Long-term peridialytic blood pressure changes are related to mortality.

BACKGROUND: In chronic haemodialysis (HD) patients, the relationship between long-term peridialytic blood pressure (BP) changes and mortality has not been investigated. METHODS: To evaluate whether long-term changes in peridialytic BP are related to mortality and whether treatment with HD or haemodiafiltration (HDF) differs in this respect, the combined individual participant data of three randomized controlled trials comparing HD with HDF were used. Time-varying Cox regression and joint models were applied. RESULTS: During a median follow-up of 2.94 years, 609 of 2011 patients died. As for pre-dialytic systolic BP (pre-SBP), a severe decline (≥21 mmHg) in the preceding 6 months was independently related to increased mortality [hazard ratio (HR) 1.61, P = .01] when compared with a moderate increase. Likewise, a severe decline in post-dialytic diastolic BP (DBP) was associated with increased mortality (adjusted HR 1.96, P < .0005). In contrast, joint models showed that every 5-mmHg increase in pre-SBP and post-DBP during total follow-up was related to reduced mortality (adjusted HR 0.97, P = .01 and 0.94, P = .03, respectively). No interaction was observed between BP changes and treatment modality. CONCLUSION: Severe declines in pre-SBP and post-DBP in the preceding 6 months were independently related to mortality. Therefore peridialytic BP values should be interpreted in the context of their changes and not solely as an absolute value.

Physical intradialytic patient-reported outcome measures in haemodialysis and haemodiafiltration: A cross-over study.

AIM: Standard haemodialysis (sHD) is associated with a poor survival and marked adverse intradialytic patient-reported outcome measures (ID-PROMs). Whereas physical ID-PROMs (PID-PROMs) are alleviated by cool dialysate (cHD), survival is prolonged by haemodiafiltration (HDF). So far, PID-PROMs are not prospectively compared between HD and HDF. METHODS: To assess whether PID-PROMs and thermal perception differ between sHD, cHD, low volume HDF (lvHDF) and high volume HDF (hvHDF), 40 patients were cross-over randomized to each modality for 2 weeks. Dialysate temperature (Td ) was 36.5°C, except in cHD (Td 35.5°C). Target convection volumes were 15 L in lvHDF and ≥ 23 L in hvHDF. PID-PROMs were evaluated with a modified Dialysis Symptom Index (mDSI) and thermal perception with the Visual Analogue Scale Thermal Perception (VAS-TP). Tb and room temperature were measured as well. RESULTS: Except for the item 'feeling cold' during cHD (p = .01), PID-PROMs did not differ between modalities, but varied markedly between patients (11/13 items, p < .05). Tb increased in sHD, lvHDF, and hvHDF (+0.30, 0.35, 0.38°C, respectively, all p < .0005), but remained stable in cHD (+0.04°C, p = .43). Thermal perception remained unaltered in sHD and both HDF modalities, but shifted towards cold in cHD (p = .007). CONCLUSION: (1) PID-PROMs did not differ between modalities, but varied markedly between patients. Hence, PID-PROMs are largely patient-dependent. (2) While Tb increased in sHD, lvHDF and hvHDF, thermal perception did not change. Yet, whereas Tb remained unaltered in cHD, cold perception emerged. Hence, as for bothersome cold sensations, cHD should be avoided in perceptive individuals.

Effect of various dialysis modalities on intradialytic hemodynamics, tissue injury and patient discomfort in chronic dialysis patients: design of a randomized cross-over study (HOLLANT).

BACKGROUND: From a recent meta-analysis it appeared that online post-dilution hemodiafiltration (HDF), especially with a high convection volume (HV-HDF), is associated with superior overall and cardiovascular survival, if compared to standard hemodialysis (HD). The mechanism(s) behind this effect, however, is (are) still unclear. In this respect, a lower incidence of intradialytic hypotension (IDH), and hence less tissue injury, may play a role. To address these items, the HOLLANT study was designed. METHODS: HOLLANT is a Dutch multicentre randomized controlled cross-over trial. In total, 40 prevalent dialysis patients will be included and, after a run-in phase, exposed to standard HD, HD with cooled dialysate, low-volume HDF and high-volume HDF (Dialog iQ® machine) in a randomized fashion. The primary endpoint is an intradialytic nadir in systolic blood pressure (SBP) of < 90 and < 100 mmHg for patients with predialysis SBP < 159 and ≥ 160 mmHg, respectively. The main secondary outcomes are 1) intradialytic left ventricle (LV) chamber quantification and deformation, 2) intradialytic hemodynamic profile of SBP, diastolic blood pressure (DBP), mean arterial pressure (MAP) and pulse pressure (PP), 3) organ and tissue damage, such as the release of specific cellular components, and 4) patient reported symptoms and thermal perceptions during each modality. DISCUSSION: The current trial is primarily designed to test the hypothesis that a lower incidence of intradialytic hypotension contributes to the superior survival of (HV)-HDF. A secondary objective of this investigation is the question whether changes in the intradialytic blood pressure profile correlate with organ dysfunction and tissue damage, and/or patient discomfort. TRIAL REGISTRATION: Registered Report Identifier: NCT03249532 # ( ClinicalTrials.gov ). Date of registration: 2017/08/15.

