Research Article The NT-ProBNP Test in Subjects with End-Stage...

Hindawi Publishing CorporationEmergency Medicine InternationalVolume 2013 Article ID 836497 8 pageshttpdxdoiorg1011552013836497

Research ArticleThe NT-ProBNP Test in Subjects with End-Stage Renal Diseaseon Hemodialysis Presenting with Acute Dyspnea Is KnowingWorth the Cost

Shaffer R S Mok1 Jose Avila2 Barry Milcarek2 and Richard Kasama2

1 Division of Internal Medicine Department of Medicine Cooper University Hospital 1 Cooper Plaza 401 Haddon Avenue3rd Floor Camden NJ 08103 USA

2Division of Nephrology Department of Internal Medicine Cooper University Hospital 1 Cooper Plaza 401 Haddon Avenue3rd Floor Camden NJ 08103 USA

Correspondence should be addressed to Shaffer R S Mok mok-shaffercooperhealthedu

Received 13 October 2012 Revised 14 January 2013 Accepted 15 January 2013

Academic Editor Rade B Vukmir

Copyright copy 2013 Shaffer R S Mok et al This is an open access article distributed under the Creative Commons AttributionLicense which permits unrestricted use distribution and reproduction in any medium provided the original work is properlycited

Background The NT-ProBNPBNP test has been validated as a marker for determining the etiology of acute dyspnea In the settingof end-stage renal disease on hemodialysis (ESRD on HD) the utility of the NT-ProBNPBNP test has not been validated Thisstudy examines the clinical utility of the NT-ProBNP test in the setting of ESRD on HD patients presenting with acute dyspneaMethods A retrospective case series of 250 subjects were admitted to Cooper University Hospital 072010-032011 with ESRD andHD presenting with dyspnea The incidences of echocardiography cardiology consultation and NT-ProBNP elevated and normalwere examined Correlation coefficients were calculated for NT-ProBNP with age (years) estimated dry weight (kg) amount offluid removed (L) and ejection fraction (EF in ) among other echocardiography parameters Results Of the total sample 235patients had NT-ProBNP levels performed Cardiology consults were placed in 688 and 58 who underwent echocardiographyOf those for whom an echocardiography was performed estimated mean EFs of 546 508 and 617 were observed amongthe NT-ProBNP elevated group normal group and no NT-ProBNP group respectively No differences were detected in all otherechocardiographymeasurements No correlationwas observed betweenNT-ProBNP and age (119903 = 005) baseline EDW(119903 = minus009)amount of fluid removed (119903 = 007) or EF (119903 = 002) Conclusion In the setting of ESRD on HD the NT-ProBNP test has noclinical utility in determining the etiology of acute dyspneaThis can be demonstrated through echocardiographic and therapeuticparameters measured in this study

1 Introduction

Both N-Terminus Pro Brain Natriuretic Peptide (NT-ProBNP) and Brain Natriuretic Peptide (BNP) hormoneshave been used in patients presenting with a chief com-plaint of dyspnea to predict whether Left Ventricular Sys-tolic Dysfunction (LVSD) is causative for this symptomThe breathing not properly data and studies by Morrisonet al demonstrated a high positive predictive value (PPV) forpredicting congestive heart failure as the etiology of patientspresenting with dyspnea to the emergency department[1ndash5]The sensitivity and specificity of the BNP assay has beenreported to be high if serum concentrations are greater than

100 picograms per milliliter (pgmL) for BNP and 500 pgmLfor NT-ProBNP for predicting LVSD as the etiology ofdyspnea [6 7]Thus with a high pretest probability membersof the emergency department utilize the NT-ProBNP andBNP in the decision tree to treat patients presenting withdyspnea The presence of chronic kidney disease (CKD) hasbeen recognized to alter their predictive value and severalauthors have suggested higher cut-off points for variousdegrees of renal impairment [8ndash16]

We could not identify any literature that validates theuse of NT-pro BNP in patients with acute onset of dyspneaand advanced CKD or end-stage renal disease (ESRD) Ourstudy retrospectively reviewed the charts of 250 consecutive

2 Emergency Medicine International

Table 1 Sample population demographics

NT-ProBNP No NT-ProBNP Total (119899 = 250)NT-ProBNP elevated NT-ProBNP normal

Mean age1 583 518 466 577Sex

Males 108 2 2 112Females 127 2 9 138

RaceBlack 98 1 3 102White 65 0 6 71Hispanic 71 3 2 76Asian 1 0 0 1Other 0 0 0 0

1Units = years

admissions where and ESRD patient presented with dyspneaWe conclude that this diagnostic purpose NT-ProBNP playsno role in the management of hemodialysis patients

2 Materials and Methods

21 Study Design This study was approved by the CooperUniversity Hospital Institutional Review Board and was incompliance with the regulations set forth by the Declarationof Helsinki It was designed as a retrospective case seriesof 250 subjects with medical record abstraction beginningfrom March 31 2011 and working backward in time to July2010 Eligible patients 18 years or older were admitted toCooper University Hospital with the diagnosis code of ICD-9= 5856 or end-stage renal disease on hemodialysis (ESRD onHD) presenting with acute symptoms of dyspnea shortnessof breath or respiratory distress This excluded patientswithout end-stage renal failure and subjects not on HD Wealso excluded subjects who presented with complaints otherthan shortness of breath chronic respiratory complaintssubjects under 18 and undergoing peritoneal dialysis or acutehemodialysis

