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      Extracellular resistance is sensitive to tissue sodium status; implications for bioimpedance-derived fluid volume parameters in chronic kidney disease

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          Abstract

          Multifrequency bioimpedance spectroscopy (BIS) is an established method for assessing fluid status in chronic kidney disease (CKD). However, the technique is lacking in predictive value and accuracy. BIS algorithms assume constant tissue resistivity, which may vary with changing tissue ionic sodium concentration (Na +). This may introduce significant inaccuracies to BIS outputs. To investigate this, we used 23Na magnetic resonance imaging (MRI) to measure Na + in muscle and subcutaneous tissues of 10 healthy controls (HC) and 20 patients with CKD 5 (not on dialysis). The extracellular (Re) and intracellular (Ri) resistance, tissue capacitance, extracellular (ECW) and total body water (TBW) were measured using BIS. Tissue water content was assessed using proton density-weighted MRI with fat suppression. BIS-derived volume indices were comparable in the two groups (OH: HC − 0.4 ± 0.9 L vs. CKD 0.5 ± 1.9 L, p = 0.13). However, CKD patients had higher Na + (HC 21.2 ± 3.0, CKD 25.3 ± 7.4 mmol/L; p = 0.04) and significantly lower Re (HC 693 ± 93.6, CKD 609 ± 74.3 Ohms; p = 0.01); Ri and capacitance did not vary. Na + showed a significant inverse linear relationship to Re (r s = − 0.598, p < 0.01) but not Ri. This relationship of Re (y) and Na + (x) is described through equation y = − 7.39x + 814. A 20% increase in tissue ionic Na + is likely to overestimate ECW by 1.2–2.4L. Tissue Na + concentration has a significant inverse linear relationship to Re. BIS algorithms to account for this effect could improve prediction accuracy of bioimpedance derived fluid status in CKD.

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          The online version of this article (10.1007/s40620-019-00620-3) contains supplementary material, which is available to authorized users.

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          Effect of fluid management guided by bioimpedance spectroscopy on cardiovascular parameters in hemodialysis patients: a randomized controlled trial.

          Fluid overload is the main determinant of hypertension and left ventricular hypertrophy in hemodialysis patients. However, assessment of fluid overload can be difficult in clinical practice. We investigated whether objective measurement of fluid overload with bioimpedance spectroscopy is helpful in optimizing fluid status. Prospective, randomized, and controlled study. 156 hemodialysis patients from 2 centers were randomly assigned to 2 groups. Dry weight was assessed by routine clinical practice and fluid overload was assessed by bioimpedance spectroscopy in both groups. In the intervention group (n = 78), fluid overload information was provided to treating physicians and used to adjust fluid removal during dialysis. In the control group (n = 78), fluid overload information was not provided to treating physicians and fluid removal during dialysis was adjusted according to usual clinical practice. The primary outcome was regression of left ventricular mass index during a 1-year follow-up. Improvement in blood pressure and left atrial volume were the main secondary outcomes. Changes in arterial stiffness parameters were additional outcomes. Fluid overload was assessed twice monthly in the intervention group and every 3 months in the control group before the mid- or end-week hemodialysis session. Echocardiography, 48-hour ambulatory blood pressure measurement, and pulse wave analysis were performed at baseline and 12 months. Baseline fluid overload parameters in the intervention and control groups were 1.45 ± 1.11 (SD) and 1.44 ± 1.12 L, respectively (P = 0.7). Time-averaged fluid overload values significantly decreased in the intervention group (mean difference, -0.5 ± 0.8 L), but not in the control group (mean difference, 0.1 ± 1.2 L), and the mean difference between groups was -0.5 L (95% CI, -0.8 to -0.2; P = 0.001). Left ventricular mass index regressed from 131 ± 36 to 116 ± 29 g/m(2) (P < 0.001) in the intervention group, but not in the control group (121 ± 35 to 120 ± 30 g/m(2); P = 0.9); mean difference between groups was -10.2 g/m(2) (95% CI, -19.2 to -1.17 g/m(2); P = 0.04). In addition, values for left atrial volume index, blood pressure, and arterial stiffness parameters decreased in the intervention group, but not in the control group. Ambulatory blood pressure data were not available for all patients. Assessment of fluid overload with bioimpedance spectroscopy provides better management of fluid status, leading to regression of left ventricular mass index, decrease in blood pressure, and improvement in arterial stiffness. Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
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            Glycosaminoglycan polymerization may enable osmotically inactive Na+ storage in the skin.

