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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]

Background: Pruritus is common in dialysis patients and associated with impaired health-related quality of life (HRQoL) and sleep disturbances. Its pathophysiology remains unclear resulting in limited treatment options and lack of treatment guidelines. The exact trajectory of pruritus after dialysis initiation nor the state of current medical treatment has been studied., Methods: Incident dialysis patients (n=1438), included in the Dutch nOcturnal and hoME dialysis Study To Improve Clinical Outcomes (DOMESTICO), were studied. Outcome parameters were prevalence of pruritus, severity of pruritus and the use of antipruritic medication, repeatedly measured during the first year of dialysis. Associations between treatment, pruritus and quality of life were longitudinally studied using linear mixed models., Results: The prevalence of pruritus ranged from 50.5% to 56.6% during the first year of dialysis. Throughout the year approximately 35% experienced persistent pruritus and 40% fluctuating pruritus. During follow-up 21.5% to 26.5% received medical treatment for pruritus. Emollients were associated with more severe pruritus (adjusted β = 0.31, 95% CI 0.15; 0.48), the remaining treatments did not show any association. Pruritus was significantly associated with lower physical and mental HRQoL (adjusted β = -2.04, 95% CI -2.78; -1.30 and β = -1.73, 95% CI -2.51; -0.94, respectively), irrespective of treatment., Conclusions: During the first year of dialysis, pruritus is highly prevalent, predominantly fluctuating, and associated with impaired HRQoL. The minority of patients received medical treatment; in our study current treatment was not associated with an improvement of pruritus. These results highlight the need for more awareness among clinicians and for the development of effective treatment options., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Nephrology.)