The sample was described in terms of age (years) sexrace weight prior to dialysis and estimated dry weight(kg) creatinine (mgdL) NT-ProBNP (pgmL) hemodialysiswas within 24 hours of admission (yesno) and volumeremoved (L) cardiology consultation placed (yn) echocar-diogram performed (yn) and estimated ejection fraction() furosemide administration (yn) infectious disease con-sultation placed (yn) and administration of antibiotics (yn)

For purposes of analysis patients were categorized intoone of three groups NT-ProBNP elevated (elevated test forage) NT-ProBNP normal (test within normal range for age)or noNT-ProBNP (test not performed) NT-ProBNPpatientswere further categorized as either normal ejection fraction(EF ge 45) or low ejection fraction (lt45)

22 Study Measurements Patient subgroups were tested forsignificant differences on NT-ProBNP creatinine weight(pre-post-HD) and volume fluid removed during HDWeight was calculated by standardized measurements on

scales ldquozeroedrdquo daily by hospitals quality control staff Vol-ume removed was extrapolated from the medical record bynephrology attending physician using notes on the actualamount of postdialysis fluid removed from the patientSerum creatinine was measured by spot venous 5 samplingcentrifugation storage at minus20 degrees Celsius and thenanalyzed via Isotope Dilution Mass Spectrometry (IDMS) orstandard measurements NT-ProBNP samples were collectedby similar means as the creatinine and measured by electro-chemiluminescence immunoassay Again both laboratory-testing devices are ldquozeroedrdquo daily by laboratory staff

Cardiology staff estimated ejection fraction primar-ily by transthoracic echocardiography (TTE) M-modetwo-dimensional imaging and spectralcolor flow Dopplerrecording were obtained Measurement we performed usingshort-axis parasternal long axis and apical 2 and 4 chamberviews Measurements were performed by guidelines set forthby the American Society of Echocardiography using theQuinones formula for the parasternal long-axis Simpsonmethod in the 2 and 4 chamber views [17 18] Parametersgathered included Left Ventricular Ejection Fraction (LVEF)Right Ventricular Ejection Fraction (RVEF) quantification ofmitral regurgitation quantification of tricuspid regurgitationestimated systolic pulmonary artery pressure left atrial vol-ume left ventricular mass and EE1015840

23 Statistical Analysis Differences between subgroups andcategorical variables were tested for significance by PearsonX2 or Fishers exact test Mean differences between subgroupswere tested for significance by independent samples t-testsOverall or group specific standard deviations were useddepending on Levenersquos test for homogeneity of variancesAssociations between continuous measures were calculatedusing the Pearson correlation coefficient with effect sizedefined as the coefficient of determination

3 Results

31 Subgroup Analysis As seen in Table 1 the study popula-tion did not differ in age sex or weight When further exam-ining the study population disbursement Figure 1 shows that

Emergency Medicine International 3

250 hemodialysis patients with dyspnea presenting to Cooper University Hospital July 2010

to March 2011

11 patients did not have the NT- ProBNP test performed

6 patients with 5 patients with

239 patients had NT-ProBNP performed (Incidence 94)


5 patients with NT-

4 patients with 1 patient with

EF ge45 EF lt45

EF ge45 EF lt45 EF ge45 EF lt45

234 patients with NT-ProBNPge500 pgmL ProBNP lt500 pgmL

Figure 1 Subject selection of general population

956 of patients had aNT-ProBNP test performed of whom979 were elevated The mean values standard deviationsof the no NT-ProBNP NT-ProBNP elevated and normalsubgroups can be summarized in Table 2

Table 2 shows that no significant difference was observedbetween the NT-ProBNP elevated versus normal subgroupsor the NT-ProBNP normal and no NT-ProBNP subgroupson age predialysis weight estimated dry weight and volumeremoved Similar findings were detected for the predialysisweight estimated dryweight and volume removed (119875 = 049and 119875 = 042 119875 = 048 resp) of the NT-ProBNP elevatedsubgroup versus the no NT-ProBNP subgroup Howeverthere was a significant difference among the ages of thesegroups (119875 = 001)

32 CorrelationCoefficients of NT-ProBNP Correlation coef-ficients were calculated to examine correlation between theNT-ProBNP test and mean age EDW amount of fluidremoved and EF Linear regression and slope calculationyielded no correlation between the NT-ProBNP test and age(119903 = 005) EDW (119903 = minus009) amount of volume removed(119903 = 007) and EF (119903 = 002)

33 Incidence of Cardiology Parameters among SubgroupsAmid the cardiology parameters 165 or 552 of NT-ProBNPelevated subjects received a cardiology consult and 587of subjects received an echocardiogram with a mean EF of546This is comparable to 50 of the NT-ProBNP normalgroup and 455 of the no NT-ProBNP group receivingboth cardiology consult and echocardiography The ejectionfractions of these groups are 508 and 455 showing no

significant difference when compared with the EF of theelevated subgroup (119875 = 043 and 055 resp)

Similar symmetry was detected when measuring otherechocardiography parameters TheMean RVEFs were 382375 and 409 for the NT-ProBNP elevated normal andno NT-ProBNP groups respectively The mean mitral valveareas (MVA) were 42 cm2 46 cm2 and 45 cm2 respectivelyThemeanmitral valve gradients were 34mmHg 42mmHgand 37mmHg The tricuspid valve parameters yielded amean jet area-central jets at under 5 cm2 for each groupThe mean vena contracta width was not defined in eachgroup indicating normal valuesThemean pulmonary arterysystolic pressures of theNT-ProBNP elevated normal and noBNP groups were 201mmHg 224mm Hg and 197mmHgrespectively