The probability of receiving a kidney transplantation in end-stage kidney disease patients who are treated with haemodiafiltration or haemodialysis: a pooled individual participant data from four randomised controlled trials.

BACKGROUND: Due to a critical shortage of available kidney grafts, most patients with Stage 5 Chronic Kidney Disease (CKD5) require bridging dialysis support. It remains unclear whether treatment by different dialysis modalities changes the selection and/or preparation of a potential transplant candidate. Therefore, we assessed whether the likelihood of receiving kidney transplant (both living or deceased kidney donors) differs between haemodialysis (HD) and online haemodiafiltration (HDF) in patients with CKD5D. METHODS: Individual participant data from four randomised controlled trials comparing online HDF with HD were used. Information on kidney transplant was obtained during follow-up. The likelihood of receiving a kidney transplant was compared between HD and HDF, and evaluated across different subgroups: age, sex, diabetes, history of cardiovascular disease, albumin, dialysis vintage, fistula, and level of convection volume standardized to body surface area. Hazard ratios (HRs), with corresponding 95% confidence intervals (95% CI), comparing the effect of online HDF versus HD on the likelihood of receiving a kidney transplant, were estimated using Cox proportional hazards models with a random effect for study. RESULTS: After a median follow-up of 2.5 years (Q1 to Q3: 1.9-3.0), 331 of the 1620 (20.4%) patients with CKD5D received a kidney transplant. This concerned 22% (n = 179) of patients who were treated with online HDF compared with 19% (n = 152) of patients who were treated with HD. No differences in the likelihood of undergoing a kidney transplant were found between the two dialysis modalities in both the crude analyse (HR: 1.07, 95% CI: 0.86-1.33) and adjusted analysis for age, sex, diabetes, cardiovascular history, albumin, and creatinine (HR: 1.15, 95%-CI: 0.92-1.44). There was no evidence for a differential effect across subgroups based on patient- and disease-characteristics nor in different categories of convection volumes. CONCLUSIONS: Treatment with HD and HDF does not affect the selection and/or preparation of CKD5D patients for kidney transplant given that the likelihood of receiving a kidney transplant does not differ between the dialysis modalities. These finding persisted across a variety of subgroups differing in patient and disease characteristics and is not affected by the level of convection volume delivered during HDF treatment sessions.

Clinical evidence on haemodiafiltration.

Haemodiafiltration (HDF) combines diffusive and convective solute removal in a single treatment session. HDF provides a greater removal of higher molecular weight uraemic retention solutes than conventional high-flux haemodialysis (HD). Recently completed randomized clinical trials suggest better patient survival with online HDF. The treatment is mainly used in Europe and Japan. This review gives a brief overview of the presently available evidence of the effects of HDF on clinical end points, it speculates on possible mechanisms of a beneficial effect of HDF as compared with standard HD and ends with some perspectives for the future.

Serum sclerostin: relation with mortality and impact of hemodiafiltration.

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.

Mortality reduction by post-dilution online-haemodiafiltration: a cause-specific analysis.

