Murviel-lès-Montpellier, France
Murviel-lès-Montpellier, France

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Peters S.A.E.,University of Oxford | Peters S.A.E.,University Utrecht | Bots M.L.,University Utrecht | Canaud B.,Dialysis and Intensive Care Unit | And 17 more authors.
Nephrology Dialysis Transplantation | Year: 2016

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 m2 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. © 2015 The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.


Davenport A.,University College London | Peters S.A.E.,University of Oxford | Peters S.A.E.,University Utrecht | Bots M.L.,University Utrecht | And 15 more authors.
Kidney International | Year: 2016

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. © 2015 International Society of Nephrology.


PubMed | University Utrecht, Dialysis Research and Training Institute, Autonomous University of Barcelona, Ege University and 5 more.
Type: | Journal: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association | Year: 2016

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.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.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.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.


PubMed | University Utrecht, Dialysis Research and Training Institute, Autonomous University of Barcelona, Johns Hopkins University and 6 more.
Type: Comparative Study | Journal: Kidney international | Year: 2016

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.


Morena M.,Biochemistry Laboratory | Morena M.,Montpellier University | Morena M.,Dialysis Research and Training Institute | Jaussent I.,French Institute of Health and Medical Research | And 15 more authors.
Hemodialysis International | Year: 2010

This prospective observational study aimed at evaluating efficacy and biocompatibility performances of the new heparin-coated Evodial dialyzers with/without systemic heparin reduction. After a 4-week wash-out period with reference polysulfone F70S dialyzers, 6 hemodialysis patients were sequentially dialyzed with Evodial, F70S, and Evodial dialyzers using 30% heparin reduction, each period of treatment was 4 weeks. Removal rates (RR) (urea, creatinine, and β2-microglobulin), dialysis dose, and instantaneous clearances (urea and creatinine) were measured as well as inflammatory (C-reactive protein, fibrinogen, interleukin 6, tumor necrosis factor α, and monocyte chemoattractant protein-1) and oxidative stress (OS) (superoxide anion, homocysteine, and isoprostanes) parameters at the end of each study period. Patients treated with Evodial or F70S dialyzers for 4 weeks presented comparable dialysis efficacy parameters including urea and creatinine RR, dialysis dose and instantaneous clearances. By contrast, a significantly lower but reasonably good β2-microglobulin RR was achieved with Evodial dialyzers. Regarding biocompatibility, no significant difference was observed with inflammation and OS except for postdialysis monocyte chemoattractant protein-1 which significantly decreased with Evodial dialyzers. Thirty percent heparinization reduction with Evodial dialyzers did not induce any change in inflammation but led to an improvement in OS as demonstrated by a decrease in postdialysis superoxide production and predialysis homocysteine and isoprostane. This bioactive dialyzer together with heparin dose reduction represents a good trade-off between efficacy and biocompatibility performance (improvement in OS with a weak decrease in efficacy) and its use is encouraging for hemodialysis patients not only in reducing OS but also in improving patient comorbid conditions due to lesser heparin side effects. © 2010 The Authors. Hemodialysis International © 2010 International Society for Hemodialysis.


Canaud B.,Montpellier University | Canaud B.,Dialysis Research and Training Institute | Rodriguez A.,Dialysis Research and Training Institute | Chenine L.,Montpellier University | And 8 more authors.
Hemodialysis International | Year: 2010

Whole-blood viscosity is increasingly being recognized as a factor implicated in the vascular disease progression in high-risk chronic kidney disease patients. Intermittent hemodialysis and hemodiafiltration sessions, characterized by rapid volume changes and anemia correction by erythropoietin stimulating agents, are favorable conditions for enhancing whole-blood viscosity changes and consequently triggering cardiovascular events. To evaluate whole-blood viscosity changes induced by hemodiafiltration, a cross-sectional study has been performed in a group of 28 stable patients. In order to assess the impact of vessel size on whole-blood viscosity changes, we performed a dynamic whole viscosity analysis on a wide spectrum of shear rates reproducing vasculature hemorheologic conditions. Blood viscosity changes are dependent on patient characteristics, hemoglobin, and total plasma protein concentrations. Whole blood viscosity increases significantly during hemodiafiltration over the complete spectrum of shear rates. Dynamic whole-blood viscosity (WBV) increases up to 60%, predominantly at low shear rates in small arterioles and capillary beds. This observation underlines the potential pathogenic contribution of WBV increase in capillaries triggering cardiovascular events in the postdialysis period. Eight patients died from cardiovascular events. Higher WBV increase was noted in this group but did not reach statistical significance due to the insufficient power of the study. Hemorheological changes associated with WBV increase in capillary beds may contribute to aggravate silent tissue hypoxemia and precipitate cardiovascular events in chronic kidney disease patients. Prospective studies specifically designed and powered to evaluate the impact of WBV changes on cardiovascular events in dialysis patients are required. © 2010 The Authors. Hemodialysis International © 2010 International Society for Hemodialysis.