The mean left atrial volumes were 473 455 and 392mLrespectively The mean Left ventricular masses for the ele-vated normal and no NT-ProBNP groups were 1488 grams(g) 1392 g and 1567 g respectively Lastly the EErsquo ratiowereall above 15 in each group reported A summary of theseresults can be seen in Table 4

34 Subanalysis of Extreme Groups Using the data collectedan extreme group of patients were identifiedThe 239 patientswithNT-ProBNP levels were divided into quartilesThe lowerquartile (le25)was labeled as the ldquolow grouprdquo and had levelswhich corresponded to 5676 pgmL and below The upperquartile (ge75) was labeled as the ldquohigh grouprdquo and hadNT-ProBNP levels which corresponded to 32499 pgmL andaboveTherewere 60 subjects in the low group and 61 subjectsin the high group (Figure 2)


250 hemodialysis patients with dyspnea presenting to Cooper University Hospital from July 2010 to March 2011

235 patients had NT-ProBNP performed Incidence 94

High group Low group

235 subjects were divided into quartiles The subjects with NT-ProBNP levels that fell within the 26thndash74th

percentile were excluded from the subanalysis

Fisherrsquos exact test used to analyze the difference between the high and low groups in the following

Pearson Chi-square used to analyze the difference between the high and low groups in

Frequency of cardiology consultsFrequency of echocardiograms ordered

Mann-Whitney U Test used to analyze the difference in means between the high and low groups in the following

Ultrafiltration (liters)Weight change (kg)Ejection fraction ()

NT-ProBNP levelsge32499 pgmL(ge75 percentile)

NT-ProBNP levelsle5676 pgmL(le25 percentile)

Frequency of performing hemodialysis

Figure 2 Subject selection of extreme quartiles

Analysis between the two groups to assess the differencein the frequency of performing hemodialysis was done usinga Fisherrsquos exact test Fifty-five out of 59 (932) subjects inthe low group underwent hemodialysis while all 61 (100)subjects in the high group had hemodialysis There was amarginal statistical difference between the two groups (119875 lt005)

A Pearson Chi-Square analysis was performed betweenthe low and high groups to assess the difference in thefrequency of ordering cardiology consults and echocardio-grams Cardiology consults were ordered in 33 out of 58(569) subjects in the low group while 47 out of 61 (77)subjects in the high group had cardiology consults Therewas a significant difference between both groups (119875 =002) In the low group 29 out of 60 (483) subjects hadechocardiograms ordered compared to 39 out of 61 (639)from the high group There was no significant differencebetween the two groups in ordering echocardiograms (119875 =008)

A Mann-Whitney U Test evaluated the difference involume of fluid removal weight change and ejection fractionbetween low and high groups (Table 3) The mean ultrafil-tration for the low group was 211 liters (119899 = 59) compared

to 248 liters for the high group (119899 = 61) The mean weightchange was 229 kg for the low group (119899 = 59) and was270 kg for the high group (119899 = 61) Low group (119899 = 60)ejection fraction mean was 542 compared to 5066 forthe high group (119899 = 61) There was no statistically significantdifference between the low and high groups in terms ofvolume of fluid removal (119875 = 014) and weight change(119875 = 022) There was a statistically significant difference inejection fraction (119875 = 002)

4 Discussion

To examine the utility of the NT-ProBNP test in the setting ofacute dyspnea for subjects with ESRD on HD one must firstunderstand the testrsquos molecular structure Brain NatriureticPeptide is a 32-amino acid polypeptide secreted by theventricles in response to stretch [19ndash21] Similarly a 76-amino acid N-terminus fragment of the BNP (NT-ProBNP)hormone is also secreted as the inactive componentThe NT-ProBNPmolecule is a cleaved molecule from ProBNP whichis exclusively secreted by the kidneys via endocytosis [20 21]In the setting of normal renal function BNP has a 20-minutehalf-life and for NT-BNP 1 to 2 hours [10ndash13] It is for this


Table2Mean

median

andstandard

deviationof

subgroup

sviasysto

licfunctio

n

NT-ProB

NPgrou

pEF

()

