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      Hemodiafiltration with Endogenous Reinfusion with and without Acetate-Free Dialysis Solutions: Effect on ESA Requirement

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          Abstract

          Background: Hemofiltrate reinfusion (HFR) is a form of hemodiafiltration (HDF) in which replacement fluid is constituted by ultrafiltrate from the patient ‘regenerated’ through a cartridge containing hydrophobic styrene resin. Bicarbonate-based dialysis solutions (DS) used in routine hemodialysis and HDF contain small quantities of acetate (3–5 m M) as a stabilizing agent, one of the major causes of intradialytic hypotension. Acetate-free (AF) DS have recently been made available, substituting acetate with hydrochloric acid. The impact of AF DS during HFR on Hb levels and erythropoietic-stimulating agent (ESA) requirement in chronic dialysis patients was assessed. Patients and Methods: After obtaining informed consent, 30 uremic patients treated by standard bicarbonate dialysis (BHD, DS with acetate) were randomized to treatment in 3-month cycles: first AF HFR, followed by HFR with acetate, and again AF HFR. At the beginning and end of each period, Hb and ESA requirements were evaluated. Results: A significant increase in the Hb level was observed throughout all periods of HFR versus BHD (from 11.1 to 11.86 g/dl; p = 0.04), with a significant decrease of ESA requirements from 29,500 to 25,033 IU/month (p = 0.04). Conclusion: Regardless of the presence or absence of acetate in DS, HFR per se allows a significant lowering of ESA dosage versus BHD, while at the same time increasing Hb levels. Taking for granted the clinical impact produced, HFR seems to provide a relevant decrease in end-stage renal disease patient costs.

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          Convective and diffusive losses of vitamin C during haemodiafiltration session: a contributive factor to oxidative stress in haemodialysis patients.

          Enhanced oxidative stress in haemodialysis (HD) patients may be considered as a risk factor for accelerated atherosclerosis. Reduced antioxidant defences include impairment in enzyme activities and decreased plasma levels of hydrophilic vitamin C (vit C), and cellular levels of lipophilic vitamin E (vit E). We investigated plasma levels of vit C in 19 patients undergoing regular haemodiafiltration (HDF) (mean age 62+/-7 years) and in 1846 healthy elderly subjects (HS) (mean age 69+/-5 years). The contribution of convection and diffusion was determined using paired filtration dialysis (PFD), a modified HDF technique which physically separates convective from diffusive fluxes. Blood samples were collected before and after the HDF session; in addition at 60 min of HDF, samples were drawn from arterial lines (AL) and venous lines (VL), dialysate (D) and ultrafiltrate (UF). Blood levels of total vit C were determined using an HPLC fluorescence method. Markers of oxidative stress were also assessed in both populations as follows: levels of malondialdehyde (MDA) were determined by fluorometric assay, measurements of advanced oxidation protein products (AOPP) and glutathione peroxidase (GSH-Px) activity were performed by spectrophotometric assay, and plasma vit E content was obtained by an HPLC procedure. A significant reduction in plasma vit C level was observed in HDF patients when compared with HS (1.6+/-1.4 microg/ml in HDF vs 6.6+/-3.7 microg/ml in HS; P<0.01). The HDF session was associated with a dramatic reduction in vit C levels (1.87+/-1.57 microg/ml before HDF and 0.98+/-0.68 microg/ml after HDF); at 60 min of HDF, concentrations were as follows: AL=1.35+/-1.27 microg/ml; VL=0.37+/-0.31 microg/ml, D=0.40+/-0.34 microg/ml, UF=1.24+/-1.18 microg/ml; corresponding to a diffusive flux of 271 microg/min and a convective flux of 126 microg/min. Total loss of vit C could be assessed at 66 mg/session (8--230 mg/session). According to this loss of vit C, presence of an oxidative stress was demonstrated in HD population as shown by a significant increase in MDA (1.66+/-0.27 microM in HD vs 0.89+/-0.25 microM in HS; P<0.01) and AOPP (77.5+/-29.3 microM in HD vs 23.5+/-13.2 microM in HS; P<0.01) levels, and a decrease in GSH-Px activity (259.2+/-106.3 U/l in HD vs 661.2+/-92.2 U/l in HS; P<0.01). No change in plasma vit E between both populations (30.7+/-9.1 microM in HD vs 35.3+/-7.34 microM in HS) was observed. These results suggest that HDF with highly permeable membranes is associated with a significant loss of vit C. Diffusive transport is responsible for two-thirds whereas convective phenomenon accounts for only one-third of this loss.
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            Change from conventional haemodiafiltration to on-line haemodiafiltration.

