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      Predictive Role of BNP and NT-proBNP in Hemodialysis Patients

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          Abstract

          Background: Cardiovascular events (CVE) are a major cause of morbidity and mortality in end-stage renal disease (ESRD) patients. These patients are often excluded from CV clinical trials, and the prognostic factors associated with CVE in patients with ESRD have not been fully explored. We investigated the role of BNP and NT-proBNP in predicting the outcome and prognostic value in hemodialysis with ESRD patients. Methods: Baseline NT-proBNP and BNP, indices of dialysis adequacy, and biochemical characteristics were assessed in 217 dialysis patients with ESRD who were followed prospectively for 2 years or until death. CVE included cardiovascular death, myocardial infarction, heart failure and stroke. Results: Using multivariable Cox regression analysis, BNP and NT-proBNP remained predictive of cardiovascular mortality (BNP: hazard ratio 1.22, 95% confidence interval (CI) 1.21–11.04, p < 0.05; NT-proBNP hazard ratio 1.86, 95% CI 1.14–9.36, p < 0.05), fatal/nonfatal CHF (BNP: 1.35, 1.33–11.78, p < 0.05; NT-proBNP: 2.25, 1.54–12.68, p < 0.001) and fatal/nonfatal MI (BNP: 0.61, 2.38–19.53, p = 0.42; NT-proBNP: 1.90, 3.28–20.17, p < 0.001). NT-proBNP had better predictive value than BNP for mortality (area under the ROC curve (AUC) 0.83 vs. 0.61; p < 0.05). Conclusion: These data showed that BNP and NT-proBNP are very sensitive and specific predictors of CVE in dialysis patients.

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          Amino-terminal pro-B-type natriuretic peptide and B-type natriuretic peptide in the general community: determinants and detection of left ventricular dysfunction.

          Denise Heublein, Richard Rodeheffer, Johannes Urban … (2006)
          This study sought to characterize factors influencing amino-terminal pro-B-type natriuretic peptide (NT-proBNP) and to evaluate the ability of NT-proBNP to detect left ventricular (LV) dysfunction in a large community sample. Secretion of BNP increases in cardiac disease, making BNP an attractive biomarker. Amino-terminal proBNP, a fragment of the BNP prohormone, is a new biomarker. We evaluated factors influencing NT-proBNP in normal patients and compared the ability of NT-proBNP and BNP to detect LV dysfunction in a large community sample. Amino-terminal pro-BNP was determined in plasma samples of a previously reported and clinically and echocardiographically characterized random sample (n = 1,869, age > or =45 years) of Olmsted County, Minnesota. In normal patients (n = 746), female gender and older age were the strongest independent predictors of higher NT-proBNP. Test characteristics for detecting an LV ejection fraction < or =40% or < or =50% were determined in the total sample with receiver operating characteristic curves. Amino-terminal pro-BNP had significantly higher areas under the curve for detecting an LV ejection fraction < or =40% or < or =50% than BNP in the total population and in several male and age subgroups, whereas areas were equivalent in female subgroups. Age- and gender-adjusted cutpoints improved test characteristics of NT-proBNP. Both assays detected patients with systolic and/or moderate to severe diastolic dysfunction to a similar degree, which was less robust than the detection of LV systolic dysfunction alone. Amino-terminal pro-BNP in normal patients is affected primarily by gender and age, which should be considered when interpreting values. Importantly, in the entire population sample NT-proBNP performed at least equivalently to BNP in detecting LV dysfunction and was superior in some subgroups in detecting LV systolic dysfunction.
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            Atrium as a source of brain natriuretic polypeptide in patients with atrial fibrillation.

            Shin-Ichi Inoue, Yo Murakami, Kazuya Sano … (2000)
            Plasma brain natriuretic polypeptide (BNP) levels have been used as biochemical markers of systolic left ventricular (LV) dysfunction. Although in vitro studies have shown the existence of BNP messenger RNA in the atria, the main production site of BNP is believed to be the ventricle. The hypothesis that the atrium could be a source of BNP was examined in patients with lone atrial fibrillation (AF), the most common type of sustained arrhythmia. We studied 16 controls and 21 patients with lone AF. Plasma samples for BNP were selectively and serially obtained from the aorta, anterior interventricular vein (AIV), and coronary sinus (CS). Atrial natriuretic polypeptide (ANP) levels were also measured to determine whether the CS samples contained significant amounts of atrial venous drainage. Of the 3 sample locations, the CS had the greatest ANP levels, confirming transcatheter sampling position accuracy. BNP levels were significantly greater in the CS than AIV in the patients with AF (279 +/- 226 v 126 +/- 97 pg/mL; P < .01). Consequently, plasma BNP levels were also greater in the patients with AF than controls (103 +/- 90 v 5 +/- 2 pg/mL; P < .001). LV ejection fraction was significantly less in patients with AF than control patients. Atrial production of BNP decreased significantly after successful DC cardioversion of AF in the 5 restudied patients (182 +/- 139 v 59 +/- 64 pg/mL; P < .05). The data suggest that AF is a condition in which BNP is produced in the atrium itself.
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              Multi-biomarker risk stratification of N-terminal pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, and cardiac troponin T and I in end-stage renal disease for all-cause death.

