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      In vivo Removal of High- and Low-Molecular-Weight Compounds in Hemodiafiltration with On-Line Regeneration of Ultrafiltrate

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          Abstract

          Background: Current methods of renal replacement therapy, combining convection and diffusion, are largely unsatisfactory in removing uremic toxins. Adsorption is a third mechanism that has been applied in extracorporeal therapy. This study evaluates the impact of hemodiafiltration with on-line regeneration of ultrafiltrate, a new two-step integrated sorbent system, on in vivo removal of a wide spectrum of solutes with different molecular weights. Methods: Pre- and post-dialysis concentrations of small, medium-size, and large molecules were determined in ten patients undergoing regular hemodiafiltration treatments with on-line regeneration of the ultrafiltrate. We also analyzed, at different times of the same dialysis session, the inlet and outlet ultrafiltrate; the latter had been regenerated by the sorbent cartridge and was used as reinfusion liquid. The mean dialysis time was 260 ± 21.2 min with a blood flow of 361 ± 33.3 ml/min and a reinjection volume of 3.6 ± 0.2 l/h. Results: Urea, creatinine and phosphate reduction ratio were respectively 69.8 ± 8.2, 61.9 ± 5.5, and 40.2 ± 17.3%. Removal of medium-size markers such as calcitonin, osteocalcin, β<sub>2</sub>-microglobulin, cystatin C, myoglobin and prolactin varied between 24 and 60%. The percentage of reduction for retinol binding protein and α<sub>1</sub>-microglobulin was negligible and we were unable to demonstrate any removal of α<sub>1</sub>-acid glycoprotein, pre-albumin, and albumin in the regenerated ultrafiltrate. Conclusion: The hemodiafiltration with on-line regeneration of ultrafiltrate is a new hemodialysis system, which allows uremic toxin removal over a wide molecular-weight spectrum.

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          Most cited references 18

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          Effects of high-flux hemodialysis on clinical outcomes: results of the HEMO study.

          Among the 1846 patients in the HEMO Study, chronic high-flux dialysis did not significantly affect the primary outcome of the all-cause mortality (ACM) rate or the main secondary composite outcomes, including the rates of first cardiac hospitalization or ACM, first infectious hospitalization or ACM, first 15% decrease in serum albumin levels or ACM, or all non-vascular access-related hospitalizations. The high-flux intervention, however, seemed to be associated with reduced risks of specific cardiac-related events. The relative risks (RR) for the high-flux arm, compared with the low-flux arm, were 0.80 [95% confidence interval (CI), 0.65 to 0.99] for cardiac death and 0.87 (95% CI, 0.76 to 1.00) for the composite of first cardiac hospitalization or cardiac death. Also, the effect of high-flux dialysis on ACM seemed to vary, depending on the duration of prior dialysis. This report presents secondary analyses to further explore the relationship between the flux intervention and the duration of dialysis with respect to various outcomes. The patients were stratified into a short-duration group and a long-duration group, on the basis of the mean duration of dialysis of 3.7 yr before randomization. In the subgroup that had been on dialysis for >3.7 yr, randomization to high-flux dialysis was associated with lower risks of ACM (RR, 0.68; 95% CI, 0.53 to 0.86; P = 0.001), the composite of first albumin level decrease or ACM (RR, 0.74; 95% CI, 0.60 to 0.91; P = 0.005), and cardiac deaths (RR, 0.63; 95% CI, 0.43 to 0.92; P = 0.016), compared with low-flux dialysis. No significant differences were observed in outcomes related to infection for either duration subgroup, however, and the trends for beneficial effects of high-flux dialysis on ACM rates were considerably weakened when the years of dialysis during the follow-up phase were combined with the prestudy years of dialysis in the analysis. For the subgroup of patients with <3.7 yr of dialysis before the study, assignment to high-flux dialysis had no significant effect on any of the examined clinical outcomes. These data suggest that high-flux dialysis might have a beneficial effect on cardiac outcomes. Because these results are derived from multiple statistical comparisons, however, they must be interpreted with caution. The subgroup results that demonstrate that patients with different durations of dialysis are affected differently by high-flux dialysis are interesting and require further study for confirmation.
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            Change from three times a week on-line hemodiafiltration to short daily on-line hemodiafiltration.

            Daily dialysis has shown excellent clinical results because a higher frequency of dialysis is more physiologic. On-line hemodiafiltration (OL-HDF) is a HDF technique that combines diffusion with high convection in which the dialysis fluid itself is used as a reinfusion solution. The aim of this study was to demonstrate the beneficial effect of the more effective dialysis schedule (daily dialysis) with the dialysis modality that offers the highest uremic toxin removal (on-line HDF). Eight patients, six males and two females, on standard 4 to 5 hours three times a week OL-HDF (S-OL-HDF) were switched to daily OL-HDF (D-OL-HDF) 2 to 21/2 hours six times per week. Dialysis parameters were identical during both periods and only frequency and dialysis time of each session were changed. Tolerance, uremic toxin removal, urea kinetics, biochemical and anemia profiles, blood pressure, and left ventricular hypertrophy were evaluated. D-OL-HDF was well accepted and tolerated. The disappearance of postdialysis fatigue was rapidly reported by patients. Patients mantained the same [time average concentration (TAC) and weekly single-pool Kt/V (spKt/V)] throughout the study. However, equivalent renal urea clearance (EKR), standard Kt/V and weekly urea reduction ratio (URR) were increased during D-OL-HDF. Weekly urea, creatinine, osteocalcin, beta2-microglobulin, myoglobin, and prolactin reduction ratios were improved with D-OL-HDF. There was a significant decrease in predialysis plasma levels of urea, creatinine, acid uric, beta2-microglobulin and homocysteine over 6 months. Phosphate binders were reduced and antihypertensive drugs were stopped. A 30% regression of left ventricular mass was observed. The change from S-OL-HDF to D-OL-HDF was well tolerated. Disappearance of postdialysis fatigue, better dialysis adequacy, a higher removal of middle and large molecules, a reduction of phosphate binders, improvement of status nutritional, and an important reduction of cardiovascular risk factors were observed.
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              NO CHANGE IN CORRECTED β2-MICROGLOBULIN CONCENTRATION AFTER CUPROPHANE HAEMODIALYSIS

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                Author and article information

                Journal
                NEC
                Nephron Clin Pract
                10.1159/issn.1660-2110
                Nephron Clinical Practice
                S. Karger AG
                1660-2110
                2006
                August 2006
                02 June 2006
                : 104
                : 1
                : c55-c60
                Affiliations
                aE.C.H.O., bLaboratoire de Biochimie spécialisée and cLaboratoire de Biochimie Générale CHRU, Nantes, France
                Article
                93671 Nephron Clin Pract 2006;104:c55–c60
                10.1159/000093671
                16741371
                © 2006 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.

                Page count
                Figures: 3, Tables: 2, References: 31, Pages: 1
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/93671
                Categories
                Original Paper

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