Creatin

ine1

HD

perfo

rmed

Volume

removed

2

Weight

priorto

dialysis3

Weight

after

dialysis3

Cardiology

consult

ECHO

Furosemide

Infectious

disease

consult

Antibiotics

NoNT-ProB

NP

lt45

119873

Valid

66

66

66

66

66

Mean

895

100

243

7257

6877

000

000

000

033

033

Median

990

100

200

6770

6500

000

000

000

000

000

Std

deviation

391

000

140

1050

1013

000

000

000

052

052

ge45

119873

Valid

55

55

55

55

55

Mean

800

100

200

7720

7568

100

100

020

020

020

Median

810

100

200

7430

6865

100

100

000

000

000

Std

deviation

239

000

000

1434

1808

000

000

045

045

045

NT-ProB

NPno

rmal

lt45

119873

Valid

11

11

11

11

11

Mean

1045

000

000

13634

13634

100

000

000

000

000

Median

1045

000

000

13634

13634

100

000

000

000

000

ge45

119873

Valid

44

44

44

44

44

Mean

923

075

228

7873

7778

050

075

000

025

025

Median

660

100

255

7250

7135

050

100

000

000

000

Std

deviation

852

050

172

1466

1442

058

050

000

050

050

NT-ProB

NPele

vated

lt45

119873

Valid

4949

4949

4949

4948

4949

Mean

600

098

245

7236

7160

059

049

160

012

014

Median

560

100

200

7250

7038

100

000

000

000

000

Std

deviation

231

014

114

2097

1928

050

051

655

033

035

ge45

119873

Valid

185

185

185

185

185

185

185

185

185

185

Mean

669

098

244

8188

7910

074

061

072

009

012

Median

610

100

200

7590

7250

100

100

000

000

000

Std

deviation

328

015

113

2496

2469

044

049

576

028

033

1 Creatinineinmilligramsd

eciliter(mgdL

)2 hem

odialysis

perfo

rmed

inlitersand

3 weightinkilogram

s(kg)


Table 3 Comparison of the high NT-ProBNP and low NT-ProBNP quartiles1 using the Mann-Whitney U Test

Group 119873 Mean Standard deviation 119875 value

Ultrafiltration (liters) Low 59 211 118 014High 61 248 116

Weight change (kg) Low 59 229 165 022High 61 270 166

Ejection Fraction () Low 60 5420 1822 002High 61 5066 1591

1Low group NT-ProBNP levels le5676 pgmL (le25 percentile)High group NT-ProBNP levels ge32499 pgmL (ge75 percentile)

Table 4 The Echocardiography parameters of the NT-ProBNP elevated NT-ProBNP normal and no NT-ProBNP groups

NT-ProBNP No NT-ProBNP 119875 Value (95 CI)NT-ProBNP elevated NT-ProBNP normal

Left ventricle parametersLeft ventricular systolic ejection fraction ()1 546 50 455 043Left atrial volume (mL)2 473 455 392 066Left ventricular mass (g)3 1488 1392 1567 045EE1015840 ratio gt15 gt15 gt15 10

Tricuspid parametersJet area-central jets (cm2)4 lt5 lt5 lt5 10Vena contracta width Not defined Not defined Not defined NA

Mitral valve parametersMitral valve areas (cm2)4 42 46 45 087Mitral valve gradient (mmHg)5 34 42 37 063

Right ventricular parametersRight ventricular ejection fraction ()1 382 375 409 046

Pulmonary artery parametersPulmonary artery systolic pressures (mmHg)5 201 224 197 024

1Percent () 2mililiters (mL) 3grams (g) 4centimeters squared (cm2) and 5milimeters of Mercury (mmHg)

reason that we chose the NT-ProBNP test instead of the BNPtest to determine LVSD in patients with ESRD on HD whopresented to the emergency department with acute dyspnea

Both of these hormones have been used in patients pre-senting with a chief complaint of dyspnea to predict whetherLeft Ventricular Systolic Dysfunction (LVSD) is the cause fortheir symptomsThe Breathing Not Properly data and studiesby Morrison et al demonstrated a positive predictive value(PPV) of greater than 90 for predicting congestive heartfailure as the etiology of patients presenting with dyspnea tothe emergency department [1ndash5] The sensitivity of the BNPassay has been reported to be 90 and specificity of 76if serum concentrations are greater than 100 picograms permilliliter(pgmL) for BNP and 500 pgmL for NT-ProBNPfor predicting CHF in patients presenting with dyspnea [67] Thus with a high pretest probability members of theemergency department utilize the NT-ProBNP and BNP totreat patients presenting with dyspnea

This ability has prompted diagnostic algorithms in emer-gency departments across the country for utilizing the NT-ProBNP as a marker for determining the etiology of peoplepresenting with shortness of breath However in circum-stance of renal dysfunction the diagnostic ability of NT-ProBNP test may be less apparent [14ndash16] It has been clearly

demonstrated that the BNP testing has prognostic ability inpatients with ESRD [22ndash26] Despite the prognostic ability oftheBNP test clinicians lack clear data on the diagnostic utilityof this test in the setting of ESRD on HD

Our study demonstrated that 956 of the sample pop-ulation received a NT-ProBNP test among which 98 wasdetermined to be an ldquoelevatedrdquo test Following the diagnosticalgorithm an elevated NT-ProBNP would likely correlatewith ordering of an echocardiogram or cardiology to assessLV systolic function (LVSF) Although the test was shownby Satyan et al to correlate with LV dysfunction we couldnot find any clinical value in determining disposition ofemergency room patients [27] Yet despite this similarpercentages of the study population received both cardiologyconsultation and echocardiography even when comparingthe NT-ProBNP elevated group with the NT-ProBNP normaland the group in which no test was performed (Table 2)

Using a similar logic there were no significant differ-ences found between the predialysis weights EDW volumesremoved or EFs when comparing the NT-ProBNP elevatedwith the NT-ProBNP normal and the group in which notest was performed (Table 2) To further illustrate this pointechocardiographic parameters were examined Across eachgroup there were no significant differences found between


these parameters as exemplified in Table 4 All of this datapoints away from the diagnostic utility of theNT-ProBNP testin this setting

In the extreme cases of low versus high NT-ProBNPlevels there was a marginally statistical difference in man-agement as evidenced by a higher incidence of performinghemodialysis and ordering cardiology consults in the groupwith the upper quartile NT-ProBNP There was howeverno significant difference found in the volume of fluidremoval and the weight change between pre- and postdialysis(Table 3)