Background and Aims: Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV) is associated with an increased cardiovascular risk, particularly the myeloperoxidase AAV serotype (MPO-AAV). Distinct alterations in monocyte phenotypes may cause accelerated atherosclerotic disease in AAV., Methods: A cohort including 43 AAV patients and 19 healthy controls was included for downstream analyses. Extensive phenotyping of monocytes and monocyte-derived macrophages was performed using bulk RNA-sequencing and flow cytometry. An in vitro transendothelial migration assay reflecting intrinsic adhesive and migratory capacities of monocytes was employed. Subsequent sub-analyses were performed to investigate differences between serological subtypes., Results: Monocyte subset analysis showed increased classical monocytes during active disease, whereas non-classical monocytes were decreased compared to healthy controls (HC). RNA-sequencing revealed upregulation of distinct inflammatory pathways and lipid metabolism-related markers in monocytes of active AAV patients. No differences were detected in the intrinsic monocyte adhesion and migration capacity. Compared to proteinase-3(PR3)-AAV, monocytes of MPO-AAV patients in remission expressed genes related to inflammation, coagulation, platelet-binding and interferon signalling, whereas the expression of chemokine receptors indicative of acute inflammation and monocyte extravasation (i.e., CCR2 and CCR5) was increased in monocytes of PR3-AAV patients. During active disease, PR3-AAV was linked with elevated serum CRP and increased platelet counts compared to MPO-AAV., Conclusions: These findings highlight changes in monocyte subset composition and activation, but not in the intrinsic migration capacity of AAV monocytes. MPO-AAV monocytes are associated with sustained upregulation of inflammatory genes, whereas PR3-AAV monocytes exhibit chemokine receptor upregulation. These molecular changes may play a role in elevating cardiovascular risk as well as in the underlying pathophysiology of AAV., 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 © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Because anti-neutrophil cytoplasmatic antibody (ANCA)-associated vasculitis (AAV) is a rare, life-threatening, auto-immune disease, conducting research is difficult but essential. A long-lasting challenge is to identify rare AAV patients within the electronic-health-record (EHR)-system to facilitate real-world research. Artificial intelligence (AI)-search tools using natural language processing (NLP) for text-mining are increasingly postulated as a solution., Methods: We employed an AI-tool that combined text-mining with NLP-based exclusion, to accurately identify rare AAV patients within large EHR-systems (>2.000.000 records). We developed an identification method in an academic center with an established AAV-training set (n = 203) and validated the method in a non-academic center with an AAV-validation set (n = 84). To assess accuracy anonymized patient records were manually reviewed., Results: Based on an iterative process, a text-mining search was developed on disease description, laboratory measurements, medication and specialisms. In the training center, 608 patients were identified with a sensitivity of 97.0 % (95%CI [93.7, 98.9]) and positive predictive value (PPV) of 56.9 % (95%CI [52.9, 60.1]). NLP-based exclusion resulted in 444 patients increasing PPV to 77.9 % (95%CI [73.7, 81.7]) while sensitivity remained 96.3 % (95%CI [93.8, 98.0]). In the validation center, text-mining identified 333 patients (sensitivity 97.6 % (95%CI [91.6, 99.7]), PPV 58.2 % (95%CI [52.8, 63.6])) and NLP-based exclusion resulted in 223 patients, increasing PPV to 86.1 % (95%CI [80.9, 90.4]) with 98.0 % (95%CI [94.9, 99.4]) sensitivity. Our identification method outperformed ICD-10-coding predominantly in identifying MPO+ and organ-limited AAV patients., Conclusions: Our study highlights the advantages of implementing AI, notably NLP, to accurately identify rare AAV patients within large EHR-systems and demonstrates the applicability and transportability. Therefore, this method can reduce efforts to identify AAV patients and accelerate real-world research, while avoiding bias by ICD-10-coding., Competing Interests: Declaration of competing interest The work of YKOT is supported by the Dutch Kidney Foundation (17OKG04) and by the Arthritis Research and Collaboration Hub (ARCH) foundation. ARCH is funded by Dutch Arthritis Foundation (ReumaNederland). YKOT received an unrestricted research grant from GlaxoSmithKline, Aurinia Pharmaceuticals and Vifor Pharma. The LUMC received consulting fees from Aurinia Pharmaceuticals, Novartis, GSK, KezarBio, Vifor Pharma, Otsuka Pharmaceuticals on consultancies delivered by YKOT., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The relationship between sodium, blood pressure and extracellular volume could not be more pronounced or complex than in a dialysis patient. We review the patients' sources of sodium exposure in the form of dietary salt intake, medication administration, and the dialysis treatment itself. In addition, the roles dialysis modalities, hemodialysis types, and dialysis fluid sodium concentration have on blood pressure, intradialytic symptoms, and interdialytic weight gain affect patient outcomes are discussed. We review whether sodium restriction (reduced salt intake), alteration in dialysis fluid sodium concentration and the different dialysis types have any impact on blood pressure, intradialytic symptoms, and interdialytic weight gain., Competing Interests: JR is an employee of the Renal Research Institute, a wholly owned subsidiary of Fresenius Medical Care. JR holds stock in Fresenius Medical Care. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Lew, Asci, Rootjes, Ok, Penne, Sam, Tzamaloukas, Ing and Raimann.)

