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      Brain Natriuretic Peptide and N-Terminal proBNP in Chronic Haemodialysis Patients

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          Abstract

          Background: Brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are released into circulation as a result of congestive heart failure (HF). As HF and water overload are frequent complications in haemodialysis (HD) patients, we decided to study the levels of BNP and NT-proBNP and their changes during HD. Methods: BNP and NT-proBNP levels were determined in 94 HD patients before and after a regular 4-h HD. We followed changes in these peptides during HD depending on age, sex, HF (NYHA classification and left ventricular ejection fraction [LVEF]), duration on HD, presence of hypertension, coronary artery disease, type of membrane used for HD [low-flux (LFx) or high-flux (HFx)] and body mass change during HD. Furthermore, patients´ basic medication and creatinine levels and presence of diabetes mellitus were monitored. Results: Respectively,94% and 100% of the patients had pre-dialysis concentrations of BNP and NT-proBNP above the cut-off values for HF. The marker levels correlated significantly both before and after HD (r = 0.903 and 0.888, respectively, p < 0.001). BNP levels significantly decreased (p < 0.0001), whereas NT-proBNP significantly increased (p < 0.0001) during HD on LFx membranes. HD on HFx membranes caused greater decrease of BNP (compared to LFx membranes, p < 0.001), but also a decrease of NT-proBNP (p < 0.001).We did not find any significant differences in marker levels for HF and non-HF patients (NYHA classification). However, both peptides reached higher levels in the group with LVEF ≤50% (p < 0.001 for both peptides). Body mass change during HD negatively correlated only with the change of NT-proBNP (r = –0.27, p < 0.05). In the multiple regression model, the change of both peptides during HD was significantly influenced by membrane type (p = 0.003 for BNP and p = 0.001 for NT-proBNP). NT-proBNP change during HD was further significantly influenced by LVEF (p = 0.012), sex (p = 0.002) and duration on HD (p = 0.006). Conclusions: Both BNP and NT-proBNP levels were significantly increased in HD patients prior to dialysis. The change in concentrations of both peptides during HD is influenced by membrane type. HD probably triggers increased production of both peptides and this increase is emphasized by impaired LVEF. This fact can be clinically observed only on NT-proBNP levels, because BNP levels are biased by significant removal of this protein during HD.

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          B-type natriuretic peptide and renal function in the diagnosis of heart failure: an analysis from the Breathing Not Properly Multinational Study.

          Both B-type natriuretic peptide (BNP) and renal function are prognostic indicators of survival in patients with congestive heart failure (CHF). However, relationships between BNP, renal function, and heart failure as an emergency diagnosis are unknown. The Breathing Not Properly Multinational Study was a prospectively designed diagnostic test evaluation study conducted in seven centers. Of 1,586 participants who presented with acute dyspnea, 1,452 patients (91.6%) had both BNP level and baseline estimated glomerular filtration rate (eGFR) available. Patients with an eGFR less than 15 mL/min/1.73 m2 and those on dialysis therapy were excluded. The final diagnosis was adjudicated by two independent cardiologists who were blinded to BNP results. The final diagnosis was CHF in 715 patients (49.2%). Raw and log-log transformed correlations between BNP and eGFR values were r = -0.19 and r = -0.17 for those with CHF and r = -0.20 and r = -0.31 for those without CHF (both P < 0.0001 for r not equal 0). Mean BNP levels were 561.6 pg/mL (162.3 fmol/mL), 647.5 pg/mL (187.1 fmol/mL), 745.6 pg/mL (215.5 fmol/mL), and 850.7 pg/mL (245.8 fmol/mL) for those with CHF and 85.4 pg/mL (24.7 fmol/mL), 131.7 pg/mL (38.1 fmol/mL), 297.2 pg/mL (85.9 fmol/mL), and 285.0 pg/mL (82.3 fmol/mL) for those without CHF in eGFR categories of 90 or greater, 89 to 60, 59 to 30, and less than 30 mL/min/1.73 m2, respectively. The area under the receiver operating characteristic curve and optimum cut points for BNP were 0.91 and 70.7 pg/mL (20.4 fmol/mL), 0.90 and 104.3 pg/mL (30.1 fmol/mL), 0.81 and 201.2 pg/mL (58.1 fmol/mL), and 0.86 and 225.0 pg/mL (65.0 fmol/mL) for the eGFR categories of 90 or greater, 89 to 60, 59 to 30, and less than 30 mL/min/1.73 m2, respectively. Renal function correlates weakly with BNP and influences the optimal cut point for BNP, particularly in those with an eGFR less than 60 mL/min/1.73 m2. Copyright 2003 by the National Kidney Foundation, Inc.
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            The influence of age, sex and other variables on the plasma level of N-terminal pro brain natriuretic peptide in a large sample of the general population.