Badiou S.,Montpellier University | Boudet A.,Montpellier University | Leray-Moragues H.,Dialysis Center | Leray-Moragues H.,Dialysis Research and Training Institute | And 5 more authors.
Clinical Biochemistry | Year: 2016

Purpose of research Circulating cardiac troponin (cTn) has been identified as a risk factor for cardiovascular and overall mortality in patients undergoing hemodialysis. However, its interpretation remains difficult due to the high prevalence of patients with cTn level beyond the 99th percentile. Determining the cTn reference change value (RCV) may help in assessing a clinically significant change of cTn during regular follow-up of patients. We aimed to determine the long-term RCV of cTn in such patients and to calculate the perdialytic reduction rate of cTn. Design and methods To calculate RCV, high-sensitivity (hs)-cTnT (Roche), hs-cTnI (Abbott), and cTnI-ultra (Siemens) were determined every month before the midweek dialysis session over a 3-month period in 36 stable hemodialysis patients. cTn was also measured after the midweek dialysis session to calculate the cTn removal rate. Results The mean RCV (95% confidence interval) was 22% (18–26) for hs-cTnT versus 53% (34–73) for hs-cTnI versus 65% (45–84) for cTnI-ultra. Log-normal RCV (%) was − 19/+25 for hs-cTnT, − 33/+96 for hs-cTnI, and − 39/+115 for cTnI-ultra. The index of individuality was < 0.6 regardless of the cTn assay used. A significantly greater reduction rate was observed for hs-cTnT (48%) than for hs-cTnI (30%, p < 0.001) and cTnI-ultra (29%, p < 0.05). Conclusions These results underline the need to use the RCV approach rather than cutoff points to identify the critical change in long-term serial cTn levels. In addition, RCV should be determined for each available assay due to significant differences between assays. Removal of cTn during hemodialysis sessions should also be considered if acute coronary syndrome is suspected during a session. © 2016 The Canadian Society of Clinical Chemists


Canaud B.,Dialysis and Intensive Care Unit | Canaud B.,Dialysis Research and Training Institute | Vallee A.G.,Dialysis and Intensive Care Unit | Molinari N.,UMR 729 MISTEA | And 12 more authors.
PLoS ONE | Year: 2014

Background and Objectives: Protein-energy wasting is common in long-term haemodialysis (HD) patients with chronic kidney disease and is associated with increased morbidity and mortality. The creatinine index (CI) is a simple and useful nutritional parameter reflecting the dietary skeletal muscle protein intake and skeletal muscle mass of the patient. Because of the complexity of creatinine kinetic modeling (CKM) to derive CI, we developed a more simplified formula to estimate CI in HD patients. Design, Setting, Participants & Measurements: A large database of 549 HD patients followed over more than 20 years including monthly CKM-derived CI values was used to develop a simple equation based on patient demographics, predialysis serum creatinine values and dialysis dose (spKt/V) using mixed regression models. Results: The equation to estimate CI was developed based on age, gender, pre-dialysis serum creatinine concentrations and spKt/V urea. The equation-derived CI correlated strongly with the measured CI using CKM (correlation coefficient = 0.79, p-value <0.001). The mean error of CI prediction using the equation was 13.47%. Preliminary examples of few typical HD patients have been used to illustrate the clinical relevance and potential usefulness of CI. Conclusions: The elementary equation used to derive CI using demographic parameters, pre-dialysis serum creatinine concentrations and dialysis dose is a simple and accurate surrogate measure for muscle mass estimation. However, the predictive value of the simplified CI assessment method on mortality deserves further evaluation in large cohorts of HD patients. © 2014 Canaud et al.


PubMed | Montpellier University and Dialysis Research and Training Institute
Type: Journal Article | Journal: Clinical biochemistry | Year: 2016

Circulating cardiac troponin (cTn) has been identified as a risk factor for cardiovascular and overall mortality in patients undergoing hemodialysis. However, its interpretation remains difficult due to the high prevalence of patients with cTn level beyond the 99th percentile. Determining the cTn reference change value (RCV) may help in assessing a clinically significant change of cTn during regular follow-up of patients. We aimed to determine the long-term RCV of cTn in such patients and to calculate the perdialytic reduction rate of cTn.To calculate RCV, high-sensitivity (hs)-cTnT (Roche), hs-cTnI (Abbott), and cTnI-ultra (Siemens) were determined every month before the midweek dialysis session over a 3-month period in 36 stable hemodialysis patients. cTn was also measured after the midweek dialysis session to calculate the cTn removal rate.The mean RCV (95% confidence interval) was 22% (18-26) for hs-cTnT versus 53% (34-73) for hs-cTnI versus 65% (45-84) for cTnI-ultra. Log-normal RCV (%) was -19/+25 for hs-cTnT, -33/+96 for hs-cTnI, and -39/+115 for cTnI-ultra. The index of individuality was <0.6 regardless of the cTn assay used. A significantly greater reduction rate was observed for hs-cTnT (48%) than for hs-cTnI (30%, p<0.001) and cTnI-ultra (29%, p<0.05).These results underline the need to use the RCV approach rather than cutoff points to identify the critical change in long-term serial cTn levels. In addition, RCV should be determined for each available assay due to significant differences between assays. Removal of cTn during hemodialysis sessions should also be considered if acute coronary syndrome is suspected during a session.

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