The cost-utility of haemodiafiltration versus haemodialysis in the Convective Transport Study

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 (sic)88 622 +/- 19 272 and (sic)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 (sic)287 679. Sensitivity analyses revealed that this amount will not fall below (sic)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

The effect of natriuretic C-type peptide and its change over time on mortality in patients on haemodialysis or haemodiafiltration

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

Intima-media thickness at the near or far wall of the common carotid artery in cardiovascular risk assessment

Aims: Current guidelines recommend measuring carotid intima-media thickness (IMT) at the far wall of the common carotid artery (CCA). We aimed to precisely quantify associations of near vs. far wall CCA-IMT with the risk for atherosclerotic cardiovascular disease (CVD, defined as coronary heart disease or stroke) and their added predictive values. Methods and results: We analysed individual records of 41 941 participants from 16 prospective studies in the Proof-ATHERO consortium {mean age 61 years [standard deviation (SD) = 11]; 53% female; 16% prior CVD}. Mean baseline values of near and far wall CCA-IMT were 0.83 (SD = 0.28) and 0.82 (SD = 0.27) mm, differed by a mean of 0.02 mm (95% limits of agreement: -0.40 to 0.43), and were moderately correlated [r = 0.44; 95% confidence interval (CI): 0.39-0.49). Over a median follow-up of 9.3 years, we recorded 10 423 CVD events. We pooled study-specific hazard ratios for CVD using random-effects meta-analysis. Near and far wall CCA-IMT values were approximately linearly associated with CVD risk. The respective hazard ratios per SD higher value were 1.18 (95% CI: 1.14-1.22; I² = 30.7%) and 1.20 (1.18-1.23; I² = 5.3%) when adjusted for age, sex, and prior CVD and 1.09 (1.07-1.12; I² = 8.4%) and 1.14 (1.12-1.16; I²=1.3%) upon multivariable adjustment (all P < 0.001). Assessing CCA-IMT at both walls provided a greater C-index improvement than assessing CCA-IMT at one wall only [+0.0046 vs. +0.0023 for near (P < 0.001), +0.0037 for far wall (P = 0.006)]. Conclusions: The associations of near and far wall CCA-IMT with incident CVD were positive, approximately linear, and similarly strong. Improvement in risk discrimination was highest when CCA-IMT was measured at both walls

Hemodiafiltration: Theory, technology and clinical practice

This book gives a complete description of online hemodiafiltration, in five sections. It is unique in the systematic and complete way in which hemodiafiltration is described. Each chapter is completed by a point-to-point summary of essential information, in a separate text box. Part of the book is dedicated to the theoretical background of convective clearance. In this part, safety issues and quality control is reviewed (especially on the quality of water for dialysis and substitution fluid), as well as equipment (both dialyzers and machines) with which this treatment can be performed. As recently the results of several randomized controlled trials were available, the effect of hemodiafiltration on hard clinical end points (mortality and morbidity) is discussed in detail. This has not been done before, as the most recent book/journal on hemodiafiltration was published in 2011, before the results of the 3 randomized controlled trials were published. Furthermore, the methodological quality of the trials is discussed by an expert, in order to help the readers in their judgment of the trials Part of the book concentrates on the effect of the treatment on several biomarkers and uremic toxins. Several clinically relevant issues is discussed separately, such as the prescription of anticoagulation during the treatment, drug prescription and clearance for patients treated with hemodiafiltration, and hemodynamic stability. Finally, a practical guide on how to perform the treatment is provided. In this unique section, seemingly simple but important details of hemodiafiltration-treatment is discussed, such as the importance of needle size for blood flow rates, the difference between filtration fraction and substitution ratio, the different targets that can be set and how to reach them. As most literature is mainly focused on theoretical issues, this unique feature really will help the field to perform hemodiafiltration, and answer practical questions

Platelet activation during haemodialysis: Comparison of cuprammonium rayon and polysulfone membranes

Background/Aim: Haemodialysis-treated patients are at a high risk of developing cardiovascular disease. Part of this risk may be attributable to the type of the dialysis membrane used. We evaluated whether different dialysis membranes differ with respect to platelet activation. Methods: In a randomized crossover trial, the platelet activation was measured in 14 patients treated with two different dialyzers (cuprammonium rayon membrane and polysulfone membrane). We compared the platelet activation over the dialyzer and between dialyzers after several weeks of dialysis. Results: There were no differences between the two dialyzers in platelet activation over the dialyzer. After 2 weeks, however, the expression of CD62P, CD63, and PAC-1 was statistically significantly lower after cuprammonium membrane treatment than after polysulfone membrane treatment (mean fluorescence intensity in arbitrary units 8.0 vs. 11.1, 2.64 vs. 4.01, and 5.61 vs. 9.74, respectively). Conclusion: Dialysis with a polysulfone membrane seems to lead to more platelet activation than dialysis with a cuprammonium membrane

Lipopolysaccharide concentrations during superflux dialysis using unfiltered bicarbonate dialysate