            Osmotically inactive skin Na(+) storage is characterized by Na(+) accumulation without water accumulation in the skin. Negatively charged glycosaminoglycans (GAGs) may be important in skin Na(+) storage. We investigated changes in skin GAG content and key enzymes of GAG chain polymerization during osmotically inactive skin Na(+) storage. Female Sprague-Dawley rats were fed a 0.1% or 8% NaCl diet for 8 wk. Skin GAG content was measured by Western blot analysis. mRNA content of key dermatan sulfate polymerization enzymes was measured by real-time PCR. The Na(+) concentration in skin was determined by dry ashing. Skin Na(+) concentration during osmotically inactive Na(+) storage was 180-190 mmol/l. Increasing skin Na(+) coincided with increasing GAG content in cartilage and skin. Dietary NaCl loading coincided with increased chondroitin synthase mRNA content in the skin, whereas xylosyl transferase, biglycan, and decorin content were unchanged. We conclude that osmotically inactive skin Na(+) storage is an active process characterized by an increased GAG content in the reservoir tissue. Inhibition or disinhibition of GAG chain polymerization may regulate osmotically inactive Na(+) storage.
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              Volume overload correlates with cardiovascular risk factors in patients with chronic kidney disease.

              Volume overload is a predictor of mortality in dialysis patients. However, the fluid status of patients with chronic kidney disease (CKD) but not yet on dialysis has not been accurately characterized. We used the Body Composition Monitor, a multifrequency bioimpedance device, to measure the level of overhydration in CKD patients, focusing on the association between overhydration and cardiovascular disease risk factors. Overhydration was the difference between the amount of extracellular water measured by the Body Composition Monitor and the amount of water predicted under healthy euvolemic conditions. Volume overload was defined as an overhydration value at and above the 90th percentile for the normal population. Of the 338 patients with stages 3-5 CKD, only 48% were euvolemic. Patients with volume overload were found to use significantly more antihypertensive medications and diuretics but had higher systolic blood pressures and an increased arterial stiffness than patients without volume overload. In a multivariate analysis, male sex, diabetes, pre-existing cardiovascular disease, systolic blood pressure, serum albumin, TNF-α, and proteinuria were independently all associated with overhydration. Thus, volume overload is strongly associated with both traditional and novel risk factors for cardiovascular disease. Bioimpedance devices may aid in clinical assessment by helping to identify a high-risk group with volume overload among stages 3-5 CKD patients.
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                Author and article information

                Contributors
                nicos.mitsides3@srft.nhs.uk
                Journal
                J Nephrol
                J. Nephrol
                Journal of Nephrology
                Springer International Publishing (Cham )
                1121-8428
                1724-6059
                18 June 2019
                18 June 2019
                2020
                : 33
                : 1
                : 119-127
                Affiliations
                [1 ]GRID grid.5379.8, ISNI 0000000121662407, Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, , The University of Manchester, Manchester Academic Health Science Centre, ; Manchester, UK
                [2 ]GRID grid.415721.4, ISNI 0000 0000 8535 2371, Nephrology Department, , Salford Royal Hospital NHS Foundation Trust, ; Stott Lane, Salford, M6 8HD UK
                [3 ]NIHR Devices for Dignity Medical Technology Co-operative, Sheffield, UK
                [4 ]GRID grid.5379.8, ISNI 0000000121662407, Quantitative Biomedical Imaging Laboratory, Faculty of Biology, Medicine and Health, , University of Manchester, Manchester Academic Health Science Centre, ; Manchester, UK
                [5 ]GRID grid.5379.8, ISNI 0000000121662407, Andrology Research Unit, Division of Gastroenterology, Endocrinology and Diabetes, School of Medicine, Faculty of Biology, Medicine and Healthy, , University of Manchester, ; Manchester, UK
                [6 ]GRID grid.7445.2, ISNI 0000 0001 2113 8111, Imperial College London, ; London, UK
                [7 ]GRID grid.498924.a, Department of Renal Medicine, , Manchester University NHS Foundation Trust, ; Manchester, UK
                [8 ]Bioxydyn Limited, Manchester, UK
                Author information
                http://orcid.org/0000-0003-4588-4738
                Article
                620
                10.1007/s40620-019-00620-3
                7007413
                31214996
                13908814-16b3-4e81-a297-c0dc264287d8
                © The Author(s) 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 1 March 2019
                : 6 June 2019
                Categories
                Original Article
                Custom metadata
                © Italian Society of Nephrology 2020

                bioimpedance,sodium,ckd
                bioimpedance, sodium, ckd

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