Background: From an individual participant data (IPD) meta-analysis from four randomized controlled trials comparing haemodialysis (HD) with post-dilution online-haemodiafiltration (ol-HDF), previously it appeared that HDF decreases all-cause mortality by 14% (95% confidence interval 25; 1) and fatal cardiovascular disease (CVD) by 23% (39; 3). Significant differences were not found for fatal infections and sudden death. So far, it is unclear, however, whether the reduced mortality risk of HDF is only due to a decrease in CVD events and if so, which CVD in particular is prevented, if compared with HD. Methods: The IPD base was used for the present study. Hazard ratios and 95% confidence intervals for cause-specific mortality overall and in thirds of the convection volume were calculated using the Cox proportional hazard regression models. Annualized mortality and numbers needed to treat (NNT) were calculated as well. Results: Besides 554 patients dying from CVD, fatal infections and sudden death, 215 participants died from 'other causes', such as withdrawal from treatment and malignancies. In this group, the mortality risk was comparable between HD and ol-HDF patients, both overall and in thirds of the convection volume. Subdivision of CVD mortality in fatal cardiac, non-cardiac and unclassified CVD showed that ol-HDF was only associated with a lower risk of cardiac casualties [0.64 (0.61; 0.90)]. Annual mortality rates also suggest that the reduction in CVD death is mainly due to a decrease in cardiac fatalities, including both ischaemic heart disease and congestion. Overall, 32 and 75 patients, respectively, need to be treated by high-volume HDF (HV-HDF) to prevent one all-cause and one CVD death, respectively, per year. Conclusion: The beneficial effect of ol-HDF on all-cause and CVD mortality appears to be mainly due to a reduction in fatal cardiac events, including ischaemic heart disease as well as congestion. In HV-HDF, the NNT to prevent one CVD death is 75 per year.

The importance of considering competing treatment affecting prognosis in the evaluation of therapy in trials: the example of renal transplantation in hemodialysis trials.

Background: During the follow-up in a randomized controlled trial (RCT), participants may receive additional (non-randomly allocated) treatment that affects the outcome. Typically such additional treatment is not taken into account in evaluation of the results. Two pivotal trials of the effects of hemodiafiltration (HDF) versus hemodialysis (HD) on mortality in patients with end-stage renal disease reported differing results. We set out to evaluate to what extent methods to take other treatments (i.e. renal transplantation) into account may explain the difference in findings between RCTs. This is illustrated using a clinical example of two RCTs estimating the effect of HDF versus HD on mortality. Methods: Using individual patient data from the Estudio de Supervivencia de Hemodiafiltración On-Line (ESHOL; n = 902) and The Dutch CONvective TRAnsport STudy (CONTRAST; n = 714) trials, five methods for estimating the effect of HDF versus HD on all-cause mortality were compared: intention-to-treat (ITT) analysis (i.e. not taking renal transplantation into account), per protocol exclusion (PP excl ; exclusion of patients who receive transplantation), PP cens (censoring patients at the time of transplantation), transplantation-adjusted (TA) analysis and an extension of the TA analysis (TA ext ) with additional adjustment for variables related to both the risk of receiving a transplant and the risk of an outcome (transplantation-outcome confounders). Cox proportional hazards models were applied. Results: Unadjusted ITT analysis of all-cause mortality led to differing results between CONTRAST and ESHOL: hazard ratio (HR) 0.95 (95% CI 0.75-1.20) and HR 0.76 (95% CI 0.59-0.97), respectively; difference between 5 and 24% risk reductions. Similar differences between the two trials were observed for the other unadjusted analytical methods (PP cens, PP excl , TA) The HRs of HDF versus HD treatment became more similar after adding transplantation as a time-varying covariate and including transplantation-outcome confounders: HR 0.89 (95% CI 0.69-1.13) in CONTRAST and HR 0.80 (95% CI 0.62-1.02) in ESHOL. Conclusions: The apparent differences in estimated treatment effects between two dialysis trials were to a large extent attributable to differences in applied methodology for taking renal transplantation into account in their final analyses. Our results exemplify the necessity of careful consideration of the treatment effect of interest when estimating the therapeutic effect in RCTs in which participants may receive additional treatments.

A closer look at the trajectory of physical functioning in chronic hemodialysis.

Background: in chronic hemodialysis, physical functioning (PF) is known to be poor. We set out to assess to what extent chronic dialysis patients are able to maintain a good physical condition over time and what the influence of age is on the trajectory of PF. Methods: we used data form 714 prevalent hemodialysis patients, enrolled in the CONvective TRAnsport STudy (CONTRAST). The PF subscale of the KDQOL SF-36 was assessed at baseline (n = 679) and during 2 years of follow-up (n = 298). Baseline PF score (0-100) was categorized into tertiles (good, intermediate and low). Change of PF of ≥ 5 points was considered clinically relevant. A regression model was applied to assess factors related to 'decline of PF (≥5 points)/low PF (0-33) at follow-up'. Results: during follow-up, only 15.3 % (1 out of 6) of patients succeeded in maintaining a good physical condition, the remainder deteriorated or died. Of the older patients (≥75) only 3.6% remained in a good physical condition. Factors related to decline/low PF were increasing age (odds ratio [OR] = 1.96 [95% CI: 1.03-3.72] for 65-74 years and OR = 2.38 [95%CI: 1.17-4.84] for ≥75 years compared to <65 years) and albumin (OR = 1.10 [95%CI: 1.01-1.18] per g/L decrease). Conclusion: very few hemodialysis patients maintain a good physical condition over a 2-year time span. Especially in older patients, physical performance is poor and decline is faster than in the healthy population. These findings should be taken into account when considering dialysis in older patients and more emphasis should be placed to attempts for improving physical condition.

