in the CONvective TRAnsport STudy (CONTRAST) were analyzed. Patients were randomized to low-flux HD or HDF. Pre-dialysis CTGF was measured by sandwich ELISA at baseline, after six and 12 months. CTGF was inversely related in multivariable analysis to glomerular filtration rate (GFR) ( p < 0.001) and positively to cardiovascular disease (CVD) ( p = 0.006), dialysis vintage ( p < 0.001), interleukin-6 ( p < 0.001), beta-2-microglobulin ( p = 0.045), polycystic kidney disease ( p < 0.001), tubulointerstitial nephritis ( p = 0.002), and renal vascular disease ( p = 0.041). Patients in the highest quartile had a higher mortality risk compared to those in the lowest quartile (HR 1.7, 95% CI: 1.02-2.88, p = 0.043). HDF lowered CTGF with 4.8% between baseline and six months, whereas during HD, CTGF increased with 4.9% ( p < 0.001). In conclusion, in HD patients, CTGF is related to GFR, CVD and underlying renal disease and increased the risk of all-cause mortality. HDF reduces CTGF.

Background/aims: In hemodialysis (HD) patients, the bromcresol green (BCG) assay overestimates, whereas the bromcresol purple (BCP) assay underestimates albumin concentration. Since corrected calcium concentrations depend on albumin, the albumin assay may have implications for the management of bone mineral disorders., Methods: A subset of patients from CONTRAST, a cohort of prevalent HD patients, was analyzed. Bone mineral parameters and prescription of medication were compared between patients in whom albumin was assessed by BCP versus BCG., Results: Albumin was assessed by BCP in 331 patients (9 of 25 centers) and by BCG in 175 patients (16 of 25 centers). Albumin was the lowest in the BCP group (34.5 ± 4.2 vs. 40.3 ± 3.1 g/L; p < 0.0005). Measured calcium levels and the prescription of calcium-based phosphate binders were similar in both groups. Corrected calcium levels, however, were markedly higher in the BCP group (2.45 ± 0.18 vs. 2.33 ± 0.18 mmol/L; p < 0.0005)., Conclusion: These findings suggest that calcium levels are not corrected for albumin in clinical practice when considering the prescription of calcium-free or calcium-based phosphate-binders in dialysis patients., (© 2018 The Author(s) Published by S. Karger AG, Basel.)

Background: Physical, cognitive and psychosocial functioning are frequently impaired in dialysis patients and impairment in these domains relates to poor outcome. The aim of this analysis was to compare the prevalence of impairment as measured by the Kidney Disease Quality of Life- Short Form (KDQOL-SF) subscales between the different age categories and to assess whether the association of these subscales with mortality differs between younger and older dialysis patients., Methods: This study included data from 714 prevalent hemodialysis patients, from 26 centres, who were enrolled in the CONvective TRAnsport STudy (CONTRAST NCT00205556, 09-12-2005). Baseline HRQOL domains were evaluated for patients <65 years, 65-74 years and over 75 years. Multivariable Cox proportional hazards analyses were performed to assess the relation between the separate domains and 2-year mortality., Results: Emotional health was higher in patients over the age of 75 compared to younger patients (mean level 71, 73 and 77 for increasing age categories respectively, p = 0.02), whilst physical functioning was significantly lower in older patients (mean level 60, 48 and 40, p < 0.01). A low level of physical functioning (Hazard Ratio (HR) 1.72 [95%Confidence Interval (CI) 1.02-2.73]), emotional health (HR 1.85 [95% 1.30-2.63]), and social functioning (HR 1.59 [95% CI 1.12-2.26]), was individually associated with an increased 2-year mortality within the whole population. The absence of effect modification suggests no evidence for different relations within the older age groups., Conclusions: In dialysis patients, older age is associated with lower levels of physical functioning, whilst the level of emotional health is not associated with age. KDQOL-SF domains physical functioning, emotional health and social functioning are independently associated with mortality in prevalent younger and older hemodialysis patients.