Objectives: ANCA-associated vasculitis (AAV) has been associated with increased risk of cardiovascular (CV) events. The aim was to assess traditional and disease-related CV risk determinants in a two-centre prospective cohort of AAV patients., Methods: Patients were recruited from centres in the Netherlands and Canada. A comprehensive CV risk assessment was performed at inclusion. Subjects were followed up yearly for 3-5 years until the first CV event, death or end of follow-up. Cox proportional hazards analyses were performed to relate baseline characteristics to the first CV event., Results: A total of 144 patients were included (mean age 62 years, female sex 44%, median Framingham risk score 14.3%). Insulin resistance was present in 73% of patients tested at inclusion, independent of concurrent prednisone therapy. After a median follow-up of 2.90 years, 16 patients (11%) experienced a CV event (14 non-fatal and 2 fatal). The incidence of CV events was 5.45 per 100 patient-years. Age, Framingham risk score, HbA1c level, Diabetes Mellitus (DM), and previous CV event were significantly associated with CV events. Other factors, such as sex, impaired renal function, dyslipidemia, hypertension, smoking history and microalbuminuria, or disease-specific variables, like ANCA serotype or disease activity, were not significantly related to CV events in univariable or age-adjusted cox regression analysis., Conclusions: Determinants of an increased CV risk were identified. Disease-related factors and treatments can further modify individual risk factors, such as for steroids causing chronic insulin resistance and DM. Treatment of risk factors is essential to optimize long-term outcomes in AAV patients., (Copyright © 2023 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Introduction: Excess sodium intake and consequent volume overload are major clinical problems in hemodialysis (HD) contributing to adverse outcomes. Saline used for priming and rinsing of the extracorporeal circuit is a potentially underappreciated source of intradialytic sodium gain. We aimed to examine the feasibility and clinical effects of replacing saline as the priming and rinsing fluid by a 5% dextrose solution., Materials and Methods: We enrolled non-diabetic and anuric stable HD patients. First, the extracorporeal circuit was primed and rinsed with approximately 200-250 mL of isotonic saline during 4 weeks (Phase 1), subsequently a similar volume of a 5% dextrose solution replaced the saline for another 4 weeks (Phase 2), followed by another 4 weeks of saline (Phase 3). We collected data on interdialytic weight gain (IDWG), pre- and post-dialysis blood pressure, intradialytic symptoms, and thirst., Results: Seventeen chronic HD patients (11 males, age 54.1 ± 18.7 years) completed the study. The average priming and rinsing volumes were 236.7 ± 77.5 and 245.0 ± 91.8 mL respectively. The mean IDWG did not significantly change (2.52 ± 0.88 kg in Phase 1; 2.28 ± 0.70 kg in Phase 2; and 2.51 ± 1.2 kg in Phase 3). No differences in blood pressures, intradialytic symptoms or thirst were observed., Conclusions: Replacing saline by 5% dextrose for priming and rinsing is feasible in stable HD patients and may reduce intradialytic sodium loading. A non-significant trend toward a lower IDWG was observed when 5% dextrose was used. Prospective studies with a larger sample size and longer follow-up are needed to gain further insight into the possible effects of using alternate priming and rinsing solutions lowering intradialytic sodium loading., Trial Registration: Identifier NCT01168947 (ClinicalTrials.gov).

Objectives: Patients with ANCA-associated vasculitis are at increased risk of cardiovascular events. The aim of the present study was to assess predictors of cardiovascular events in patients with granulomatosis with polyangiitis or eosinophilic granulomatosis with polyangiitis., Methods: This retrospective cohort study included patients from the Canadian Vasculitis Research Network cohort in Toronto. Characteristics at diagnosis were collected. During follow-up, non-fatal cardiovascular events were determined from the Vasculitis Damage Index; mortality and causes of death were recorded. Cox regression models were developed to determine predictors of cardiovascular events, defined as stroke or myocardial infarction., Results: A total of 336 patients were included (231 [69%] granulomatosis with polyangiitis; 105 [31%] eosinophilic granulomatosis with polyangiitis). The mean age at diagnosis was 44 (±18) years and 44% were male. The incidence rate for the combined outcome of all fatal and non-fatal events was 7.2 events per 1000 patient-years. In a multivariate model, family history of cardiovascular events and a higher Birmingham Vasculitis Activity Score at diagnosis were predictive of cardiovascular events (hazard ratio and 95% confidence interval 3.46 [1.06-11.28] and 1.09 [1.02-1.16] respectively). In a subgroup analysis there was no association between cardiovascular or disease-specific characteristics and cardiovascular events in eosinophilic granulomatosis with polyangiitis., Conclusions: In this cohort of patients with granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis, both traditional and disease-related risk factors were predictive of cardiovascular events. Further prospective studies should elucidate the impact of these and other modifiable risk factors on cardiovascular risk in ANCA-associated vasculitis., (Copyright © 2020 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)