            To identify potentially confounding variables for the interpretation of plasma N-terminal pro brain natriuretic peptide (NT-proBNP). Randomly selected subjects filled in a heart failure questionnaire and underwent pulse and blood pressure measurements, ECG, echocardiography, and blood sampling. Subjects were recruited from four Copenhagen general practices located in the same urban area and were examined in a Copenhagen University Hospital. 382 women and 290 men in four age groups: 50-59 years (n = 174); 60-69 years (n = 204); 70-79 years (n = 174); and > 80 years (n = 120). Associations between the plasma concentration of NT-proBNP and a range of clinical variables. In the undivided study sample, female sex (p < 0.0001), greater age (p < 0.0001), increasing dyspnoea (p = 0.0001), diabetes mellitus (p = 0.01), valvar heart disease (p = 0.002), low heart rate (p < 0.0001), left ventricular ejection fraction < or = 45% (p < 0.0001), abnormal ECG (p < 0.0001), high log10[plasma creatinine] (p = 0.0009), low log10[plasma glycosylated haemoglobin A1c] (p = 0.0004), and high log10[urine albumin] (p < 0.0001) were independently associated with a high plasma log10[plasma NT-proBNP] by multiple linear regression analysis. A single reference interval for the normal value of NT-proBNP is unlikely to suffice. There are several confounders for the interpretation of a given NT-proBNP concentration and at the very least adjustment should be made for the independent effects of age and sex.
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              B-type natriuretic peptide (BNP) and amino-terminal proBNP in patients with CKD: relationship to renal function and left ventricular hypertrophy.

              Most patients with chronic kidney disease (CKD) develop cardiovascular complications. Natriuretic peptides are novel markers that can be used to identify and monitor heart failure, but the effect of renal disease on these markers is not fully understood. The aim of the present study is to explore the relationship among circulating B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) concentrations and clinical variables in a cohort of patients with CKD. Plasma BNP and NT-proBNP concentrations and left ventricular (LV) mass index were measured in 213 predialysis patients with CKD. Plasma BNP and NT-proBNP concentrations increased with declining estimated glomerular filtration rate (GFR; P < 0.0001). Estimated GFR had an independent effect on plasma BNP (P = 0.0028) and, to a greater extent, plasma NT-proBNP (P < 0.0001) concentrations: mean BNP concentration increased by 20.6% per 10-mL/min/1.73 m2 (0.17-mL/s) reduction in estimated GFR compared with 37.7% for NT-proBNP. NT-proBNP/BNP ratio increased with CKD stage (P < 0.0001). Median plasma BNP and NT-proBNP concentrations were greater in patients with LV hypertrophy (P < 0.0001), and LV mass index had an independent effect on both BNP (P = 0.0223) and NT-proBNP (P < 0.0017). Estimated GFR and LV mass index have independent effects on both plasma BNP and NT-proBNP concentrations in patients with CKD. NT-proBNP appears to be affected more by declining kidney function, in keeping with the hypothesis that its clearance is predominantly renal. Our data have significant implications for application of these peptides as cardiac biomarkers in patients with CKD.
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                Author and article information

                Journal
                NEC
                Nephron Clin Pract
                10.1159/issn.1660-2110
                Nephron Clinical Practice
                S. Karger AG
                1660-2110
                2006
                July 2006
                26 May 2006
                : 103
                : 4
                : c162-c172
                Affiliations
                aInstitute of Clinical Biochemistry and Haematology and b1st Department of Internal Medicine, Charles University Hospital, Pilsen, Czech Republic
                Article
                92914 Nephron Clin Pract 2006;103:c162–c172
                10.1159/000092914
                16645318
                1149f01d-0a0f-42c6-b4c3-09dbcc80ea0b
                © 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.

                History
                : 26 November 2004
                : 30 December 2005
                Page count
                Figures: 6, Tables: 5, References: 37, Pages: 1
                Categories
                Original Paper

                Cardiovascular Medicine,Nephrology
                Brain natriuretic peptide,Haemodialysis,Heart failure,N-terminal proBNP

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