Background: The glycoprotein sclerostin (Scl; 22 kDa), which is involved in bone metabolism, may play a role in vascular calcification in haemodialysis (HD) patients. In the present study, we investigated the relation between serum Scl (sScl) and mortality. The effects of dialysis modality and the magnitude of the convection volume in haemodiafiltration (HDF) on sScl were also investigated., Methods: In a subset of patients from the CONTRAST study, a randomized controlled trial comparing HDF with HD, sScl was measured at baseline and at intervals of 6, 12, 24 and 36 months. Patients were divided into quartiles, according to their baseline sScl. The relation between time-varying sScl and mortality with a 4-year follow-up period was investigated using crude and adjusted Cox regression models. Linear mixed models were used for longitudinal measurements of sScl., Results: The mean (±standard deviation) age of 396 test subjects was 63.6 (±13.9 years), 61.6% were male and the median follow-up was 2.9 years. Subjects with the highest sScl had a lower mortality risk than those with the lowest concentrations [adjusted hazard ratio 0.51 (95% confidence interval, CI, 0.31-0.86, P = 0.01)]. Stratified models showed a stable sScl in patients treated with HD (Δ +2.9 pmol/L/year, 95% CI -0.5 to +6.3, P = 0.09) and a decreasing concentration in those treated with HDF (Δ -4.5 pmol/L/year, 95% CI -8.0 to -0.9, P = 0.02). The relative change in the latter group was related to the magnitude of the convection volume., Conclusions: (i) A high sScl is associated with a lower mortality risk in patients with end-stage kidney disease; (ii) treatment with HDF causes sScl to fall; and (iii) the relative decline in patients treated with HDF is dependent on the magnitude of the convection volume., (© The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: The aim was to test the effectiveness of early home-based group education on knowledge and communication about renal replacement therapy (RRT)., Methods: We conducted a randomized controlled trial using a cross-over design among 80 end-stage renal disease (ESRD) patients. Between T0 and T1 (weeks 1-4) Group 1 received the intervention and Group 2 received standard care. Between T1 and T2 (weeks 5-8) Group 1 received standard care and Group 2 received the intervention. The intervention was a group education session on RRT options held in the patient's home given by social workers. Patients invited members from their social network to attend. Self-report questionnaires were used at T0, T1 and T2 to measure patients' knowledge and communication, and concepts from the Theory of Planned Behaviour such as attitude. Comparable questionnaires were completed pre-post intervention by 229 attendees. Primary RRT was registered up to 2 years post-intervention. Multilevel linear modelling was used to analyse patient data and paired t-tests for attendee data., Results: Statistically significant increases in the primary targets knowledge and communication were found among patients and attendees after receiving the intervention. The intervention also had a significant effect in increasing positive attitude toward living donation and haemodialysis. Of the 80 participants, 49 underwent RRT during follow-up. Of these, 34 underwent a living donor kidney transplant, of which 22 were pre-emptive., Conclusions: Early home-based group education supports informed decision-making regarding primary RRT for ESRD patients and their social networks and may remove barriers to pre-emptive transplantation., (© The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Objective: Protein-energy wasting (PEW), a state of decreased bodily protein and energy fuels, is highly prevalent among hemodialysis patients. The best method to determine PEW, however, remains debated. As an independent, negative association between PEW and quality of life (QOL) has been demonstrated, establishing which nutrition-related test correlates best with QOL may help to identify how PEW should preferably be assessed., Design and Methods: Data were used from CONTRAST, a cohort of end-stage kidney disease patients. At baseline, Subjective Global Assessment (SGA), Malnutrition Inflammation Score (MIS), Geriatric Nutritional Risk Index, composite score on protein-energy nutritional status, normalized protein nitrogen appearance, body mass index, serum albumin, and serum creatinine were determined. QOL was assessed by the Kidney Disease Quality of Life Short Form 1.3. The present study reports on 2 general and 11 kidney disease-specific QOL scores. Spearman's rho (ρ) was calculated to determine correlations between nutrition-related tests and QOL domains. Twelve months after randomization, a sensitivity analysis was performed to test the robustness of the results., Results: Of 714 patients, 489 representative subjects were available for analysis. All tests correlated with the Physical Component Score, except body mass index. Only SGA and MIS correlated significantly with the Mental Component Score. SGA correlated significantly with 10 of 11 kidney disease-specific QOL domains. The MIS not only correlated significantly with all (11) kidney disease-specific QOL domains but also with higher correlation coefficients., Conclusion: Of the 8 investigated nutrition-related tests, only MIS correlates with all QOL domains (13 of 13) with the strongest associations., (Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Despite suggestions that higher serum magnesium (Mg) levels are associated with improved outcome, the association with mortality in European hemodialysis (HD) patients has only scarcely been investigated. Furthermore, data on the association between serum Mg and sudden death in this patient group is limited. Therefore, we evaluated Mg in a post-hoc analysis using pooled data from the CONvective TRAnsport STudy (CONTRAST, NCT00205556), a randomized controlled trial (RCT) evaluating the survival risk in dialysis patients on hemodiafiltration (HDF) compared to HD with a mean follow-up of 3.1 years. Serum Mg was measured at baseline and 6, 12, 24 and 36 months thereafter. Cox proportional hazards models, adjusted for confounders using inverse probability weighting, were used to estimate hazard ratios (HRs) of baseline serum Mg on all-cause mortality, cardiovascular mortality, non-cardiovascular mortality and sudden death. A generalized linear mixed model was used to investigate Mg levels over time. Out of 714 randomized patients, a representative subset of 365 (51%) were analyzed in the present study. For every increase in baseline serum Mg of 0.1 mmol/L, the HR for all-cause mortality was 0.85 (95% CI 0.77-94), the HR for cardiovascular mortality 0.73 (95% CI 0.62-0.85) and for sudden death 0.76 (95% CI 0.62-0.93). These findings did not alter after extensive correction for potential confounders, including treatment modality. Importantly, no interaction was found between serum phosphate and serum Mg. Baseline serum Mg was not related to non-cardiovascular mortality. Mg decreased slightly but statistically significant over time (Δ -0.011 mmol/L/year, 95% CI -0.017 to -0.009, p = 0.03). In short, serum Mg has a strong, independent association with all-cause mortality, cardiovascular mortality and sudden death in European HD patients. Serum Mg levels decrease slightly over time.

