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      Predialysis NTproBNP Predicts Magnitude of Extracellular Volume Overload in Haemodialysis Patients

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          Abstract

          Introduction: Increased natriuretic peptides are associated with increased cardiovascular and all-cause mortality for haemodialysis (HD) patients. However, debate continues whether these biomarkers are increased by extracellular water (ECW) excess and can be used to aid clinical assessment of volume status and help determine target weight. Methods: We measured N terminal probrain natriuretic peptide (NT-proBNP) predialysis in 375 stable haemodialysis outpatients with corresponding pre and postdialysis multifrequency bioelectrical impedance assessments (MFBIA) of (ECW)/total body water (TBW). Results: Median age 64 (51-75), 63.9% male, 42.9% diabetic, 43.2% Caucasoid, 14.4% with a history of myocardial infarction, 8.4% coronary artery bypass surgery, dialysis vintage 28.2 (12.3-55.5) months. Median predialysis NT-proBNP 283 (123-989) pmol/l, and predialysis ECW/TBW ratio 0.397 ± 0.029. On multivariate analysis, predialysis log NT-proBNP was associated with predialysis systolic blood pressure (β 0.007, p = 0.000), weight (β −0.008, p = 0.001), valvular heart disease (β 0.342, p = 0.015, ECW/TBW (β 1.3, p = 0.019) and log CRP (β 0.145, p = 0.037). Dividing patients into NTproBNP quartiles, %ECW/TBW and relative ECW overhydration were significantly greater for the highest quartile vs. lowest (40.5 ± 4.1 vs. 39.0 ± 1.1, and 1.51 ± 1.24 vs. 0.61 ± 0.69 l, respectively, p < 0.001). Conclusion: In this study, predialysis NTproBNP values were associated with direct assessments of the extracellular volume excess measured by MFBIA and systolic arterial blood pressure. This suggests that predialysis NTproBNP values can potentially be used to aid clinical assessment of volume status in dialysis patients to determine target weight.

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          Most cited references29

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          Bioelectrical impedance analysis--part I: review of principles and methods.

          U KYLE (2004)
          The use of bioelectrical impedance analysis (BIA) is widespread both in healthy subjects and patients, but suffers from a lack of standardized method and quality control procedures. BIA allows the determination of the fat-free mass (FFM) and total body water (TBW) in subjects without significant fluid and electrolyte abnormalities, when using appropriate population, age or pathology-specific BIA equations and established procedures. Published BIA equations validated against a reference method in a sufficiently large number of subjects are presented and ranked according to the standard error of the estimate. The determination of changes in body cell mass (BCM), extra cellular (ECW) and intra cellular water (ICW) requires further research using a valid model that guarantees that ECW changes do not corrupt the ICW. The use of segmental-BIA, multifrequency BIA, or bioelectrical spectroscopy in altered hydration states also requires further research. ESPEN guidelines for the clinical use of BIA measurements are described in a paper to appear soon in Clinical Nutrition.
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            Impact of body mass and body composition on circulating levels of natriuretic peptides: results from the Dallas Heart Study.

            The association between higher body mass index (BMI) and lower B-type natriuretic peptide (BNP) level is thought to be mediated by expression of the natriuretic peptide clearance receptor (NPR-C) in adipose tissue. To explore this association, we tested 2 hypotheses: (1) that N-terminal (NT)-proBNP, which is not believed to bind NPR-C, would not be associated with BMI and (2) that lower BNP would be more closely associated with fat mass than with lean mass. Measurements of BNP, NT-proBNP, and body composition by direct dual energy x-ray absorptiometry (DEXA) were performed in 2707 subjects from the Dallas Heart Study. The associations between obesity and low BNP (<4 ng/L) or low NT-proBNP (lowest sex-specific quartile) were evaluated with multivariable logistic regression models stratified by sex and adjusted for age, race/ethnicity, hypertension, left ventricular mass, and end-diastolic volume. Higher BMI was independently associated with lower BNP and NT-proBNP (all P<0.001). When BMI was replaced with both DEXA-derived lean and fat mass, greater lean mass, but not fat mass, was associated with low BNP and NT-proBNP levels. In a large, population-based cohort, we confirm the previously described association between higher BMI and lower BNP and demonstrate a similar inverse association between BMI and NT-proBNP. Interestingly, both BNP and NT-proBNP are more closely associated with lean mass than with fat mass. These findings do not support the hypothesis that the lower BNP levels seen in obesity are driven by enhanced BNP clearance mediated via NPR-C.
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              Impact of obesity on plasma natriuretic peptide levels.

              The mechanisms linking obesity to hypertension have not been established, but sodium retention and excessive sympathetic tone are key contributors. The natriuretic peptides are important regulators of sodium homeostasis and neurohormonal activation, raising the possibility that obese individuals have an impaired natriuretic peptide response. We examined the relations of plasma B-type natriuretic peptide (BNP) and N-terminal proatrial natriuretic peptide (N-ANP) to body mass index in 3389 Framingham Study participants (1803 women) without heart failure. Multivariable regression analyses were performed, adjusting for clinical and echocardiographic covariates. BNP levels below the assay detection limit and N-ANP levels in the lowest sex-specific quartile were categorized as low. Multivariable-adjusted mean plasma BNP levels in lean ( or =30 kg/m2) men were 21.4, 15.5, and 12.7 pg/mL, respectively (trend P<0.0001). Corresponding values in women were 21.1, 16.3, and 13.1 pg/mL (trend P<0.001). A similar pattern was noted for plasma N-ANP. Obese individuals had higher odds of having low plasma BNP (multivariable-adjusted odds ratios: men, 2.51; 95% CI, 1.71 to 3.68; women, 1.84; 95% CI, 1.32 to 2.58) and low plasma N-ANP (odds ratios: men, 4.81; 95% CI, 2.98 to 7.76; women, 2.85; 95% CI, 2.01 to 4.04) compared with lean individuals. Diabetes also was associated with low plasma natriuretic peptide levels, and the negative effects of obesity and diabetes on natriuretic peptide levels were additive. Obese individuals have low circulating natriuretic peptide levels, which may contribute to their susceptibility to hypertension and hypertension-related disorders.
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                Author and article information

                Journal
                AJN
                Am J Nephrol
                10.1159/issn.0250-8095
                American Journal of Nephrology
                S. Karger AG
                0250-8095
                1421-9670
                2014
                October 2014
                14 October 2014
                : 40
                : 3
                : 251-257
                Affiliations
                aRenal Unit, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, bBumrungrad International Hospital, Bangkok, Thailand; cUCL Centre for Nephrology, Royal Free Hospital, University College London Medical School, London, UK
                Author notes
                *A. Davenport, UCL Centre for Nephrology, Royal Free Hospital, University College London Medical School, Rowland Hill Street, London NW3 2PF (UK), E-Mail andrewdavenport@nhs.uk
                Article
                368376 Am J Nephrol 2014;40:251-257
                10.1159/000368376
                25322897
                d70f59b5-3803-404e-ba24-063f15090629
                © 2014 S. Karger AG, Basel

                Open Access License: This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported license (CC BY-NC) ( http://www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only. 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
                : 10 August 2014
                : 07 September 2014
                Page count
                Figures: 3, Tables: 3, Pages: 7
                Categories
                Original Report: Patient-Oriented, Translational Research

                Cardiovascular Medicine,Nephrology
                NT-proBNP,Bioimpedance,Extracellular fluid volume,Haemodialysis
                Cardiovascular Medicine, Nephrology
                NT-proBNP, Bioimpedance, Extracellular fluid volume, Haemodialysis

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