Objective: This prospective study uses calf bioimpedance spectroscopy (cBIS) to guide the attainment of dry weight (DW cBIS ) in chronic hemodialysis (HD) patients. The primary aim of this study was to evaluate whether body composition is altered when fluid status is reduced to DW cBIS ., Methods: Target post-HD weight was gradually reduced from baseline (BL) until DW cBIS was achieved. DW cBIS was defined as the presence of both flattening of the curve of extracellular resistance and the attainment calf normalized resistivity in the normal range during the dialysis treatment. Extracellular volume (ECV), intracellular volume, and total body water (TBW) were measured using whole body BIS (Hydra 4200). Fluid overload, lean body mass, and fat mass were calculated according to a body composition model., Results: Seventy-three patients enrolled and 60 completed the study (55 ± 13 years, 49% male). Twenty-eight patients (25% diabetes) achieved DW cBIS , whereas 32 patients (47% diabetes) did not. Number of treatment measurements were 16 ± 10 and 12 ± 13 studies per patient in the DW cBIS and non-DW cBIS groups, respectively. Although significant decreases in body weight and ECV were observed, lean body mass and FM did not differ significantly in both groups from BL to the end of study. ECV, ECV/TBW, and fluid overload were higher in the non-DW cBIS than in the DW cBIS group both at BL and at the end of study. Ratios of intradialytic changes in calf normalized resistivity, ECV, and ECV/TBW to ultrafiltration volume were significantly lower in diabetic than in non-diabetic patients., Conclusions: This study shows that decreasing fluid status by gradual reduction of post-HD weight in both DW cBIS and Non-DW cBIS groups did not affect body composition significantly over a period of about 4 weeks., (Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Objectives: Several chronic inflammatory diseases are associated with cardiovascular disease, but the risk in ANCA-associated vasculitis is poorly quantified. The aim of the present study was to review the evidence for an increased cardiovascular risk, including ischaemic heart disease, cerebrovascular accidents and peripheral arterial disease, in patients with ANCA-associated vasculitis., Methods: A comprehensive systematic review was conducted in accordance with guidelines of preferred reporting items for systematic reviews and meta-analyses. The databases PubMed, Embase.com and the Cochrane Library (Wiley) were searched for original observational studies comparing vasculitis patients with at least one control group. Summary estimates were derived with a random-effects model and reported as relative risks., Results: One thousand three hundred and seventy-five studies were identified. Seven studies were included, comprising almost 14 000 ANCA-associated vasculitis patients vs general population controls in six studies and chronic kidney disease patients in one study. ANCA-associated vasculitis carried a relative risk of 1.65 (95% CI: 1.23, 2.22) for all cardiovascular events, 1.60 (95% CI: 1.39, 1.84) for ischaemic heart disease and 1.20 (95% CI: 0.98, 1.48) for cerebrovascular accidents. We did not find studies that addressed the risk for peripheral arterial disease separately. No heterogeneity was seen in the estimates., Conclusion: This meta-analysis of observational studies supports an increase in cardiovascular risk in patients with ANCA-associated vasculitis of ∼65%, similar to that found in other chronic inflammatory diseases. Hence, there is a clear need for active cardiovascular risk management in patients with ANCA-associated vasculitis., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

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: In ANCA-associated vasculitis the acute phase of the disease is often preceded by prodromal symptoms. The aim of the present study was to analyze the relation between the duration of the prodromal phase and renal damage., Methods: Patients with ANCA-associated vasculitis and renal involvement from a retrospective single-center cohort were divided into two equal groups based on the duration of the prodromal phase. The prodromal phase was defined as the time between first vasculitis related symptoms and the date of diagnosis. Clinical characteristics at diagnosis and renal items on the vasculitis damage index at 6 months were compared between the two groups. In addition, the relation between a long prodromal phase and 3-year end-stage renal disease and mortality as a composite outcome was studied., Results: A total of 72 patients were included (age 64 ± 12 years; 74% male; 96% Caucasian). At diagnosis, in patients with a prodromal phase ≤22 weeks versus >22 weeks estimated glomerular filtration rate and proteinuria did not differ significantly (35 (interquartile range 50) versus 30 (50) ml/min p = 0.84; 75% versus 87%, p = 0.21 respectively). Furthermore, Birmingham Vasculitis Activity Scores were comparable (7 (3), p = 0.71). At 6 months, a long prodromal phase was associated with proteinuria (odds ratio 5.38, 95% confidence interval (CI) 1.47-19.62), but not with an estimated glomerular filtration rate ≤ 50 ml/min (odds ratio 0.89, 95% CI 0.33-2.37) in multivariable analyses. In addition, a long prodromal phase was associated with end-stage renal disease/mortality (hazard ratio 5.22, 95% CI 1.13-24.20)., Conclusions: A long prodromal phase was associated with proteinuria and 3-year end-stage renal disease/mortality, but not with a reduced renal function at 6 months. These results underline the importance of an early diagnosis in ANCA-associated vasculitis patients in order to improve renal outcomes.