Objective: Protein-energy wasting (PEW) describes a state of decreased protein and energy fuels and is highly prevalent in hemodialysis patients. As PEW is associated with mortality, it should be detected accurately and easily. This study investigated which nutrition-related test predicts mortality and morbidity best in hemodialysis patients., Design and Subjects: Data were used from CONTRAST, a cohort of end-stage kidney disease patients. Subjective Global Assessment (SGA), Malnutrition Inflammation Score (MIS), Geriatric Nutritional Risk Index (GNRI), composite score of Protein-Energy Nutritional Status (cPENS), serum albumin, serum creatinine, body mass index, and normalized protein nitrogen appearance rate were assessed at baseline. End points were all-cause mortality, cardiovascular events, and infection. Discriminative value of every test was assessed with Harrell's C statistic and calibration tested using the Hosmer-Lemeshow goodness-of-fit test. Ultimately, in every test, 4 groups were created to compare (1) hazard ratios (HR; worst vs best group), (2) HR increase per group, and (3) HR of worst group versus other groups., Results: In total, 489 patients were analyzed. Median follow-up was 2.97 years (interquartile range, 1.67-4.47 years). MIS, GNRI, albumin, and creatinine discriminated all-cause mortality equally. SGA, cPENS, body mass index, and normalized protein nitrogen appearance were inferior. cPENS and creatinine were inadequately calibrated. Of the remaining tests, GNRI predicted mortality less when comparing HRs. MIS and albumin predicted mortality equally well. In a subanalysis, these also predicted infection equally well, but MIS predicted cardiovascular events better., Conclusion: Of the 8 investigated nutrition-related tests, MIS and albumin predict mortality best in hemodialysis patients. As one has no added value over the other, we conclude that mortality is most easily predicted in hemodialysis patients by serum albumin., (Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: 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., Patients and Methods: 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., Results: 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)., Conclusions: HDF as compared to HD did not result in a reduced risk of infections, larger studies are needed to confirm our findings., Trial Registration: ClinicalTrials.gov NCT00205556.

