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Obernburg am Main, Germany

Meert N.,Ghent University | Eloot S.,Ghent University | Schepers E.,Ghent University | Lemke H.-D.,EXcorLab GmbH | And 5 more authors.
Nephrology Dialysis Transplantation | Year: 2011

Background. Innovative modifications have been introduced in several types of dialyser membranes to improve adequacy and permselectivity. Which aspects of removal are modified and how this relates to different diffusive or convective strategies has, however, been insufficiently investigated.Methods. In a prospective cross-over study, 14 chronic kidney disease (Stage 5D) patients were dialysed with a second-generation high-flux dialyser (Polynephron™) in comparison to a first-generation type (DIAPES®-HF800). Both dialysers were assessed in haemodialysis, in online pre-dilution and in post-dilution haemodiafiltration. Reduction ratio (RR, %) of small water-soluble compounds (urea and uric acid), low-molecular weight proteins (LMWPs) (β2- microglobulin, cystatin C, myoglobin and retinol-binding protein) and protein-bound solutes (hippuric acid, indole acetic acid, indoxylsulphate and p-cresylsulphate) was assessed, together with albumin losses into the dialysate.Results. Comparing the two types of membranes, the second-generation dialyser demonstrated a higher RR for LMWPs, whilst at the same time exhibiting lower albumin losses but only during post-dilution haemodiafiltration. No differences in RR were detected for both the small water-soluble and the protein-bound compounds. Comparing dialysis strategies, convection removed the same amount of solute or more as compared to diffusion.Conclusions. The second-generation membrane resulted in a higher removal of LMWPs compared to the first-generation membrane, but for the other solutes, differences were less prominent. Convection was superior in removal of a broad range of uraemic retention solutes especially with the first-generation membrane. © 2011 The Author Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Krieter D.H.,University of Wurzburg | Hackl A.,University of Wurzburg | Rodriguez A.,Montpellier University | Chenine L.,Montpellier University | And 4 more authors.
Nephrology Dialysis Transplantation | Year: 2010

Background. The accumulation of larger and protein-bound toxins is involved in the uraemic syndrome but their elimination by dialysis therapy remains difficult. In the present study, the impact of the albumin permeability of recently introduced advanced high-flux dialysis membranes on the removal of such substances was tested in haemodialysis and online post-dilution haemodiafiltration.Methods. Two types of polyethersulfone membranes only differing in albumin permeability (referred as PU- and PU+) were compared in eight patients on maintenance dialysis in a prospective cross-over manner. Treatment settings were identical for individual patients: time 229 ± 22 min; blood flow rate 378 ± 33 mLmin; dialysate flow rate 500 mLmin; substitution flow rate in haemodiafiltration 94 ± 9 mLmin. Removal of the protein-bound compounds p-cresyl sulfate (pCS) and indoxyl sulfate (IS) was determined by reduction ratios (RRs), dialytic clearances and mass in continuously collected dialysate. In addition, the elimination of the low-molecular weight (LMW) proteins beta2-microglobulin, cystatin c, myoglobin (myo), free retinol-binding protein (rbp) and albumin was measured.Results. Plasma levels of the protein-bound toxins were significantly decreased by all treatment forms. However, the decreases were comparable between dialysis membranes and between haemodialysis and haemodiafiltration. The RRs of total pCS ranged between 40.4 ± 25.3 and 47.8 ± 10.3 and of total IS between 50.4 ± 2.6 and 54.6 ± 8.7. Elimination of free protein-bound toxins as assessed by their mass in dialysate closely correlated positively with the pre-treatment plasma concentrations being r = 0.920 (P < 0.001) for total pCS and r = 0.906 (P < 0.001) for total IS, respectively. Compared to haemodialysis, much higher removal of all LMW proteins was found in haemodiafiltration. Dialysis membrane differences were only obvious in haemodialysis for the larger LMW proteins myo and rbp yielding significantly higher RRs for PU+ (myo 46 ± 9 versus 37 ± 9; rbp 18 ± 5 versus 15 ± 5; P < 0.05). Additionally, the albumin loss varied between membranes and treatment modes being undetectable with PU- in haemodialysis and highest with PU+ in haemodiafiltration (1430 ± 566 mg).Conclusions. The elimination of protein-bound compounds into dialysate is predicted by the level of pre-treatment plasma concentrations and depends particularly on diffusion. Lacking enhanced removal in online post-dilution haemodiafiltration emphasizes the minor significance of convection for the clearance of these solutes. Compared to LMW proteins, the highly protein-bound toxins pCS and IS are less effectively eliminated with all treatment forms. For a sustained decrease of pCS and IS plasma levels, alternative strategies promise to be more efficient therapy forms.