Online haemodiafiltration (HDF) is increasingly used in clinical practice as a routine intermittent dialysis modality. It is well known that renal impairment and renal replacement therapy can substantially affect the pharmacokinetic behaviour of several drugs. However, surprisingly few data are available on the need for specific dose adjustments during HDF. Due to convection, drug clearance may be increased during HDF as compared with standard haemodialysis. This may be of particular interest in patients undergoing anti-infective therapy, since under-dosing may compromise patient outcomes and promote the emergence of bacterial resistance. Drug clearance during HDF is determined by (i) dialysis characteristics, (ii) drug characteristics and (iii) patient characteristics. In this review, we will discuss these different determinants of drug clearance during HDF and advise on how to adjust the dose of antibacterial, antimycotic and antiviral agents in patients undergoing HDF. In addition, the possible added value of therapeutic drug monitoring is discussed. The review provides guidance for optimization of anti-infective dosing regimens in HDF patients.

Background: Renal involvement in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) requires prompt and aggressive immunosuppressive therapy. The aim of this study was to evaluate screening practice for renal involvement in AAV and its potential effect on renal outcomes., Methods: Between 2005 and 2015, ANCA-positive AAV patients in a teaching hospital in the Netherlands were retrospectively included. Complete screening for renal involvement was defined as: assessment of erythrocyturia, proteinuria and serum creatinine within two weeks of the diagnosis of AAV. Characteristics at presentation and at 12 months were compared between patients with and without complete screening., Results: A total of 109 AAV patients (63% male) were identified with a mean age of 62 ±; 14 years. Complete screening for renal involvement was performed in 90 of the 109 patients (83%). Patients with incomplete screening had a lower serum creatinine (86 ±; 53 vs. 190 ±; 185 μmol/l, p < 0.001) and were more often diagnosed outside the renal department (100% vs. 78%, p = 0.02). Three patients with incomplete screening had a rise in serum creatinine of ≥ 30% at 12 months. Incomplete screening was not associated with the development of end-stage renal disease. Urine analysis of patients with renal biopsy-proven AAV (n = 31) showed erythrocyturia in 58% after one sample and in 94% after three samples., Conclusion: Screening for renal involvement in AAV was suboptimal, primarily in patients who presented outside the renal department. A higher sensitivity for erythrocyturia is achieved if urine analysis is repeated. Incomplete screening may lead to renal impairment if renal involvement is not treated appropriately.

A 39-year-old woman presented with severe, uncontrolled and irreversible hypomagnesaemia, following cisplatin treatment in her childhood. Because high-dose oral magnesium supplementation therapy was insufficient and not tolerated, continuous subcutaneous magnesium supplementation was successfully instituted and continued in the outpatient setting. This case demonstrates that continuous subcutaneous magnesium supplementation is effective in maintaining magnesium levels within the normal range, is well tolerated and may provide a long-term solution for chronic hypomagnesaemia due to intractable renal losses.

Currently no validated diagnostic system for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is available. Therefore, diagnosing AAV is often challenging. We aimed to identify factors that lead to a clinical diagnosis AAV in ANCA positive patients in a teaching hospital in The Netherlands.In this study, all patients that tested positive for ANCA proteinase 3 (PR3) and/or myeloperoxidase (MPO) between 2005 and 2015 were analysed. Patients with a clinical diagnosis of AAV were compared with patients without a clinical diagnosis of AAV. Clinical symptoms and laboratory variables at presentation, including the ANCA titre, were collected for both patients with and without AAV. Clinical and laboratory variables related with AAV were investigated, using multivariable logistic regression.Two hundred thirty seven consecutive patients with a positive ANCA were included, of whom 119 were clinically diagnosed with AAV. Of the 118 ANCA positive patients without AAV, 87 patients had an alternative diagnosis, including inflammatory bowel disease (n = 24), other rheumatic diseases (n = 23), infection (n = 11), malignancy (n = 4), and other diagnoses (n = 25). In a multivariable regression model, a high ANCA titre (odds ratio [OR] 14.16, 95% confidence interval [CI] 6.93-28.94) and a high number of affected organ systems (OR 7.67, 95% CI 3.69-15.94) were associated with AAV.MPO and PR3 ANCA can be positive in a variety of diseases that mimic AAV. A higher ANCA titre and multiple affected organ systems may help to discriminate between AAV and other systemic illnesses in anti-PR3 and anti-MPO positive patients. A diagnostic scoring system incorporating these factors should be considered., Competing Interests: The authors have no conflicts of interest to disclose.