Background: Magnesium (Mg(2+)) is an essential ion for cell growth, neuroplasticity and muscle contraction. Blood Mg(2+) levels <0.7 mmol/L may cause a heterogeneous clinical phenotype, including muscle cramps and epilepsy and disturbances in K(+) and Ca(2+) homeostasis. Over the last decade, the genetic origin of several familial forms of hypomagnesaemia has been found. In 2000, mutations in FXYD2, encoding the γ-subunit of the Na(+)-K(+)-ATPase, were identified to cause isolated dominant hypomagnesaemia (IDH) in a large Dutch family suffering from hypomagnesaemia, hypocalciuria and chondrocalcinosis. However, no additional patients have been identified since then., Methods: Here, two families with hypomagnesaemia and hypocalciuria were screened for mutations in the FXYD2 gene. Moreover, the patients were clinically and genetically characterized., Results: We report a p.Gly41Arg FXYD2 mutation in two families with hypomagnesaemia and hypocalciuria. Interestingly, this is the same mutation as was described in the original study. As in the initial family, several patients suffered from muscle cramps, chondrocalcinosis and epilepsy. Haplotype analysis revealed an overlapping haplotype in all families, suggesting a founder effect., Conclusions: The recurrent p.Gly41Arg FXYD2 mutation in two new families with IDH confirms that FXYD2 mutation causes hypomagnesaemia. Until now, no other FXYD2 mutations have been reported which could indicate that other FXYD2 mutations will not cause hypomagnesaemia or are embryonically lethal., (© The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background/aims: Treatment time is associated with survival in hemodialysis (HD) patients and with convection volume in hemodiafiltration (HDF) patients. High-volume HDF is associated with improved survival. Therefore, we investigated whether this survival benefit is explained by treatment time., Methods: Participants were subdivided into four groups: HD and tertiles of convection volume in HDF. Three Cox regression models were fitted to calculate hazard ratios (HRs) for mortality of HDF subgroups versus HD: (1) crude, (2) adjusted for confounders, (3) model 2 plus mean treatment time. As the only difference between the latter models is treatment time, any change in HRs is due to this variable., Results: 114/700 analyzed individuals were treated with high-volume HDF. HRs of high-volume HDF are 0.61, 0.62 and 0.64 in the three models, respectively (p values <0.05). Confidence intervals of models 2 and 3 overlap., Conclusion: The survival benefit of high-volume HDF over HD is independent of treatment time., (© 2015 S. Karger AG, Basel.)

Background/aims: Both all-cause and cardiovascular mortality risks are extremely high in patients with end-stage kidney disease (ESKD). Sudden death accounts for approximately one-quarter of all fatal events. Left ventricular hypertrophy (LVH) is a known risk factor for mortality and can be divided in 2 types: concentric and eccentric. This study evaluated possible differences in all-cause mortality, cardiovascular mortality and sudden death between prevalent ESKD patients with concentric and eccentric LVH., Methods: Participants of the CONvective TRAnsport STudy (CONTRAST) who underwent transthoracic echocardiography (TTE) at baseline were analyzed. In patients with LVH, a relative wall thickness of ≤0.42 was considered eccentric and >0.42 was considered concentric hypertrophy. Cox proportional hazards models, adjusted for potential confounders, were used to calculate hazard ratios (HRs) of patients with eccentric LVH versus patients with concentric LVH for all-cause mortality, cardiovascular mortality and sudden death., Results: TTE was performed in 328 CONTRAST participants. LVH was present in 233 participants (71%), of which 87 (37%) had concentric LVH and 146 (63%) eccentric LVH. The HR for all-cause mortality of eccentric versus concentric LVH was 1.14 (p = 0.52), 1.79 (p = 0.12) for cardiovascular mortality and 4.23 (p = 0.02) for sudden death in crude analyses. Propensity score-corrected HR for sudden death in patients with eccentric LVH versus those with concentric LVH was 5.22 (p = 0.03)., Conclusions: (1) The hazard for all-cause mortality, cardiovascular mortality and sudden death is markedly increased in patients with LVH. (2) The sudden death risk is significantly higher in ESKD patients with eccentric LVH compared to subjects with concentric LVH., (© 2015 S. Karger AG, Basel.)

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.

Unlabelled: 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., Trial Registration: ClinicalTrials.gov NCT00205556.