In the present report, the design of a new dialysate delivery system to produce low to moderately contaminated dialysate is described. In addition, the first data on bacterial counts and lipopolysaccharide (LPS) concentrations in both the dialysate and the blood during hemodialysis (HD) with superflux dialyzers are presented. In this prospective study, 37 patients were randomized into two consecutive periods of 12 weeks to HD with a high flux polysulfon (PS), a superflux PS, a superflux cellulosic tri-acetate (CTA) or a superflux CTA dialyzer with filtered dialysate (CTAf), resulting in 74 periods in which measurements were obtained. Filtered dialysate showed significantly lower bacterial counts, if compared with nonfiltered dialysate (p < 0.001). As for LPS, marked differences were not observed between filtered and nonfiltered dialysate, whereas mean plasma LPS concentrations were below the value of the dialysate at all time points (p < 0.001). Plasma LPS concentrations decreased significantly during HD with all four modalities (F 60: t0 0.032 ± 0.005, t180 0.026 ± 0.009 endotoxin units (EU)/ml, p = 0.001; F 500S, t0 0.031 ± 0.004, t180 0.027 ± 0.005 EU/ml, p = 0.001; Tricea 150G: t0 0.032 ± 0.004, t180 0.025 ± 0.005 EU/ml, p < 0.001; and Tricea 150Gf: t0 0.034 ± 0.007, t180 0.025 ± 0.006 EU/ml, p < 0.001). During HD with highly permeable dialyzers and moderately contaminated dialysate, plasma LPS concentrations decreased significantly, irrespective of the material used (PS or CTA), the flux characteristics of the devices (high flux or superflux), or the presence of a bacterial filter

Cytokine profiles during clinical high-flux dialysis: No evidence for cytokine generation by circulating monocytes

Secretion of cytokines by monocytes has been implicated in the pathogenesis of dialysis-related morbidity. Cytokine generation is presumed to take place in two steps: induction of mRNA transcription for cytokines by C5a and direct membrane contact, followed by lipopolysaccharide (LPS)- induced translation of mRNA (priming/second signal theory, Kidney Int 37: 85- 93, 1990). However, the in vitro conditions on which this theory was based differed markedly from clinical dialysis. To test this postulate for routine hemodialysis, 13 patients were studied cross-over with high-flux cuprammonium, (CU), cellulose triacetate (CTA), and polysulfon dialyzers, using standard bicarbonate dialysate, as well as CTA with filtered dialysate (fCTA). Besides leukocytes, C3a, C5a, and limulus amebocyte lysate reactivity, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL- 1RA, soluble TNF receptors, and IL-1β mRNA were assessed. Only during dialysis with CU did C5a increase significantly (561 to 8185 ng/ml, p < 0.001). Endotoxin content of standard bicarbonate was higher than filtered dialysate (median, 24.3 and <5 pg/ml respectively, P = 0.002), whereas limulus amebocyte lysate reactivity was not detected in the blood, except in the case of CU. TNF-α levels were elevated before, and remained stable during, dialysis, independent of the modality used. IL-1β, IL-6, and mRNA coding for IL-1β could not be demonstrated. IL-1RA and soluble TNF receptors (p55/p75) were markedly elevated compared with normal control subjects, but showed no differences between fCTA and CTA. To summarize, no evidence was found for production and release of cytokines by monocytes during clinical high-flux bicarbonate hemodialysis, neither with complement-activating membranes nor with unfiltered dialysate. Therefore, this study sheds some doubt on the relevance of the 'priming/second signal' theory for clinical practice. The data presented suggest that reluctance to prescribe the use of high-flux dialyzers, as advocated in many reports, may not be warranted

Optimization of the convection volume in online post-dilution haemodiafiltration: practical and technical issues

In post-dilution online haemodiafiltration (ol-HDF), a relationship has been demonstrated between the magnitude of the convection volume and survival. However, to achieve high convection volumes (>22 L per session) detailed notion of its determining factors is highly desirable. This manuscript summarizes practical problems and pitfalls that were encountered during the quest for high convection volumes. Specifically, it addresses issues such as type of vascular access, needles, blood flow rate, recirculation, filtration fraction, anticoagulation and dialysers. Finally, five of the main HDF systems in Europe are briefly described as far as HDF prescription and optimization of the convection volume is concerned

Higher convection volume exchange with online hemodiafiltration is associated with survival advantage for dialysis patients: the effect of adjustment for body size

International audienceMortality remains high for hemodialysis patients. Online hemodiafiltration (OL-HDF) removes more middle-sized uremic toxins but outcomes of individual trials comparing OL-HDF with hemodialysis have been discrepant. Secondary analyses reported higher convective volumes, easier to achieve in larger patients, and improved survival. Here we tested different methods to standardize OL-HDF convection volume on all-cause and cardiovascular mortality compared with hemodialysis. Pooled individual patient analysis of four prospective trials compared thirds of delivered convection volume with hemodialysis. Convection volumes were either not standardized or standardized to weight, body mass index, body surface area, and total body water. Data were analyzed by multivariable Cox proportional hazards modeling from 2793 patients. All-cause mortality was reduced when the convective dose was unstandardized or standardized to body surface area and total body water; hazard ratio (95% confidence intervals) of 0.65 (0.51-0.82), 0.74 (0.58-0.93), and 0.71 (0.56-0.93) for those receiving higher convective doses. Standardization by body weight or body mass index gave no significant survival advantage. Higher convection volumes were generally associated with greater survival benefit with OL-HDF, but results varied across different ways of standardization for body size. Thus, further studies should take body size into account when evaluating the impact of delivered convection volume on mortality end points