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      Hemodiafiltration: Technical and Clinical Issues

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      *
      Blood Purification
      S. Karger AG
      Convection, Online hemodiafiltration, Ultrafiltration, Predilution, Backfiltration

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          Abstract

          Hemodiafiltration (HDF) seems to represent the gold standard in the field of replacement of renal function by dialysis. High convective fluxes have been correlated with better clinical outcomes. Sometimes, however, there are technical barriers to the achievement of high blood flows adequate to perform effective convective therapies. In spite of optimized procedures, the progressive increase in transmembrane pressure (TMP), the blood viscosity due to hemoconcentration and blood path resistance sometimes becomes inevitable. We propose two possible solutions that can be operated automatically via specific software in the dialysis machine: predilution on demand and backflush on demand. Predilution on demand consists in an automatic feedback of the machine, diverting part of the filtered dialysate into a predilution mode with an infusion of 200 ml in 30 s while the ultrafiltration pump stops. This produces a sudden hemodilution with a return of the parameters to acceptable values. The performance of the filter improves, and the pressure alterations are mitigated. Backflush on demand consists in an automatic feedback of the machine triggered by the TMP control, producing a positive pressure in the dialysate compartment due to a stop of filtration and rapid infusion of at least 100 ml of ultrapure dialysate into the hollow fiber. This not only produces a significant hemodilution, but also backflushes the membrane pores detaching protein layers and improving membrane permeability. These are two examples of how technology will permit to overcome technical barriers to a widespread diffusion of HDF and adequate convective dose delivery.

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          Most cited references40

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          The uremic retention solute p-cresyl sulfate and markers of endothelial damage.

          Cardiovascular disease is highly prevalent in patients with chronic kidney disease. In hemodialysis patients, the protein-bound uremic retention solute p-cresol is independently associated with cardiovascular disease. The underlying mechanisms have not been elucidated. (1) Prospective observational study of humans and (2) in vitro study in human umbilical vein endothelial cells. Hemodialysis patients. p-Cresol and its main derivative p-cresyl sulfate. Endothelial dysfunction. We studied: (1) the relation between p-cresol and blood markers of endothelial dysfunction, including soluble P-selectin and endothelial microparticles; and (2) direct effects of p-cresol and p-cresyl sulfate on endothelial cell cultures. (1) In a cohort of 100 maintenance hemodialysis patients, free serum p-cresol concentrations (median, 11.7 micromol/L; interquartile range, 15.2) were directly associated with circulating endothelial microparticles (P = 0.007), but not with soluble P-selectin (mean, 37.7 +/- 14.4 [SD] pg/mL). Other independent determinants of the degree of circulating microparticles were greater serum phosphorus (mean, 4.8 +/- 1.5 mg/dL; P = 0.008) and serum calcium concentrations (mean, 9.3 +/- 0.8 mg/dL; P = 0.03), whereas treatment with active vitamin D (P = 0.008) and vintage (median, 25 months; P = 0.04) were inversely associated. (2) In vitro, p-cresyl sulfate induced a dose-dependent increase in the shedding of endothelial microparticles (P < 0.001) by human umbilical vein endothelial cells. Shedding was reduced, but not completely aborted, in the presence of albumin, whereas the selective Rho kinase inhibitor Y-27632 abrogated the p-cresyl sulfate-induced generation of endothelial microparticles. The relationship between p-cresyl sulfate and shedding of endothelial microparticles in vivo was not mechanistically explored. p-Cresyl sulfate induces shedding of endothelial microparticles in the absence of overt endothelial damage in vitro and is independently associated with the number of endothelial microparticles in hemodialysis patients. These findings suggest that p-cresyl sulfate alters endothelial function in hemodialysis patients.
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            On-line hemodiafiltration reduces the proinflammatory CD14+CD16+ monocyte-derived dendritic cells: A prospective, crossover study.

            It is not known whether high convective transport may have a role in modulating the chronic inflammation of hemodialysis (HD) patients. The aim of this study was to evaluate the effect of on-line hemodiafiltration (OL-HDF) on proinflammatory peripheral monocytes: Percentage of CD14+CD16+ cells and their telomere length and spontaneous or bacterial DNA-induced production of cytokines (TNF-alpha and IL-6). In a prospective, crossover study, 31 patients who were on high-flux HD (HF-HD) were evaluated. Patients underwent the following sequence of treatments (4 mo each): HF-HD (basal), OL-HDF (period 1), HF-HD (period 2), OL-HDF (period 3), and HF-HD (period 4). The dialysis characteristics were similar in the two modalities; the only difference was a higher convective transport in the OL-HDF than in the HF-HD. All patients who were on OL-HDF periods showed a significantly lower number of CD14+CD16+ cells than on HF-HD (18.5 +/- 2.3 basal versus 13.6 +/- 2.9 period 1 and 13.9 +/- 2.3 period 3; P = 0.001). By contrast, HF-HD restored the number of CD14+CD16+ cells to the basal values (19.2 +/- 2.8 and 18.6 +/- 1.4, periods 2 and 4, respectively; NS). During OL-HDF periods, the reduction of CD14+CD16+ was paralleled by a decreased number of short telomere cells. Spontaneous or bacterial DNA-induced production of cytokines (TNF-alpha and IL-6) was increased in HF-HD as compared with OL-HDF. In conclusion, these results demonstrate that as compared with HF-HD, OL-HDF markedly reduces the number of proinflammatory CD14+CD16+ cells and the production of TNF-alpha and IL-6. Future studies are needed to assess the possible therapeutic effect of convective transport on chronic inflammation that is associated with HD.
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              Short-term effects of online hemodiafiltration on phosphate control: a result from the randomized controlled Convective Transport Study (CONTRAST).

              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. Short-term analysis of a secondary outcome of an ongoing randomized controlled trial. 493 (84%) consecutive patients from 589 patients included in the Convective Transport Study (CONTRAST) by January 2009 from 26 centers in 3 countries. Online hemodiafiltration (HDF) versus continuation of low-flux HD. 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). Phosphate, use of phosphate-binding agents, and proportion of patients achieving treatment targets at baseline, 3 months, and 6 months. 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. Only predialysis serum phosphate levels were measured; phosphate clearance could therefore not be calculated. HDF may help improve phosphate control. Whether this contributes to improved clinical outcome remains to be established. Copyright 2009 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                BPU
                Blood Purif
                10.1159/issn.0253-5068
                Blood Purification
                S. Karger AG
                978-3-318-05594-8
                978-3-318-05595-5
                0253-5068
                1421-9735
                2015
                September 2015
                08 September 2015
                : 40
                : Suppl 1
                : 2-11
                Affiliations
                Department of Nephrology, Dialysis and Transplantation, International Renal Research Institute of Vicenza (IRRIV), San Bortolo Hospital, Vicenza, Italy
                Author notes
                *Claudio Ronco, MD, Department of Nephrology, Dialysis and Transplantation, International Renal Research Institute of Vicenza (IRRIV), San Bortolo Hospital, Viale Rodolfi 37, IT-36100 Vicenza (Italy), E-Mail cronco@goldnet.it
                Article
                437403 Blood Purif 2015;40(suppl 1):2-11
                10.1159/000437403
                26344507
                25217d0d-806c-4286-bf57-7a351977c77a
                © 2015 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Page count
                Figures: 5, References: 55, Pages: 10
                Categories
                Review

                Cardiovascular Medicine,Nephrology
                Ultrafiltration,Online hemodiafiltration,Convection,Backfiltration,Predilution

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