Background and Objective: Increased left ventricular mass (LVM), low ventricular ejection fraction (EF), and high pulse-wave velocity (PWV) relate to overall and cardiovascular mortality in patients with ESRD. The aim of this study was to determine the effect of online hemodiafiltration (HDF) versus low-flux hemodialysis (HD) on LVM, EF, and PWV., Design, Setting, Participants, & Measurements: Echocardiography was used to assess LVM and EF in 342 patients in the CONvective TRAnsport STudy followed for up to 4 years. PWV was measured in 189 patients for up to 3 years. Effect of HDF versus HD on LVM, EF, and PWV was evaluated using linear mixed models., Results: Patients had a mean age of 63 years, and 61% were male. At baseline, median LVM was 227 g (interquartile range [IQR], 183-279 g), and median EF was 65% (IQR, 55%-72%). Median PWV was 9.8 m/s (IQR, 7.5-12.0 m/s). There was no significant difference between the HDF and HD treatment groups in rate of change in LVM (HDF: change, -0.9 g/yr [95% confidence interval (95% CI), -8.9 to 7.7 g]; HD: change, 12.5 g/yr [95% CI, -3.0 to 27.5 g]; P for difference=0.13), EF (HDF: change, -0.3%/yr [95% CI, -2.3% to 1.8%]; HD: change, -3.4%/yr [95% CI, -5.9% to -0.9%]; P=0.17), or PWV (HDF: change, -0.0 m/s per year [95% CI, -0.4 to 0.4 m/s); HD: change, 0.0 m/s per year [95% CI, -0.3 to 0.2 m/s]; P=0.89). No differences in rate of change between treatment groups were observed for subgroups of age, sex, residual kidney function, dialysis vintage, history of cardiovascular disease, diabetes, or convection volume., Conclusions: Treatment with online HDF did not affect changes in LVM, EF, or PWV over time compared with HD.

Background and Objectives: Left ventricular mass (LVM) is known to be related to overall and cardiovascular mortality in end stage kidney disease (ESKD) patients. The aims of the present study are 1) to determine whether LVM is associated with mortality and various cardiovascular events and 2) to identify determinants of LVM including biomarkers of inflammation and fibrosis., Design Setting Participants & Measurements: Analysis was performed with data of 327 ESKD patients, a subset from the CONvective TRAnsport STudy (CONTRAST). Echocardiography was performed at baseline. Cox regression analysis was used to assess the relation of LVM tertiles with clinical events. Multivariable linear regression models were used to identify factors associated with LVM., Results: Median age was 65 (IQR: 54-73) years, 203 (61%) were male and median LVM was 227 (IQR: 183-279) grams. The risk of all-cause mortality (hazard ratio (HR) = 1.73, 95% CI: 1.11-2.99), cardiovascular death (HR = 3.66, 95% CI: 1.35-10.05) and sudden death (HR = 13.06; 95% CI: 6.60-107) was increased in the highest tertile (>260 grams) of LVM. In the multivariable analysis positive relations with LVM were found for male gender (B = 38.8±10.3), residual renal function (B = 17.9±8.0), phosphate binder therapy (B = 16.9±8.5), and an inverse relation for a previous kidney transplantation (B = -41.1±7.6) and albumin (B = -2.9±1.1). Interleukin-6 (Il-6), high-sensitivity C-reactive protein (hsCRP), hepcidin-25 and connective tissue growth factor (CTGF) were not related to LVM., Conclusion: We confirm the relation between a high LVM and outcome and expand the evidence for increased risk of sudden death. No relationship was found between LVM and markers of inflammation and fibrosis., Trial Registration: Controlled-Trials.com ISRCTN38365125.

Background and Objectives: Inflammation and malnutrition are important features in patients with ESRD; however, data on changes in these parameters over time are scarce. This study aimed to gain insight into changes over time in serum albumin, body mass index, high-sensitivity C-reactive protein, and IL-6 in patients with ESRD and aimed to identify clinical risk factors for deterioration of these parameters., Design, Setting, Participants, & Measurements: Data were analyzed from the Convective Transport Study, a randomized controlled trial conducted from June 2004 to January 2011, in which 714 patients with chronic ESRD were randomized to either online hemodiafiltration or low-flux hemodialysis. Albumin and body mass index were measured up to 6 years and predialysis C-reactive protein and IL-6 were measured up to 3 years in a subset of 405 participants. Rates of change in these parameters over time were estimated across strata of predefined risk factors with linear mixed-effects models., Results: Albumin and body mass index decreased and C-reactive protein and IL-6 increased over time. For every incremental year of age at baseline, the yearly excess decline in albumin was 0.003 g/dl (-0.004 to -0.002; P<0.001) and the excess decline in body mass index was 0.02 kg/m(2) per year (-0.02 to -0.01; P<0.001). In patients with diabetes mellitus, there was a yearly excess decline of 0.05 g/dl in albumin (-0.09 to -0.02; P=0.002). Compared with women, men had an excess decline of 0.03 g/dl per year in albumin (-0.06 to -0.001; P=0.05) and an excess increase of 11.6% per year in IL-6 (0.63%-23.6%; P=0.04)., Conclusions: Despite guideline-based care, all inflammatory and nutritional parameters worsened over time. The deterioration of some of these parameters was more pronounced in men, older patients, and patients with diabetes mellitus. Special focus on the nutritional status of at-risk patients by individualizing medical care might improve their prognosis.