Desjardins L.,French Institute of Health and Medical Research | Desjardins L.,Amiens University Hospital | Desjardins L.,University of Picardie Jules Verne | Liabeuf S.,French Institute of Health and Medical Research | And 10 more authors.
Nephrologie et Therapeutique | Year: 2014

Background and aims: Sclerostin is a circulating inhibitor of the Wnt/b-catenin pathway and may have a role in chronic kidney disease (CKD)-mineral and bone disorder. Blood sclerostin levels are known to be elevated in patients undergoing maintenance dialysis. The aims of the present study were to evaluate sclerostin levels in patients at different CKD stages and study potential associations between sclerostin levels and (i) biochemical parameters that are disturbed in CKD, (ii) markers of vascular disease and (iii) mortality. Methods: One hundred and forty patients at CKD stages 2-5D were included in the present study. Routine clinical biochemistry tests and assays for sclerostin, protein-bound uremic toxins (indox- ylsulphate [IS] and p-cresyl sulphate [PCS]) and the toxin b2 microglobulin (b2M) were performed. Aortic and coronary calcification and arterial stiffness were assessed by multislice spiral computed tomography and pulse wave velocity measurements. The enrolled patients were prospectively monitored for mortality. Results: Sclerostin levels were found to be elevated in CKD patients (especially those on hemodialysis). Furthermore, sclerostin levels were positively correlated with inflammation markers, phosphate, fibroblast growth factor 23, IS, PCS, b2M and arterial stiffness. A multivariate linear regression analysis indicated that sclerostin levels were independently associated with IS, PCS and b2M levels. Elevated serum sclerostin appeared to be associated with mortality (independently of age and inflammation). However, this association disappeared after adjustment for a propensity score including age, phosphate, interleukin-6, CKD stage and PCS. Conclusion: Our results indicate that sclerostin levels are elevated in CKD patients and are associated with inflammation, vascular lesions, uremia and (potentially) mortality. © 2014 Association Socié té de né phrologie. Published by Elsevier Masson SAS. All rights reserved.

Barreto D.V.,French Institute of Health and Medical Research | Barreto D.V.,University of Picardie Jules Verne | Barreto F.C.,French Institute of Health and Medical Research | Barreto F.C.,University of Picardie Jules Verne | And 12 more authors.
Kidney International | Year: 2010

Chronic inflammation associated with chronic kidney disease predicts all-cause and cardiovascular mortality in hemodialysis patients. Here we sought to evaluate the association between plasma levels of the inflammatory mediator interleukin-6 (IL-6) and mortality and aortic calcification/stiffness in 125 patients at different stages (2-5D) of chronic kidney disease. Using multivariate linear regression, we found that plasma IL-6 was independently associated with C-reactive protein, albumin and the stage of chronic kidney disease, but not the aortic calcification score or pulse wave velocity. During follow-up studies (median of 829 days), 38 patients died, 22 from cardiovascular events. Plasma IL-6 significantly predicted overall and cardiovascular mortality; this association persisted after multiple adjustments or restricting the analysis to pre-dialysis patients. Moreover, IL-6 was a significantly better predictor of mortality than C-reactive protein, albumin or tumor necrosis factor-α. Hence, plasma IL-6 independently predicted overall and cardiovascular mortality in patients at different stages of chronic kidney disease; however, whether lowering plasma IL-6 will affect the outcome of chronic kidney disease will require more direct evaluation. © 2010 International Society of Nephrology.

Desjardins L.,French Institute of Health and Medical Research | Desjardins L.,Amiens University Medical Center and the Jules Verne | Liabeuf S.,French Institute of Health and Medical Research | Liabeuf S.,Amiens University Medical Center and the Jules Verne | And 10 more authors.
Osteoporosis International | Year: 2012

Summary The hormone fibroblast growth factor 23 (FGF23) is involved in mineral homeostasis but may also have a role in vascular calcification and bone mineralization. In a cohort of 142 patients with CKD stages 2-5D, plasma FGF23 was independently associated with aortic calcification but not with pulse wave velocity or bone mineral density. Introduction FGF23 is involved in mineral homeostasis but may also have a role in vascular calcification and bone mineralization. Previous studies related to FGF23 and vascular and bone outcomes have been restricted to dialysis patients. The aim of the present study was to establish whether or not plasma FGF23 is associated with aortic and coronary calcification, arterial stiffness, and bone mineral density in patients with early as well as late stages of CKD. Methods In a cohort of 142 patients with CKD stages 2-5D, we made routine biochemistry and intact FGF23 determinations, and assessed aortic and coronary calcification, bone mineral density (BMD), and arterial stiffness by multislice spiral computed tomography and automated pulse wave velocity (PWV). Results Plasma intact FGF23 levels were elevated in CKD patients; the elevation preceded that of serum phosphate in early-stage CKD. Patients with elevated FGF23 levels had higher aortic and coronary calcification scores than patients with lower FGF23 levels. Multivariate linear regression analysis indicated that only age (p<0.001) and FGF23 (p=0.008) were independently associated with aortic calcification score. Plasma FGF23 was neither associated with PWV nor with BMD. Conclusion Our data suggest that plasma FGF23 is an independent biomarker of vascular calcification in patients with various CKD stages including early stages. The association between vascular calcification and FGF23 levels appears to be independent of BMD. It remains to be seen whether this association is independent of bone turnover and bone mass. © 2012 International Osteoporosis Foundation and National Osteoporosis Foundation.

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