              J. Pearce, M Murakami, C Herzog … (2004)
              In patients with end-stage renal disease (ESRD), the ability of single and multiple biomarker monitoring to predict adverse outcomes has not been well established. This study determined the prognostic value of multiple biomarkers for all-cause death over 2 years in 399 ESRD patients. The risk of all-cause death was determined by use of multiple biomarkers based on concentrations for a reference population (normal) and cutoffs based on tertile distributions in the ESRD group. Biomarkers studied included N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hsCRP; Dade Behring and Roche assays), and cardiac troponin T (cTnT; Roche) and I (cTnI; Dade Behring and Beckman Coulter assays). Relative risks of death were estimated and survival curves computed. A total of 101 deaths occurred during 594 patient-years of follow-up. Increased NT-proBNP concentrations were not predictive of death on the basis of the normal cutoffs. However, tertile analysis of NT-proBNP was significantly predictive of death and had a ROC area under the curve equivalent to or better than any of the other biomarkers. Biomarkers independently predictive of survival were hsCRP (P <0.001, either assay), cTnT (P <0.05), and cTnI (Dade, P <0.05). Two-year mortality rates were 6% (n = 45) with normal hsCRP, cTnI, and cTnT concentrations; 19% (n = 173) with increased hsCRP or cTnT and normal cTnI; 44% (n = 160) with both hsCRP and cTnT increased and normal cTnI; 61% (n = 21) with increased cTnI (Dade) or 47% (n = 74) with increased cTnI (Beckman) regardless of hsCRP or cTnT concentrations. Defined by the normal cutoffs, increased concentrations of biomarkers were present in various proportions of the 399 patients with ESRD: NT-proBNP, 99%; hsCRP, 46% (both Roche and Dade assays); cTnT, 85%; cTnI, 19% (Beckman assay) and 5% (Dade assay). Although mechanisms likely vary for causation, increased plasma hsCRP, cTnT, and cTnI above the cutoffs for our reference (normal) population were all independently predictive of subsequent death in ESRD patients. Tertile analysis for NT-proBNP also demonstrated prognostic value.
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                Author and article information

                Journal
                Journal ID (publisher-id): NEC
                Journal ID (nlm-ta): Nephron Clin Pract
                Journal ID (doi): 10.1159/issn.1660-2110
                Title: Nephron Clinical Practice
                Publisher: S. Karger AG
                ISSN (Electronic): 1660-2110
                Publication date Subscription-year: 2008
                Publication date (Print): November 2008
                Publication date (Electronic): 29 October 2008
                Volume: 110
                Issue: 3
                Pages: c178-c184
                Affiliations
                aDivision of Nephrology, Shanghai Changzheng Hospital, Second Military Medical University, and bDepartment of Gastroenterology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
                Article
                Publisher ID: 167270 Other ID: Nephron Clin Pract 2008;110:c178
                DOI: 10.1159/000167270
                PubMed ID: 18957868
                SO-VID: 61b70629-ed2c-4b7f-b614-9c2849bb8698
                Copyright © © 2008 S. Karger AG, Basel
                License:

                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
                Date received : 29 April 2008
                Date accepted : 05 August 2008
                Page count
                Figures: 1, Tables: 6, References: 19, Pages: 1
                Categories
                Subject: Original Paper

                ScienceOpen disciplines: Cardiovascular Medicine,Nephrology
                Keywords: NT-proBNP,End-stage renal disease,Cardiovascular events,Hemodialysis,BNP
                Data availability:
                ScienceOpen disciplines: Cardiovascular Medicine, Nephrology
                Keywords: NT-proBNP, End-stage renal disease, Cardiovascular events, Hemodialysis, BNP

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