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.)

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 non-fatal 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.

Background: Despite the growing interest in haemodiafiltration (HDF), there is no information on the costs and cost-utility of this dialysis modality yet. It was therefore our objective to study the cost-utility of HDF versus haemodialysis (HD)., Methods: A cost-utility analysis was performed using a Markov model. It included data from the Convective Transport Study (CONTRAST), a randomized controlled trial that compared online HDF with low-flux HD. Costs were estimated using a societal perspective. Probabilistic sensitivity analyses were performed to study uncertainty., Results: Total annual costs for HDF and HD were €88 622±19,272 and €86,086±15,945, respectively (in 2009 euros). When modelled over a 5-year period, the incremental cost per quality-adjusted life year (QALY) of HDF versus HD was €287,679. Sensitivity analyses revealed that this amount will not fall below €140,000, even under the most favourable assumptions like a high-convection volume (>20.3 L)., Conclusions: Based on accepted societal willingness-to-pay thresholds, HDF cannot be considered a cost-effective treatment for patients with end-stage renal disease at present. Apparently, minor additional costs of HDF are not counterbalanced by a relevant QALY gain.

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.

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.

In patients with ESRD, the effects of online hemodiafiltration on all-cause mortality and cardiovascular events are unclear. In this prospective study, we randomly assigned 714 chronic hemodialysis patients to online postdilution hemodiafiltration (n=358) or to continue low-flux hemodialysis (n=356). The primary outcome measure was all-cause mortality. The main secondary endpoint was a composite of major cardiovascular events, including death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, therapeutic coronary intervention, therapeutic carotid intervention, vascular intervention, or amputation. After a mean 3.0 years of follow-up (range, 0.4-6.6 years), we did not detect a significant difference between treatment groups with regard to all-cause mortality (121 versus 127 deaths per 1000 person-years in the online hemodiafiltration and low-flux hemodialysis groups, respectively; hazard ratio, 0.95; 95% confidence interval, 0.75-1.20). The incidences of cardiovascular events were 127 and 116 per 1000 person-years, respectively (hazard ratio, 1.07; 95% confidence interval, 0.83-1.39). Receiving high-volume hemodiafiltration during the trial associated with lower all-cause mortality, a finding that persisted after adjusting for potential confounders and dialysis facility. In conclusion, this trial did not detect a beneficial effect of hemodiafiltration on all-cause mortality and cardiovascular events compared with low-flux hemodialysis. On-treatment analysis suggests the possibility of a survival benefit among patients who receive high-volume hemodiafiltration, although this subgroup finding requires confirmation.