Potential limitations of this study included the lack of dataon subjects receiving a BNP test Another potential limitationis that data was gathered retrospectively This study also doesnot take into account individual cases but rather trendsin our sample population Attempts to counteract thesepotential limitations will be made through future prospectivestudies to examine the utility of the NT-ProBNP test as wellas BNP test

5 Conclusion

In patients with ESRD on HD who presented to the EDwith acute dyspnea there is no significant difference inthe incidence of cardiologyinfectious disease consultationfurosemideantibiotics administration Additionally no dif-ference was seen in the incidence of neither echocardio-graphy ordered nor the parameters measured by standardechocardiography means

Disclosure

Theauthors of this paper required no funding for the creationof this study Additionally the authors have no financialdisclosures to report This article has not been submitted toany other journal and its text is original

Acknowledgments

S R S Mok was the primary investigator gathered themajority of the study data and composed the majority ofthe paper J Avila gathered data on the extreme quartilesand composed that portion of the paper B Milcarek did thestatistical analysis of the study R Kasama was the FacultyAdvisor and created the concept of this paper The writersof this paper would like to acknowledge the members of theMedical Records Department at Cooper University Hospitaland the Physicians and staff of Cooper University Hospital atRowan University

References

[1] L K Morrison A Harrison P Krishnaswamy R KazanegraP Clopton and A Maisel ldquoUtility of a rapid B-natriureticpeptide assay in differentiating congestive heart failure fromlung disease in patients presenting with dyspneardquo Journal of theAmerican College of Cardiology vol 39 no 2 pp 202ndash209 2002

[2] P AMcCullough J E Hollander RMNowak et al ldquoUncover-ing heart failure in patients with a history of pulmonary disease

rationale for the early use of B-type natriuretic peptide in theemergency departmentrdquoAcademic EmergencyMedicine vol 10no 3 pp 198ndash204 2003

[3] Q Dao P Krishnaswamy R Kazanegra et al ldquoUtility of B-TypeNatriuretic Peptide (BNP) in the diagnosis of CHF in an urgentcare settingrdquo Journal of the American College of Cardiology vol37 pp 379ndash385 2001

[4] M Davis E Espiner G Richards et al ldquoPlasma brain natri-uretic peptide in assessment of acute dyspneardquoThe Lancet vol343 pp 440ndash444 1994

[5] A Maisel P Krishnaswamy R M Nowak et al ldquoRapidmeasurement of B-type natriuretic peptide in the emergencydiagnosis of heart failurerdquoTheNewEngland Journal ofMedicinevol 347 no 3 pp 161ndash167 2002

[6] A Strunk V Bhalla P Clopton et al ldquoImpact of the historyof congestive heart failure on the utility of B-type natriureticpeptide in the emergency diagnosis of heart failure resultsfrom the breathing not properly multinational studyrdquoAmericanJournal of Medicine vol 119 no 1 pp 69e1ndash69e11 2006

[7] C K Brenden J E Hollander D Guss et al ldquoGray zone BNPlevels in heart failure patients in the emergency departmentresults from the Rapid Emergency Department Heart Fail-ure Outpatient Trial (REDHOT) multicenter studyrdquo AmericanHeart Journal vol 151 no 5 pp 1013ndash1018 2006

[8] J Pimenta F Sampaio P Martins et al ldquoAminoterminal B-type natriuretic peptide (NT-proBNP) in end-stage renal failurepatients on regular hemodialysis does it have diagnostic andprognostic implicationsrdquo NephronmdashClinical Practice vol 111no 3 pp c182ndashc188 2009

[9] L Sun Y Sun X Zhao et al ldquoPredictive role of BNP and NT-proBNP in hemodialysis patientsrdquo Nephron Clinical Practicevol 110 no 3 pp c178ndashc184 2008

[10] S Anwaruddin D M Lloyd-Jones A Baggish et al ldquoRenalfunction congestive heart failure and amino-terminal pro-brain natriuretic peptide measurement results from theProBNP investigation of dyspnea in the emergency department(PRIDE) studyrdquo Journal of the American College of Cardiologyvol 47 no 1 pp 91ndash97 2006

[11] C R DeFilippi S L Seliger SMaynard and RH ChristensonldquoImpact of renal disease on natriuretic peptide testing for diag-nosing decompensated heart failure and predicting mortalityrdquoClinical Chemistry vol 53 no 8 pp 1511ndash1519 2007

[12] C Bruch H Reinecke J Stypmann et al ldquoImpact of renaldisease on natriuretic peptide testing for diagnosing decompen-sated heart failure and predicting mortalityrdquo Journal of Heartand Lung Transplantation vol 25 no 9 pp 1135ndash1141 2006

[13] S Dhar G S Pressman S Subramanian et al ldquoNatriureticpeptides and heart failure in the patient with chronic kidneydisease a review of current evidencerdquo Postgraduate MedicalJournal vol 85 no 1004 pp 299ndash302 2009

[14] J RacekHKralova L Trefil D Rajdl and J Eiselt ldquoBrain natri-uretic peptide and N-terminal proBNP in chronic haemodial-ysis patientsrdquo NephronmdashClinical Practice vol 103 no 4 ppc162ndashc172 2006

[15] A Y Wang C W Lam C M Yu et al ldquoN-terminal pro-brainnatriuretic peptide an independent risk predictor of cardio-vascular con- gestion mortality and adverse cardiovascularoutcomes in chronic peritoneal dialysis patientsrdquo Journal of theAmerican Society of Nephrology vol 18 pp 321ndash330 2007