Background: Increased mortality rate in chronic hemodialysis (HD) patients is partly attributed to a chronic inflammatory state. Neutrophil-lymphocyte ratio (NLR), defined as the neutrophil count divided by lymphocyte count, is increasingly recognized as a marker of systemic inflammation, but its prognostic value in HD patients is unknown. The aim of this study was to assess NLR as a predictor of survival in this patient population., Methods: In this study incident chronic HD patients were stratified in tertiles of NLR based on measurements obtained 3 months after initiation of dialysis. Multivariable Cox regression was used to calculate the adjusted hazard ratios (HR) for NLR on all-cause survival. Subsequently, similar models were developed at years 2 and 3 to assess predictive value of NLR in prevalent patients., Results: We studied 5,782 incident HD patients (mean ± SD age 62 ± 15 years, 55% male, 43% Black, 52% diabetic). The median (interquartile, (IQR)) NLR at 3 months was 3.0 (2.1 - 4.5). NLR in the highest tertile (NLR ≥ 3.9) was a significant predictor of all-cause mortality after an adjustment for demographic and clinical covariates was performed. These results were confirmed at years 2 and 3. Moreover, NLR is superior to total white blood cell (WBC) count for prediction of all-cause mortality in incident hemodialysis patients (are under the receiver operating characteristic (ROC) curve of 0.66 vs. 0.56)., Conclusion: This study identifies NLR as a novel and robust predictor of all-cause mortality in incident and prevalent HD patients. NLR is an inexpensive and readily available marker that may help to identify HD patients who are at an increased risk of death.

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.

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 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: 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.

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.

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.

Background: Improving the health-related quality of life (HRQOL) for haemodialysis patients is a considerable challenge. The aim of the present study was to compare changes in HRQOL in haemodialysis patients with those observed in the general population over a 10-year period and explore factors that might explain possible differences., Methods: We compared 126 haemodialysis patients assessed in 1995 in the Netherlands Cooperative Study on the Adequacy of Dialysis-1 (NECOSAD-I) with 515 patients enrolled in 2006 in the ongoing Convective Transport Study (CONTRAST). Changes in HRQOL in these cohorts were compared with two representative samples from the general Dutch population, assessed in 1992 (n = 1,063) and 2001 (n = 10,600). HRQOL was measured with the SF-36 questionnaire. Differences in HRQOL were analysed with ANCOVA to adjust for demographic variables. To assess possible differences, we used multivariable regression analysis., Results: HRQOL in haemodialysis patients in 2006 [CONTRAST, mean age 63 ± 14 years (SD), 62% male] was significantly better than in 1995 (NECOSAD-I, 59 ± 16 years, 53% male) in four domains of the SF-36: bodily pain (+ 5 points, P = 0.009), vitality (+ 7, P < 0.001), role-emotional (+ 14, P < 0.001) and mental health (+ 8, P < 0.001), after adjusting for demographic variables. This increment could partly be explained by improved haemoglobin and phosphate levels. Compared to the general population, HRQOL improvement was most outspoken in two domains: bodily pain (+ 6, P = 0.01) and role-emotional (+ 8, P = 0.007)., Conclusions: This study showed an improvement of HRQOL in haemodialysis patients over an 11-year period of time, independent of global changes in the general population.