Background: Connective tissue growth factor (CTGF) has a key role in the pathogenesis of renal and cardiac fibrosis. Its amino-terminal fragment (N-CTGF), the predominant form of CTGF detected in plasma, has a molecular weight in the middle molecular range (18 kDa). However, it is unknown whether N-CTGF is a uremic retention solute that accumulates in chronic kidney disease (CKD) due to decreased renal clearance and whether it can be removed by hemodiafiltration., Study Design: 4 observational studies in patients and 2 pharmacokinetic studies in rodents., Setting & Participants: 4 single-center studies. First study (cross-sectional): 88 patients with CKD not receiving kidney replacement therapy. Second study (cross-sectional): 23 patients with end-stage kidney disease undergoing low-flux hemodialysis. Third study: 9 kidney transplant recipients before and 6 months after transplant. Fourth study: 11 low-flux hemodialysis patients and 12 hemodiafiltration patients before and after one dialysis session., Predictor: First, second, and third study: (residual) glomerular filtration rate (GFR). Fourth study: dialysis modality., Outcomes & Measurements: Plasma (N-)CTGF concentrations, measured by enzyme-linked immunosorbent assay., Results: In patients with CKD, we observed an independent association between plasma CTGF level and estimated GFR (β = -0.72; P < 0.001). In patients with end-stage kidney disease, plasma CTGF level correlated independently with residual kidney function (β = -0.55; P = 0.046). Successful kidney transplant resulted in a decrease in plasma CTGF level (P = 0.008) proportional to the increase in estimated GFR. Plasma CTGF was not removed by low-flux hemodialysis, whereas it was decreased by 68% by a single hemodiafiltration session (P < 0.001). Pharmacokinetic studies in nonuremic rodents confirmed that renal clearance is the major elimination route of N-CTGF., Limitations: Observational studies with limited number of patients. Fourth study: nonrandomized, evaluation of the effect of one session; randomized longitudinal study is warranted., Conclusion: Plasma (N-)CTGF is eliminated predominantly by the kidney, accumulates in CKD, and is decreased substantially by a single hemodiafiltration session., (Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Hemodialysis patients undergo frequent and long visits to the clinic to receive adequate dialysis treatment, medical guidance, and support. This may affect health-related quality of life (HRQOL). Although HRQOL is a very important management aspect in hemodialysis patients, there is a paucity of information on the differences in HRQOL between centers. We set out to assess the differences in HRQOL of hemodialysis patients between dialysis centers and explore which modifiable center characteristics could explain possible differences., Methods: This cross-sectional study evaluated 570 hemodialysis patients from 24 Dutch dialysis centers. HRQOL was measured with the Kidney Disease Quality Of Life-Short Form (KDQOL-SF)., Results: After adjustment for differences in case-mix, three HRQOL domains differed between dialysis centers: the physical composite score (PCS, P = 0.01), quality of social interaction (P = 0.04), and dialysis staff encouragement (P = 0.001). These center differences had a range of 11-21 points on a scale of 0-100, depending on the domain. Two center characteristics showed a clinical relevant relation with patients' HRQOL: dieticians' fulltime-equivalent and the type of dialysis center., Conclusion: This study showed that clinical relevant differences exist between dialysis centers in multiple HRQOL domains. This is especially remarkable as hemodialysis is a highly standardized therapy.

Background/aims: Patients value health-related quality of life (HRQOL) over survival. It was our aim to study the relation between attainment of widely accepted performance targets and HRQOL in hemodialysis patients., Methods: This study included baseline data from 715 hemodialysis patients from 29 dialysis centers. Six clinical performance targets, as recommended by the Kidney Disease Outcomes Quality Initiative (KDOQI), were evaluated: single-pool Kt/V (≥1.2), hemoglobin (11-13 g/dl), vascular access (fistula), phosphorus (2.3-4.5 mg/dl), parathyroid hormone (150-300 pg/ml), and blood pressure (predialysis <140/90 and postdialysis <130/ 80 mm Hg)., Results: After correction for case-mix and multiple comparisons, no association was found between the 6 KDOQI clinical performance targets and the 14 HRQOL domains, or between the number of performance targets reached and HRQOL., Conclusion: Attainment with widely accepted clinical performance targets was not related to the HRQOL of hemodialysis patients. Hence, in clinical guidelines, HRQOL should be adopted as an explicit treatment goal for these individuals., (Copyright © 2011 S. Karger AG, Basel.)

Background/aims: Guidelines for the management of anemia and iron deficiency in chronic hemodialysis (HD) patients have been developed to standardize therapy and improve clinical outcome. The present study evaluated compliance with anemia guidelines and investigated whether differences between centers were present., Methods: Data on anemia management from patients in the baseline cohort of the CONTRAST study (NCT00205556) were analyzed. 598 chronic HD patients (62% male, age 63.6 ± 14.0 years) from 26 Dutch dialysis centers were included., Results: Mean hemoglobin (Hb) level was 11.9 ± 1.3 g/dl and Hb was ≥11.0 g/dl in 81% of the patients. Compliance with all anemia targets (Hb 11.0-12.0 g/dl, transferrin saturation ratio ≥20%, ferritin 100-500 ng/ml) was reached in 11.6% (95% CI 7.8-17.0) of the patients, with a wide range among centers (4-26%, adjusted for case mix, treatment-related factors and center-specific characteristics)., Conclusion: Compliance with anemia targets in stable HD patients was poor and showed a wide variation between treatment facilities., (Copyright © 2012 S. Karger AG, Basel.)

