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      Association between Ultrafiltration Rate and Clinical Outcome Is Modified by Muscle Mass in Hemodialysis Patients

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          Abstract

          Background: The association between ultrafiltration rate (UFR) and mortality may be affected by the muscle mass or volume status in hemodialysis (HD) patients. However, there is an absence of data regarding this association. Methods: We performed an observational study on patients (≥18 years old) who had been on HD for at least 3 months. A body composition monitor (BCM) was used for baseline bioimpedance analysis measurement. The primary composite outcome was defined as the time to death or the first cardiovascular event. Results: The median (interquartile range) UFR, volume excess measured by the BCM, and lean tissue index (LTI) (calculated as lean tissue mass/height<sup>2</sup>) were 11.4 (8.0–15.0) mL/h/kg, 2.4 (1.4–4.1) L, and 12.5 (10.4–14.4) kg/m<sup>2</sup>, respectively. During 284 person-years of follow-up, the primary outcome occurred in 44 of the 167 patients (26%). Higher UFR was associated with an increased outcome of death or cardiovascular event; the adjusted hazard ratio (HR) was 1.044 (95% confidence interval [CI]: 1.006–1.083). This association remained consistent even after adjusting for volume excess. However, the association between UFR and the primary outcome was modified by LTI ( p<sub>interaction</sub> = 0.027); the association was significant in patients with LTI < 12.5 kg/m<sup>2</sup>, and the HR (95% CI) was 1.050 (1.001–1.102). Conclusion: Higher UFR was associated with an increased risk of a composite outcome of death or cardiovascular event regardless of volume status in HD patients. However, muscle mass may modify the association between higher UFR and increased risk of a composite outcome.

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          Fluid retention is associated with cardiovascular mortality in patients undergoing long-term hemodialysis.

          Patients with chronic kidney disease (stage 5) who undergo hemodialysis treatment have similarities to heart failure patients in that both populations retain fluid frequently and have excessively high mortality. Volume overload in heart failure is associated with worse outcomes. We hypothesized that in hemodialysis patients, greater interdialytic fluid gain is associated with poor all-cause and cardiovascular survival. We examined 2-year (July 2001 to June 2003) mortality in 34,107 hemodialysis patients across the United States who had an average weight gain of at least 0.5 kg above their end-dialysis dry weight by the time the subsequent hemodialysis treatment started. The 3-month averaged interdialytic weight gain was divided into 8 categories of 0.5-kg increments (up to > or =4.0 kg). Eighty-six percent of patients gained >1.5 kg between 2 dialysis sessions. In unadjusted analyses, higher weight gain was associated with better nutritional status (higher protein intake, serum albumin, and body mass index) and tended to be linked to greater survival. However, after multivariate adjustment for demographics (case mix) and surrogates of malnutrition-inflammation complex, higher weight-gain increments were associated with increased risk of all-cause and cardiovascular death. The hazard ratios (95% confidence intervals) of cardiovascular death for weight gain or =4.0 kg (compared with 1.5 to 2.0 kg as the reference) were 0.67 (0.58 to 0.76) and 1.25 (1.12 to 1.39), respectively. In hemodialysis patients, greater fluid retention between 2 subsequent hemodialysis treatment sessions is associated with higher risk of all-cause and cardiovascular death. The mechanisms by which fluid retention influences cardiovascular survival in hemodialysis may be similar to those in patients with heart failure and warrant further research.
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            Importance of Whole-Body Bioimpedance Spectroscopy for the Management of Fluid Balance