            On-line haemodiafiltration (HDF) is a technique which combines diffusion with elevated convection and uses pyrogen-free dialysate as a replacement fluid. The purpose of this study was to evaluate the difference between conventional HDF (1-3 l/h) and on-line HDF (6-12 l/h). The study included 37 patients, 25 males and 12 females. The mean age was 56.5 +/- 13 years and duration of dialysis was 62.7 +/- 49 months. Three patients dropped out for transplantation, three patients died and three failed to complete the study period. Initially all patients were on conventional HDF with high-flux membranes over the preceding 34 +/- 32 months. Treatment was performed with blood flow (QB) 402 +/- 41 ml/min, dialysis time (Td) 187 min, dialysate flow (QD) 654 +/- 126 ml/min and replacement fluid (Qi) 4.0 +/- 2 l/session. Patients were changed to on-line HDF with the same filtre and dialysis time, QD 679 +/- 38 ml/min (NS), QB 434 +/- 68 ml/min (P < 0.05) and post-dilutional replacement fluid 22.5 +/- 4.3 l/session (P < 0.001). We compared conventional HDF with on-line HDF over a period of 1 year. Dialysis adequacy was monitored according to standard clinical and biochemical criteria. Kinetic analysis of urea and beta2-micro-globulin (beta2m) was performed monthly. Tolerance was excellent and no pyrogenic reactions were observed. Pre-dialysis sodium increased 2 mEq/l during on-line HDF. Plasma potassium, pre- and post-dialysis bicarbonate, uric acid, phosphate, calcium, iPTH, albumin, total proteins, cholesterol and triglycerides remained stable. The mean plasma beta2m reduction ratio increased from 56.1 +/- 8.7% in conventional HDF to 71.1 +/- 9.1% in on-line HDF (P < 0.001). The pre-dialysis plasma beta2m decreased from 27.4 +/- 8.1 to 24.2 +/- 6.5 mg/l (P < 0.01). Mean Kt/V (Daugirdas 2nd generation) was 1.35 +/- 0.21 in conventional HDF compared with 1.56 +/- 0.29 in on-line HDF (P < 0.01), Kt/Vr (Kt/V taking into consideration post-dialysis urea rebound) 1.12 +/- 0.17 vs 1.26 +/- 0.20 (P < 0.01), BUN time average concentration (TAC) 44.4 +/- 9 vs 40.6 +/- 10 mg/dl (P < 0.05) and protein catabolic rate (PCR) 1.13 +/- 0.22 vs 1.13 +/- 0.24 g/kg (NS). There was a significant increase in haemoglobin (10.66 +/- 1.1 vs 11.4 +/- 1.5) and haematocrit (32.2 +/- 2.9 vs 34.0 +/- 4.4%), P < 0.05, during the on-line HDF period, which allowed a decrease in the erythropoietin doses (3861 +/- 2446 vs 3232 +/- 2492 UI/week), (P < 0.05). Better blood pressure control (MAP 103.8 +/- 15 vs 97.8 +/- 11 mmHg, P < 0.01) and a lower percentage of patients requiring antihypertensive drugs were also observed. The change from conventional HDF to on-line HDF results in increased convective removal and fluid replacement (18 l/session). During on-line HDF treatment, dialysis dose was increased for both small and large molecules with a decrease in uraemic toxicity level (TAC). On-line HDF provided a better correction of anaemia with lower dosages of erythropoietin. Finally, blood pressure was easily controlled.
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              Improvement of Anemia in Hemodialysis Patients Treated by Hemodiafiltration with High-Volume On-Line-Prepared Substitution Fluid

