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      A Critical Assessment of Uremia Research

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          Abstract

          There are considerably fewer randomized controlled trials investigating hemodialysis (HD) than other fields of internal medicine, and no significant improvements have been observed over time. Only the National Cooperative Dialysis Study and the HEMO trial were based on hard endpoints such as morbidity and mortality, but neither considered on-line hemodiafiltration or super-flux membranes, which are thought to provide a number of advantages in terms of the cardiovascular condition of uremic patients. However, results of well-designed clinical trials showing that increasing convection may improve the clinical outcome of HD patients are still lacking. The need for maximizing removal of uremic toxins calls for more frequent HD sessions, but this may be affected by many organizational problems. Therefore, well-designed, long-term clinical trials are urgently needed to investigate which currently available therapeutic instruments can improve the clinical outcome of uremic patients.

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          Most cited references 25

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          Predictors and consequences of altered mineral metabolism: the Dialysis Outcomes and Practice Patterns Study.

          Altered mineral metabolism contributes to bone disease, cardiovascular disease, and other clinical problems in patients with end-stage renal disease. This study describes the recent status, significant predictors, and potential consequences of abnormal mineral metabolism in representative groups of hemodialysis facilities (N= 307) and patients (N= 17,236) participating in the Dialysis Outcomes and Practice Patterns Study (DOPPS) in the United States, Europe, and Japan from 1996 to 2001. Many patients fell out of the recommended guideline range for serum concentrations of phosphorus (8% of patients below lower target range, 52% of patients above upper target range), albumin-corrected calcium (9% below, 50% above), calcium-phosphorus product (44% above), and intact PTH (51% below, 27% above). All-cause mortality was significantly and independently associated with serum concentrations of phosphorus (RR 1.04 per 1 mg/dL, P= 0.0003), calcium (RR 1.10 per 1 mg/dL, P < 0.0001), calcium-phosphorus product (RR 1.02 per 5 mg(2)/dL(2), P= 0.0001), PTH (1.01 per 100 pg/dL, P= 0.04), and dialysate calcium (RR 1.13 per 1 mEq/L, P= 0.01). Cardiovascular mortality was significantly associated with the serum concentrations of phosphorus (RR 1.09, P < 0.0001), calcium (RR 1.14, P < 0.0001), calcium-phosphorus product (RR 1.05, P < 0.0001), and PTH (RR 1.02, P= 0.03). The adjusted rate of parathyroidectomy varied 4-fold across the DOPPS countries, and was significantly associated with baseline concentrations of phosphorus (RR 1.17, P < 0.0001), calcium (RR 1.58, P < 0.0001), calcium-phosphorus product (RR 1.11, P < 0.0001), PTH (RR 1.07, P < 0.0001), and dialysate calcium concentration (RR 0.57, P= 0.03). Overall, 52% of patients received some form of vitamin D therapy, with parenteral forms almost exclusively restricted to the United States. Vitamin D was potentially underused in up to 34% of patients with high PTH, and overused in up to 46% of patients with low PTH. Phosphorus binders (mostly calcium salts during the study period) were used by 81% of patients, with potential overuse in up to 77% patients with low serum phosphorus concentration, and potential underuse in up to 18% of patients with a high serum phosphorus concentration. This study expands our understanding of the relationship between altered mineral metabolism and outcomes and identifies several potential opportunities for improved practice in this area.
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            Anaemia in haemodialysis patients of five European countries: association with morbidity and mortality in the Dialysis Outcomes and Practice Patterns Study (DOPPS)

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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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                Author and article information

                Journal
                BPU
                Blood Purif
                10.1159/issn.0253-5068
                Blood Purification
                S. Karger AG
                978-3-8055-8052-6
                978-3-318-01301-6
                0253-5068
                1421-9735
                2006
                December 2005
                23 December 2005
                : 24
                : 1
                : 71-76
                Affiliations
                Department of Nephrology and Dialysis, A. Manzoni Hospital, Lecco, Italy
                Article
                89441 Blood Purif 2006;24:71–76
                10.1159/000089441
                16361845
                © 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
                References: 36, Pages: 6
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/89441
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