            Introduction: Achieving normohydration remains a non-trivial issue in haemodialysis therapy. Preventing the deleterious effects of fluid overload and dehydration is difficult to achieve. Objective and clinically applicable methods for the determination of a target representing normohydration are needed. Methods: Whole-body bioimpedance spectroscopy (50 frequencies, 5–1,000 kHz) in combination with a physiologic tissue model can provide an objective target for normohydration based on the concept of excess extracellular volume. We review the efficacy of this approach in a number of recent clinical applications. The accuracy to determine fluid volumes (e.g. extracellular water), body composition (e.g. fat mass) and fluid overload was evaluated in more than 1,000 healthy individuals and patients against available gold standard reference methods (e.g. bromide, deuterium, dual-energy X-ray absorptiometry, air displacement plethysmography, clinical assessment). Results: The comparison with gold standard methods showed excellent accordance [e.g. R 2 (total body water) = 0.88; median ± SD (total body water) = –0.17 ± 2.7 litres]. Agreement with high-quality clinical assessment of fluid status was demonstrated in several hundred patients (median ± SD = –0.23 ± 1.5 litres). The association between ultrafiltration volume and change in fluid overload was reflected well by the method (median ± SD = 0.015 ± 0.8 litres). The predictive value of fluid overload on mortality underlines forcefully the clinical relevance of the normohydration target, being secondary only to the presence of diabetes. The objective normohydration target could be achieved in prevalent haemodialysis patients leading to an improvement in hypertension and reduction of adverse events. Conclusion: Whole-body bioimpedance spectroscopy in combination with a physiologic tissue model provides for the first time an objective and relevant target for clinical dry weight assessment.
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              Transcapillary Refilling Rate and Its Determinants during Haemodialysis with Standard and High Ultrafiltration Rates

              Background: Achieving euvolaemia using ultrafiltration (UF) during haemodialysis (HD) without inducing haemodynamic instability presents a major clinical challenge. Transcapillary refill is a key factor in sustaining the circulating blood volume (BV) during UF, which is in turn predicted by the rate of refilling. However, absolute plasma refilling rate (PRR), its determinants and variability with UF rate (UFR), have not been reported in the literature. Method: We studied paired HD sessions ( n = 48) in 24 patients over 2 consecutive mid-week HD treatments. Plasma refilling was measured using real-time, minute-by-minute relative BV changes obtained from the integrated BV monitoring device during UF. A fixed bolus dilution approach at the start of HD was used to calculate absolute BV. The first control HD session was undertaken with a standard UFR required to achieve the prescribed target weight, while during the second study session, a fixed (high) UFR (1 L/h) was applied, either in the first ( n = 12 patients) or in the final hour (n = 12 patients) of the HD session. Participants’ had their hydration status measured pre- and post-HD using multifrequency bioimpedance (BIS). Blood pressure was measured at 15-min intervals and blood samples were collected at 7 intervals during HD sessions. Results: The mean PRR during a standard 4-hr HD session was 4.3 ± 2.0 mL/kg/h and varied between 2 and 6 mL/kg/h. There was a mean time delay of 22 min (range 13.3–35.0 min) for onset of plasma refilling after the application of UF irrespective of standard or high UFRs. The maximum refilling occurred during the second hour of HD (mean max PRR 6.8 mL/kg/h). UFR (beta = 0.60, p 2 = 0.49) in all HD sessions. At high UFRs, PRR exceeded 10 mL/kg/h. The total overall plasma refill contribution to UF volume was not significantly different between standard and high UF. During interventions no significant haemodynamic instability was observed in the study. Conclusion: We describe absolute transcapillary refilling rate and its profile during HD with UF. The findings provide the basis for the development of UF strategies to match varying PRRs during HD. An approach to fluid removal, which is tailored to patients’ refilling rates and capacity, provides an opportunity for more precision in the practice of UF.
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                Author and article information

                Journal
                NEF
                Nephron
                10.1159/issn.1660-8151
                Nephron
                S. Karger AG
                1660-8151
                2235-3186
                2020
                September 2020
                28 July 2020
                : 144
                : 9
                : 447-452
                Affiliations
                Division of Nephrology, Department of Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Republic of Korea
                Author notes
                *Yu-Ji Lee, Division of Nephrology, Department of Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, 158, Paryong-ro, Masanhoewon-gu, Changwon 51353 (Republic of Korea), yuji.lee@samsung.com
                Article
                509350 Nephron 2020;144:447–452
                10.1159/000509350
                32721970
                cb22a55d-ec1c-4bdd-b3f3-09e896e7d7b2
                © 2020 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
                : 19 March 2020
                : 10 June 2020
                Page count
                Figures: 1, Tables: 2, Pages: 6
                Categories
                Clinical Practice: Research Article

                Cardiovascular Medicine,Nephrology
                Outcome,Lean tissue index,Hemodialysis,Ultrafiltration rate,Volume excess

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