Background and Objectives: There is increasing awareness that residual renal function (RRF) has beneficial effects in hemodialysis (HD) patients. The aim of this study was to investigate the role of RRF, expressed as GFR, in phosphate and anemia management in chronic HD patients., Design, Setting, Participants, & Measurements: Baseline data of 552 consecutive patients from the Convective Transport Study (CONTRAST) were analyzed. Patients with a urinary output≥100 ml/24 h (n=295) were categorized in tertiles on the basis of degree of GFR and compared with anuric patients (i.e., urinary output<100 ml/24 h, n=274). Relations between GFR and serum phosphate and erythropoiesis-stimulating agent (ESA) index (weekly ESA dose per kg body weight divided by hematocrit) were analyzed with multivariable regression models., Results: Phosphate levels were between 3.5 and 5.5 mg/dl in 68% of patients in the upper tertile (GFR>4.13 ml/min per 1.73 m2), as compared with 46% in anuric patients despite lower prescription of phosphate-binding agents. Mean hemoglobin levels were 11.9±1.2 g/dl with no differences between the GFR categories. The ESA index was 31% lower in patients in the upper tertile as compared with anuric patients. After adjustments for patient characteristics, patients in the upper tertile had significantly lower serum phosphate levels and ESA index as compared with anuric patients., Conclusions: This study suggests a strong relation between RRF and improved phosphate and anemia control in HD patients. Efforts to preserve RRF in HD patients could improve outcomes and should be encouraged.

Low dialysate sodium concentrations have been associated with intradialytic symptoms such as muscle cramps and hypotensive episodes. High dialysate sodium concentrations lead to sodium loading, thirst and subsequent increase in interdialytic weight gain and hypertension. The optimal dialysate sodium concentration for an individual depends on the serum sodium concentration. The difference between the dialysate sodium concentration and the predialysis serum sodium concentration has been defined as the sodium gradient. In this article, the role of the sodium gradient in fluid overload, hypertension, intradialytic symptoms and clinical outcome is discussed. Absolute serum sodium levels should always be taken into account when interpreting the relation between sodium gradient and clinical outcomes. Alignment of the dialysate sodium with the serum sodium concentration may be beneficial in many patients., (Copyright © 2011 S. Karger AG, Basel.)

Chronic volume overload is highly prevalent in chronic hemodialysis patients and leads to hypertension, left ventricular hypertrophy and increased hospitalization and mortality rates. Volume overload is caused primarily by a positive sodium balance and can be improved by sodium restriction. The main sources of sodium excess are a high-sodium diet in the interdialytic period and a positive sodium balance during dialysis. Here we discuss different approaches to achieve neutral or negative sodium balance, including reducing dietary sodium intake, individualizing dialysate sodium prescription, abandonment of sodium profiling, and reducing saline infusion for treatment of intradialytic symptoms and as part of dialyzer rinsing and priming procedures. All of these approaches should be combined for a maximal reduction of volume overload.

Background and Objectives: Removal of beta2-microglobulin (beta2M) can be increased by adding convective transport to hemodialysis (HD). The aim of this study was to investigate the change in beta2M levels after 6-mo treatment with hemodiafiltration (HDF) and to evaluate the role of residual kidney function (RKF) and the amount of convective volume with this change., Design, Setting, Participants, & Measurements: Predialysis serum beta2M levels were evaluated in 230 patients with and 176 patients without RKF from the CONvective TRAnsport STudy (CONTRAST) at baseline and 6 mo after randomization for online HDF or low-flux HD. In HDF patients, potential determinants of change in beta2M were analyzed using multivariable linear regression models., Results: Mean serum beta2M levels decreased from 29.5 +/- 0.8 (+/-SEM) at baseline to 24.3 +/- 0.6 mg/L after 6 mo in HDF patients and increased from 31.9 +/- 0.9 to 34.4 +/- 1.0 mg/L in HD patients, with the difference of change between treatment groups being statistically significant (regression coefficient -7.7 mg/L, 95% confidence interval -9.5 to -5.6, P < 0.001). This difference was more pronounced in patients without RKF as compared with patients with RKF. In HDF patients, beta2M levels remained unchanged in patients with GFR >4.2 ml/min/1.73 m2. The beta2M decrease was not related to convective volume., Conclusions: This study demonstrated effective lowering of beta2M levels by HDF, especially in patients without RKF. The role of the amount of convective volume on beta2M decrease appears limited, possibly because of resistance to beta2M transfer between body compartments.