[16] I A Khan J Fink C Nass H Chen R Christenson andC R deFilippi ldquoN-terminal pro-brain natriuretic peptide


an independent risk predictor of cardiovascular con- gestionmortality and adverse cardiovascular outcomes in chronicperitoneal dialysis patientsrdquo American Journal of Cardiologyvol 97 no 10 pp 1530ndash1534 2006

[17] RM LangM Bierig R B Devereux et al ldquoRecommendationsfor chamber quantification a report from the American Societyof Echocardiographyrsquos guidelines and standards committee andthe Chamber Quantification Writing Group developed in con-junction with the European Association of Echocardiographya branch of the European Society of Cardiologyrdquo Journal of theAmerican Society of Echocardiography vol 18 no 12 pp 1440ndash1463 2005

[18] M A Quinones A D Waggoner and L A Reduto ldquoAnew simplified and accurate method for determining ejectionfraction with two-dimensional echocardiographyrdquo Circulationvol 64 no 4 pp 744ndash753 1981

[19] J P Henry and J W Pearce ldquoThe possible role of cardiac atrialstretch receptors in the induction of changes in urine flowrdquoTheJournal of Physiology vol 131 no 3 pp 572ndash585 1956

[20] R Klinge M Hystad J Kjekshus et al ldquoAn experimental studyof cardiac natriuretic peptides as markers of development ofCHFrdquo Scandinavian Journal of Clinical amp Laboratory Investiga-tion vol 58 pp 683ndash691 1998

[21] K Hosoda K NakaoMMukoyama et al ldquoExpression of brainnatriuretic peptide gene in human heart production in theventriclerdquo Hypertension vol 17 no 6 pp 1152ndash1155 1991

[22] W J Austin V Bhalla I Hernandez-Arce et al ldquoCorrelationand prognostic utility of B-type natriuretic peptide and itsamino-terminal fragment in patients with chronic kidneydiseaserdquo American Journal of Clinical Pathology vol 126 no 4pp 506ndash512 2006

[23] K S Spanaus F Kronenberg E Ritz et al ldquoB-type natriureticpeptide concentrations predict the progression of nondiabeticchronic kidney disease the mild-to-moderate kidney diseasestudyrdquo Clinical Chemistry vol 53 no 7 pp 1264ndash1272 2007


[25] M H Rosner ldquoMeasuring risk in end-stage renal disease is N-terminal pro brain natriuretic peptide a useful markerrdquoKidneyInternational vol 71 no 6 pp 481ndash483 2007

[26] L H Madsen S Ladefoged P Corell M Schou P R Hilde-brandt and D Atar ldquoN-terminal pro brain natriuretic peptidepredicts mortality in patients with end-stage renal disease inhemodialysisrdquo Kidney International vol 71 no 6 pp 548ndash5542007

[27] S Satyan R P Light and R Agarwal ldquoRelationships of N-terminal pro-B-natiuretic peptide and cardiac troponin T to leftventricular mass and function and mortality in asymptomatichemodialysis patientsrdquo American Journal of Kidney Diseasesvol 50 no 6 pp 1009ndash1019 2007

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Table 1 Sample population demographics

NT-ProBNP No NT-ProBNP Total (119899 = 250)NT-ProBNP elevated NT-ProBNP normal

Mean age1 583 518 466 577Sex

Males 108 2 2 112Females 127 2 9 138

RaceBlack 98 1 3 102White 65 0 6 71Hispanic 71 3 2 76Asian 1 0 0 1Other 0 0 0 0

1Units = years

admissions where and ESRD patient presented with dyspneaWe conclude that this diagnostic purpose NT-ProBNP playsno role in the management of hemodialysis patients

2 Materials and Methods

21 Study Design This study was approved by the CooperUniversity Hospital Institutional Review Board and was incompliance with the regulations set forth by the Declarationof Helsinki It was designed as a retrospective case seriesof 250 subjects with medical record abstraction beginningfrom March 31 2011 and working backward in time to July2010 Eligible patients 18 years or older were admitted toCooper University Hospital with the diagnosis code of ICD-9= 5856 or end-stage renal disease on hemodialysis (ESRD onHD) presenting with acute symptoms of dyspnea shortnessof breath or respiratory distress This excluded patientswithout end-stage renal failure and subjects not on HD Wealso excluded subjects who presented with complaints otherthan shortness of breath chronic respiratory complaintssubjects under 18 and undergoing peritoneal dialysis or acutehemodialysis

The sample was described in terms of age (years) sexrace weight prior to dialysis and estimated dry weight(kg) creatinine (mgdL) NT-ProBNP (pgmL) hemodialysiswas within 24 hours of admission (yesno) and volumeremoved (L) cardiology consultation placed (yn) echocar-diogram performed (yn) and estimated ejection fraction() furosemide administration (yn) infectious disease con-sultation placed (yn) and administration of antibiotics (yn)

For purposes of analysis patients were categorized intoone of three groups NT-ProBNP elevated (elevated test forage) NT-ProBNP normal (test within normal range for age)or noNT-ProBNP (test not performed) NT-ProBNPpatientswere further categorized as either normal ejection fraction(EF ge 45) or low ejection fraction (lt45)