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

Mortality 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.

Haemodiafiltration and mortality in end-stage kidney disease patients: a pooled individual participant data analysis from four randomized controlled trials.

BACKGROUND: Mortality rates remain high for haemodialysis (HD) patients and simply increasing the HD dose to remove more small solutes does not improve survival. Online haemodiafiltration (HDF) provides additional clearance of larger toxins compared with standard HD. Randomized controlled trials (RCTs) comparing HDF with conventional HD on all-cause and cause-specific mortality in end-stage kidney disease (ESKD) patients reported inconsistent results and were at high risk of bias. We conducted a pooled individual participant data analysis of RCTs to provide the most reliable evidence to date on the effects of HDF on mortality outcomes in ESKD patients. METHODS: Individual participant data were used from four trials that compared online HDF with HD and were designed to examine the effects of HDF on mortality endpoints. Bias by informative censoring of patients was resolved. Hazard ratios (HRs) and 95% confidence intervals (95% CI) comparing the effect of online HDF versus HD on all-cause and cause-specific mortality were calculated using the Cox proportional hazard regression models. The relationship between convection volume and the study outcomes was examined by delivered convection volume standardized to body surface area. RESULTS: After a median follow-up of 2.5 years (Q1-Q3: 1.9-3.0), 769 of the 2793 participants had died (292 cardiovascular deaths). Online HDF reduced the risk of all-cause mortality by 14% (95% CI: 1%; 25%) and cardiovascular mortality by 23% (95% CI: 3%; 39%). There was no evidence for a differential effect in subgroups. The largest survival benefit was for patients receiving the highest delivered convection volume [>23 L per 1.73 m(2) body surface area (BSA) per session], with a multivariable-adjusted HR of 0.78 (95% CI: 0.62; 0.98) for all-cause mortality and 0.69 (95% CI: 0.47; 1.00) for cardiovascular disease mortality. CONCLUSIONS: This pooled individual participant analysis on the effects of online HDF compared with conventional HD indicates that online HDF reduces the risk of mortality in ESKD patients. This effect holds across a variety of important clinical subgroups of patients and is most pronounced for those receiving a higher convection volume normalized to BSA.

Comparing Tests Assessing Protein-Energy Wasting: Relation With Quality of Life.

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.

Eccentric Left Ventricular Hypertrophy and Sudden Death in Patients with End-Stage Kidney Disease.

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.

Treatment Time or Convection Volume in HDF: What Drives the Reduced Mortality Risk?

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.

A Comparison of 8 Nutrition-Related Tests to Predict Mortality in Hemodialysis Patients.

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.

Online hemodiafiltration reduces systemic inflammation compared to low-flux hemodialysis.

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.

Clinical evidence on hemodiafiltration: a systematic review and a meta-analysis.

The general objective assigned to the European DIALysis (EUDIAL) Working Group by the European Renal Association ­ European Dialysis and Transplant Association (ERA-EDTA) was to enhance the quality of dialysis therapies in Europe in the broadest possible sense. Given the increasing interest in convective therapies, the Working Group has started by focusing on hemodiafiltration (HDF) therapies. A EUDIAL consensus conference was held in Paris on 13 October 2011 to discuss definitions, safety standards, clinical outcome and educational issues. Recently, the first report of the EUDIAL group was published, revisiting the definition, dose quantification, and safety of HDF. Since the meeting in Paris, new evidence has become available regarding the clinical benefits of HDF. This is the second report of the expert group in which the relation between HDF and clinical outcomes is systematically reviewed and analyzed, with emphasis on the relation between achieved convection volume and treatment effect.

Treatment policy rather than patient characteristics determines convection volume in online post-dilution hemodiafiltration.

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.

Hepcidin-25 is related to cardiovascular events in chronic haemodialysis patients.

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.

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 €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.