              Background: Hemodiafiltration (HDF) is associated with a lower incidence of neuropathy, carpal tunnel syndrome, joint pain, and partial correction of anemia. HDF with on-line-prepared substitution fluid (OL HDF), as compared with conventional hemodialysis, increases the treatment tolerance and, as compared with standard HDF, avoids storage problems and allows a higher substitution volume at low cost. Methods: Thirty-two hemodialysis patients treated by OL HDF for at least 9 months were studied. Hemoglobin, hematocrit, iron metabolism, serum albumin, dialysis dose and dry body weight were determined under a settled condition with regular hemodialysis 3 months before the transfer to OL HDF. The same parameters were analyzed 3, 6 and 9 months after the beginning of the new treatment modality. Results: During OL HDF, hemoglobin values significantly increased in patients without addition of recombinant human erythropoietin (rHuEPO): baseline vs. 6 months 11 ± 1.7 vs. 12 ± 1.8 g/dl (p < 0.01); baseline vs. 9 months 11 ± 1.7 vs. 12 ± 1.6 g/dl (p < 0.05). In patients on a maintenance dose of rhuEPO, this could be significantly reduced, while the target hemoglobin levels were maintained (10.6 ± 0.9 g/dl): baseline 99.8 ± 50.4 U/kg/week, 3rd month 76.2 ± 43 U/kg/week, 6th month 64.3 ± 37 U/kg/week, and 9th month 59.4 ± 38.6 U/kg/week (p = 0.007, p = 0.0006, and p = 0.0007, respectively, vs. baseline). Iron metabolism, dialysis dose, dry body weight and serum albumin levels did not significantly change during the follow-up period. Further, a stability of the rHuEPO supplementation was observed in 14 patients followed up for 24 months. Conclusions: OL HDF influences anemia and rHuEPO dose. It allows considerable anemia correction in patients without rHuEPO treatment, while it significantly reduces rHuEPO doses in those on rHuEPO treatment as compared with standard hemodialysis. The rHuEPO costs are consequently reduced.
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                Author and article information

                Journal
                BPU
                Blood Purif
                10.1159/issn.0253-5068
                Blood Purification
                S. Karger AG
                0253-5068
                1421-9735
                2011
                June 2011
                14 January 2011
                : 31
                : 4
                : 235-242
                Affiliations
                aTerritorial Department of Nephrology and Dialysis, ASL 8, Cagliari, bScientific Affairs, Bellco Srl, Mirandola, cService of Nephrology and Dialysis, Casa di Cura Sant’Elena, Quartu Sant’Elena, dDivision of Nephrology and Dialysis, ASL 1, Sassari, eDivision of Nephrology and Dialysis, ASL 8, Cagliari, fDivision of Nephrology and Dialysis, ASL 5, Oristano, gDivision of Nephrology and Dialysis, ASL 3, Nuoro, hDivision of Nephrology and Dialysis, ASL 1, Alghero, iDivision of Nephrology and Dialysis, ASL 4, Lanusei, jService of Nephrology and Dialysis, ASL 2, Tempio Pausania, kService of Nephrology and Dialysis, ASL 3, Macomer, lDivision of Nephrology and Dialysis, ASL 1, Ozieri, and mService of Nephrology and Dialysis, ASL 3, Sorgono, Italy
                Author notes
                *Piergiorgio Bolasco, MD, Territorial Department of Nephrology and Dialysis, Via Turati 4/C, IT–09045 Quartu Sant’Elena (Italy), Tel. +39 070 609 7332, Fax +39 070 609 7340, E-Mail pg.bolasco@tin.it
                Article
                322400 Blood Purif 2011;31:235–242
                10.1159/000322400
                21242676
                f83536c5-262e-4d9c-8805-a56542cfc5eb
                © 2011 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
                : 04 June 2010
                : 27 October 2010
                Page count
                Figures: 4, Tables: 6, Pages: 8
                Categories
                Original Paper

                Cardiovascular Medicine,Nephrology
                Erythropoietic-stimulating agent,Acetate-free dialysis solutions,Hemofiltrate reinfusion,Anemia,Hemodiafiltration with endogenous reinfusion

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