22 Study Measurements Patient subgroups were tested forsignificant differences on NT-ProBNP creatinine weight(pre-post-HD) and volume fluid removed during HDWeight was calculated by standardized measurements on

scales ldquozeroedrdquo daily by hospitals quality control staff Vol-ume removed was extrapolated from the medical record bynephrology attending physician using notes on the actualamount of postdialysis fluid removed from the patientSerum creatinine was measured by spot venous 5 samplingcentrifugation storage at minus20 degrees Celsius and thenanalyzed via Isotope Dilution Mass Spectrometry (IDMS) orstandard measurements NT-ProBNP samples were collectedby similar means as the creatinine and measured by electro-chemiluminescence immunoassay Again both laboratory-testing devices are ldquozeroedrdquo daily by laboratory staff

Cardiology staff estimated ejection fraction primar-ily by transthoracic echocardiography (TTE) M-modetwo-dimensional imaging and spectralcolor flow Dopplerrecording were obtained Measurement we performed usingshort-axis parasternal long axis and apical 2 and 4 chamberviews Measurements were performed by guidelines set forthby the American Society of Echocardiography using theQuinones formula for the parasternal long-axis Simpsonmethod in the 2 and 4 chamber views [17 18] Parametersgathered included Left Ventricular Ejection Fraction (LVEF)Right Ventricular Ejection Fraction (RVEF) quantification ofmitral regurgitation quantification of tricuspid regurgitationestimated systolic pulmonary artery pressure left atrial vol-ume left ventricular mass and EE1015840

23 Statistical Analysis Differences between subgroups andcategorical variables were tested for significance by PearsonX2 or Fishers exact test Mean differences between subgroupswere tested for significance by independent samples t-testsOverall or group specific standard deviations were useddepending on Levenersquos test for homogeneity of variancesAssociations between continuous measures were calculatedusing the Pearson correlation coefficient with effect sizedefined as the coefficient of determination

3 Results

31 Subgroup Analysis As seen in Table 1 the study popula-tion did not differ in age sex or weight When further exam-ining the study population disbursement Figure 1 shows that



to March 2011





5 patients with NT-


EF ge45 EF lt45































4 Discussion



Table2Mean

median

andstandard

deviationof

subgroup

sviasysto

licfunctio

n

NT-ProB

NPgrou

pEF

()

Creatin

ine1

HD

perfo

rmed

Volume

removed

2

Weight

priorto

dialysis3

Weight

after

dialysis3

Cardiology

consult

ECHO

Furosemide

Infectious

disease

consult

Antibiotics

NoNT-ProB

NP

lt45

119873

Valid

66

66

66

66

66

Mean

895

100

243

7257

6877

000

000

000

033

033

Median

990

100

200

6770

6500

000

000

000

000

000

Std

deviation

391

000

140

1050

1013

000

000

000

052

052

ge45

119873

Valid

55

55

55

55

55

Mean

800

100

200

7720

7568

100

100

020

020

020

Median

810

100

200

7430

6865

100

100

000

000

000

Std

deviation

239

000

000

1434

1808

000

000

045

045

045

NT-ProB

NPno

rmal

lt45

119873

Valid

11

11

11

11

11

Mean

1045

000

000

13634

13634

100

000

000

000

000

Median

1045

000

000

13634

13634

100

000

000

000

000

ge45

119873

Valid

44

44

44

44

44

Mean

923

075

228

7873

7778

050

075

000

025

025

Median

660

100

255

7250

7135

050

100

000

000

000

Std

deviation

852

050

172

1466

1442

058

050

000

050

050

NT-ProB

NPele

vated

lt45

119873

Valid

4949

4949

4949

4948

4949

Mean

600

098

245

7236

7160

059

049

160

012

014

Median

560

100

200

7250

7038

100

000

000

000

000

Std

deviation

231

014

114

2097

1928

050

051

655

033

035

ge45

119873

Valid

185

185

185

185

185

185

185

185

185

185

Mean

669

098

244

8188

7910

074

061

072

009

012

Median

610

100

200

7590

7250

100

100

000

000

000

Std

deviation

328

015

113

2496

2469

044

049

576

028

033


eciliter(mgdL

)2 hem

odialysis

perfo

rmed

inlitersand

3 weightinkilogram

s(kg)


























5 Conclusion


Disclosure


Acknowledgments


References




































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of


















to March 2011





5 patients with NT-


EF ge45 EF lt45































4 Discussion



Table2Mean

median

andstandard

deviationof

subgroup

sviasysto

licfunctio

n

NT-ProB

NPgrou

pEF

()