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.

In this article, an ethical analysis of an educational programme on renal replacement therapy options for patients and their social network is presented. The two main spearheads of this approach are: (1) offering an educational programme on all renal replacement therapy options ahead of treatment requirement and (2) a home-based approach involving the family and friends of the patient. Arguments are offered for the ethical justification of this approach by considering the viewpoint of the various stakeholders involved. Finally, reflecting on these ethical considerations, essential conditions for carrying out such a programme are outlined. The goal is to develop an ethically justified and responsible educational programme.

Background: Nowadays, as a result of more liberal selection criteria, dialysis-dependent patients have become substantially older, more likely to be female and diabetic, and have more comorbidity. The 1-year primary patency rates of arteriovenous fistulas (AVFs) are poor. To improve these results, several secondary interventions can be performed. The aim of this study was to evaluate the results after secondary interventions in patients with an upper extremity AVF., Methods: Between January 2000 and December 2008, all consecutive patients who underwent construction of an autologous upper extremity AVF were included. Patient characteristics were collected retrospectively from digital patient files and a prospectively recorded database on hemodialysis patients., Results: Between January 2000 and December 2008, 736 hemodialysis access procedures were performed. A total of 347 autologous arteriovenous fistulas (AVFs) were created in 294 patients. The mean age was 62.1 ± 14.7 years, and the majority (66%) of the patients was male. Mean follow-up of all 347 fistulas was 21.9 ± 21.6 months. During follow-up, failure occurred in 209 (60%) of the AVFs. A total of 133 of these failures were followed by a secondary intervention, of which 78 (59%) were endovascular interventions. Twenty-nine patients developed a third failure, and 25 of these patients underwent another intervention, of which 22 were percutaneous transluminal angioplasty for stenosis. Fifteen patients developed a fourth failure, and all of them underwent an intervention. One patient had 11 interventions. The 1- and 2-year primary patency rates were 46% and 36.8%, respectively. The 1- and 2-year primary assisted patency rates were 74.6% and 71.2%, respectively. The 1- and 2-year secondary patency rates were 79.2% and 77.8%, respectively., Conclusion: The primary patency rate of AVFs is disappointing. However, due to mostly endovascular secondary interventions, 2-year primary assisted and secondary patency rates of more than 70% can be obtained., (Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

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., (Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Protein-energy wasting is tightly associated with mortality in haemodialysis patients. An expert panel of the International Society of Renal Nutrition and Metabolism (ISRNM) has published a consensus on the parameters that define protein-energy nutritional status and posed the question, 'which scoring system most effectively predicts outcome?' The aim of our study was therefore to develop a composite score of protein-energy nutritional status (cPENS) and to assess its prediction of all-cause mortality., Methods: We used the data of 560 haemodialysis patients participating in the CONvective TRAnsport STudy (CONTRAST). All participants were followed for occurrence of death. Internationally recommended nutritional targets were used as components of the cPENS, including the subjective global assessment (target score ≥ 6), albumin (≥ 4.0 g/dL), normalized protein nitrogen appearance (≥ 0.8 g/kg/day), cholesterol (≥ 100 mg/dL), creatinine (≥ 10 mg/dL) and BMI (> 23 kg/m(2)). A Cox regression model was used to analyse the relation between different cPENS variants and mortality., Results: The median follow-up time was 1.4 years (max 4.2). One hundred and five patients (19%) died. A cPENS variant based on albumin, BMI, creatinine and the nPNA yielded the strongest relation with mortality (hazard ratio 0.63, 95% confidence interval 0.54-0.74, P < 0.001), after adjustments for confounders. Some of the individual parameters of the cPENS, notably albumin and creatinine, were related to mortality with similar strength and magnitude., Conclusions: In conclusion, albumin reflects mortality risk similarly to multiple nutritional parameters combined. This questions the clinical value of the proposed diagnostic criteria for protein-energy wasting.