Creatin

ine1

HD

perfo

rmed

Volume

removed

2

Weight

priorto

dialysis3

Weight

after

dialysis3

Cardiology

consult

ECHO

Furosemide

Infectious

disease

consult

Antibiotics

NoNT-ProB

NP

lt45

119873

Valid

66

66

66

66

66

Mean

895

100

243

7257

6877

000

000

000

033

033

Median

990

100

200

6770

6500

000

000

000

000

000

Std

deviation

391

000

140

1050

1013

000

000

000

052

052

ge45

119873

Valid

55

55

55

55

55

Mean

800

100

200

7720

7568

100

100

020

020

020

Median

810

100

200

7430

6865

100

100

000

000

000

Std

deviation

239

000

000

1434

1808

000

000

045

045

045

NT-ProB

NPno

rmal

lt45

119873

Valid

11

11

11

11

11

Mean

1045

000

000

13634

13634

100

000

000

000

000

Median

1045

000

000

13634

13634

100

000

000

000

000

ge45

119873

Valid

44

44

44

44

44

Mean

923

075

228

7873

7778

050

075

000

025

025

Median

660

100

255

7250

7135

050

100

000

000

000

Std

deviation

852

050

172

1466

1442

058

050

000

050

050

NT-ProB

NPele

vated

lt45

119873

Valid

4949

4949

4949

4948

4949

Mean

600

098

245

7236

7160

059

049

160

012

014

Median

560

100

200

7250

7038

100

000

000

000

000

Std

deviation

231

014

114

2097

1928

050

051

655

033

035

ge45

119873

Valid

185

185

185

185

185

185

185

185

185

185

Mean

669

098

244

8188

7910

074

061

072

009

012

Median

610

100

200

7590

7250

100

100

000

000

000

Std

deviation

328

015

113

2496

2469

044

049

576

028

033


eciliter(mgdL

)2 hem

odialysis

perfo

rmed

inlitersand

3 weightinkilogram

s(kg)


























5 Conclusion


Disclosure


Acknowledgments


References




































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of



































4 Discussion



Table2Mean

median

andstandard

deviationof

subgroup

sviasysto

licfunctio

n

NT-ProB

NPgrou

pEF

()

Creatin

ine1

HD

perfo

rmed

Volume

removed

2

Weight

priorto

dialysis3

Weight

after

dialysis3

Cardiology

consult

ECHO

Furosemide

Infectious

disease

consult

Antibiotics

NoNT-ProB

NP

lt45

119873

Valid

66

66

66

66

66

Mean

895

100

243

7257

6877

000

000

000

033

033

Median

990

100

200

6770

6500

000

000

000

000

000

Std

deviation

391

000

140

1050

1013

000

000

000

052

052

ge45

119873

Valid

55

55

55

55

55

Mean

800

100

200

7720

7568

100

100

020

020

020

Median

810

100

200

7430

6865

100

100

000

000

000

Std

deviation

239

000

000

1434

1808

000

000

045

045

045

NT-ProB

NPno

rmal

lt45

119873

Valid

11

11

11

11

11

Mean

1045

000

000

13634

13634

100

000

000

000

000

Median

1045

000

000

13634

13634

100

000

000

000

000

ge45

119873

Valid

44

44

44

44

44

Mean

923

075

228

7873

7778

050

075

000

025

025

Median

660

100

255

7250

7135

050

100

000

000

000

Std

deviation

852

050

172

1466

1442

058

050

000

050

050

NT-ProB

NPele

vated

lt45

119873

Valid

4949

4949

4949

4948

4949

Mean

600

098

245

7236

7160

059

049

160

012

014

Median

560

100

200

7250

7038

100

000

000

000

000

Std

deviation

231

014

114

2097

1928

050

051

655

033

035

ge45

119873

Valid

185

185

185

185

185

185

185

185

185

185

Mean

669

098

244

8188

7910

074

061

072

009

012

Median

610

100

200

7590

7250

100

100

000

000

000

Std

deviation

328

015

113

2496

2469

044

049

576

028

033


eciliter(mgdL

)2 hem

odialysis

perfo

rmed

inlitersand

3 weightinkilogram

s(kg)


























5 Conclusion


Disclosure


Acknowledgments


References




































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Table2Mean

median

andstandard

deviationof

subgroup

sviasysto

licfunctio

n

NT-ProB

NPgrou

pEF

()

Creatin

ine1

HD

perfo

rmed

Volume

removed

2

Weight

priorto

dialysis3

Weight

after

dialysis3

Cardiology

consult

ECHO

Furosemide

Infectious

disease

consult

Antibiotics

NoNT-ProB

NP

lt45

119873

Valid

66

66

66

66

66

Mean

895

100

243

7257

6877

000

000

000

033

033

Median

990

100

200

6770

6500

000

000

000

000

000

Std

deviation

391

000

140

1050

1013

000

000

000

052

052

ge45

119873

Valid

55

55

55

55

55

Mean

800

100

200

7720

7568

100

100

020

020

020

Median

810

100

200

7430

6865

100

100

000

000

000

Std

deviation

239

000

000

1434

1808

000

000

045

045

045

NT-ProB

NPno

rmal

lt45

119873

Valid

11

11

11

11

11

Mean

1045

000

000

13634

13634

100

000

000

000

000

Median

1045

000

000

13634

13634

100

000

000

000

000

ge45

119873

Valid

44

44

44

44

44

Mean

923

075

228

7873

7778

050

075

000

025

025

Median

660

100

255

7250

7135

050

100

000

000

000

Std

deviation

852

050

172

1466

1442

058

050

000

050

050

NT-ProB

NPele

vated

lt45

119873

Valid

4949

4949

4949

4948

4949

Mean

600

098

245

7236

7160

059

049

160

012

014

Median

560

100

200

7250

7038

100

000

000

000

000

Std

deviation

231

014

114

2097

1928

050

051

655

033

035

ge45

119873

Valid

185

185

185

185

185

185

185

185

185

185

Mean

669

098

244

8188

7910

074

061

072

009

012

Median

610

100

200

7590

7250

100

100

000

000

000

Std

deviation

328

015

113

2496

2469

044

049

576

028

033


eciliter(mgdL

)2 hem

odialysis

perfo

rmed

inlitersand

3 weightinkilogram

s(kg)


























5 Conclusion


Disclosure


Acknowledgments


References




































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of









































5 Conclusion


Disclosure


Acknowledgments


References




































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of


































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















Research Article The NT-ProBNP Test in Subjects with End-Stage...

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