Journal of Pathology and Laboratory Medicine

Vol. 1(1), pp. 002-007, January, 2020. © www.premierpublishers.org, ISSN: 2435-3496

Research Article
Does Type of Dialysis Affect BNP in Fluid Overload Patients?
*Elmas Öğüş1, Fatma Meriç Yılmaz2, Nermin Dindar3, Hatice Akay4, Nurçin Tekeli5, Murat
Duranay6, Doğan Yücel7
Department of 1,2,3,7Medical Biochemistry, 4,5,6Dialysis, Ankara Training and Research Hospital, Health Sciences
University, Ankara, Turkey

Brain Natriuretic Peptide (BNP) levels are important as predictors of heart failure in end-stage
renal disease (ESRD) patients undergoing hemodialysis (HD) and continuous ambulatory
peritoneal dialysis (PD). Twenty-four HD patients and 35 PD patients were included in the study.
Each patient underwent an echocardiographic examination besides the determination of BNP,
high-sensitivity C-reactive protein (hs-CRP) and homocysteine (Hcy). BNP, left ventricular mass
(LVM), left ventricular mass index (LVMI) and Hcy levels were significantly higher in HD group
(p<0.05); hs-CRP levels were significantly higher in PD group (p=0.029). Predialysis BNP was
significantly higher than the postdialysis BNP (p=0.003). There was a significant correlation
between LVMI and BNP in PD (r=0.527, p=0.009) and predialysis BNP in HD (r=0.417, p=0.043)
groups. In conclusion, BNP levels were found to be significantly correlated with LVMI in HD and
PD patients. Hemodialysis patients had higher BNP and LVMI levels. This may be due to the
hemodynamic changes which occur with the hemodialysis.

Keywords: Brain Natriuretic Peptide, Left Ventricular Hypertrophy, Heart Failure, Hemodialysis, Peritoneal Dialysis

INTRODUCTION

Atrial natriuretic peptide (ANP) and brain natriuretic
peptide (BNP) are the members of the natriuretic peptide
family. They have been studied as possible markers of
increased cardiovascular risk. BNP is generated by
ventricular myocytes and its production rate is amplified by
heart failure or left ventricular hypertrophy (LVH)
(Mukoyama M 1991, Yasue H et al 1994). BNP is
synthesized as preproBNP in the ventricular myocardium,
enzymatically cleaved to proBNP and released in the form
of hormonally active BNP and the inactive N-terminal
proBNP (NT-proBNP). BNP and NT-proBNP, both can be
used in diagnosing heart failure. However, NT-proBNP is
eliminated mainly by glomerular filtration in contrast to
BNP which is eliminated mainly through natriuretic peptide
receptors and degrated by neutral endopeptidases in
addition to glomerular filtration (Wahl HG et al 2004).
Cardiovascular risk stratification is important in the clinical
management of patients with end-stage renal disease
(ESRD) and cardiovascular biomarkers are increasingly
used in these patients. Natriuretic peptides are relatively
novel markers that can be used to identify and monitor
heart failure (Sundqvist S et al 2016, Roberts MA et al
2014). An increase of brain natriuretic peptide (BNP) levels
is commonly observed in patients on dialysis. Increased
circulating levels of BNP are related to future cardiac
events and associated with shorter survival in patients on
chronic HD (Taskapan MC et al 2006, Wang AY 2012).
Patients with chronic renal failure (CRF) are at high risk of
cardiovascular diseases, particularly congestive heart
failure (CHF). Left ventricular pathologies have priority in
these patients. In patients with chronic anemia who are
unresponsive to erythropoietin therapy, transfusion can be
performed according to the patient's clinical condition for
the treatment of anemia. Rapidly increasing blood volume
cannot be well tolerated by patients with chronic anemia
and transfusion-related circulatory overload (TACO) may
develop (Piccin A et al 2015). BNP measurements in
patients with congestive heart failure are independent
tests to determine long-term morbidity and mortality, and
repeated BNP measurements can be used to assess the
efficacy of treatment.
*Corresponding Author: Elmas Öğüş; Department of
Medical Biochemistry, Ankara Training and Research
Hospital, Health Sciences University, Ankara, Turkey.
Email: oguselmas@gmail.com; Tel: +90-312 5953215

Does Type of Dialysis Affect BNP in Fluid Overload Patients?

Öğüş et al. 003
Inflammatory markers are increased in chronic heart
failure (CHF), including high-sensitivity C-reactive protein
(hsCRP), but there is little information about its relationship
with prognosis or other prognostic markers (Windram JD
et al 2007). Hyperhomocysteinemia has been linked to
impaired left ventricular function and clinical condition in
patients with chronic heart failure. Homocysteine (Hcy)
stimulates myocardial brain natriuretic peptide (BNP)
expression and induces adverse left ventricular
remodeling (Herrmann M et al 2007).
This study is designed to investigate the diagnostic value
of BNP for left ventricular dysfunction in chronic renal
failure patients undergoing HD and PD. In our study, BNP
which is an indicator of cardiac volume load increase in HD
and PD patients was studied. Also we aimed to investigate
the relationship between BNP and echocardiografic
findings as well as Hcy and hs-CRP in both groups.
MATERIALS AND METHODS
Patients
A total number of 59 subjects (24 HD, 35 PD) were
included in the study. Cause of ESRD was pyelonephritis
in 2 patients, glomerulonephritis in 7 patients, hypertensive
nephropathy in 12 patients, diabetic nephropathy in 3
Table 1. Clinical Details of the Patients
HD
Sex, male/female 14/10
Age, year, mean, mean ± SD 46.7 ± 16.3
Duration of dialysis, month, mean ± SD 61.9 ± 48.0
BMI, kg/m2, mean ± SD 21.3 ± 2.87
Blood pressure, systolic, mmHg, mean ± SD 129 ± 17.3
Blood pressure, diastolic, mmHg, mean ± SD 75.0 ± 8.84
BMI: Body mass index
Biochemical Analyses
BNP was measured with a fluorescence immunoassay
system (Triage Biosite, San Diego, CA, USA). The Triage
BNP test is a single use device designed to determine the
concentration of BNP in EDTA-anticoagulated whole
blood. The test procedure involves the addition of several
drops of an EDTA whole blood specimen to the sample
port on the test device. After the specimen is added, the
device is inserted into the Triage Meter. The BNP analysis
were performed automatically after the sample has
reacted with the reagents within the test device and total
test time is approximately 15 minutes. hs-CRP was
measured with an Immage nephelometer (Beckman-
Coulter Inc. Fullerton, CA, USA); Hcy was determined with
reverse phase chromatography by an Agilent 1100 HPLC
analyzer (Agilent Technologies, Waldbronn-Germany),
using Chromsystems reagents (Chromsystems
Instruments and Chemicals GmbH, München, Germany).
Does Type of Dialysis Affect BNP in Fluid Overload Patients?
patients in HD group; pyelonephritis in 8 patients,
glomerulonephritis in 9 patients, hypertensive nephropathy
in 13 patients, and diabetic nephropathy in 5 patients in PD
group.
In this study, blood samples taken from outpatients
receiving dialysis treatment on weekdays in the dialysis
unit of our hospital were included. Patients who needed
transfusion according to their clinical status were
excluded. Therefore, the number is limited. Also, patients
with recent or subsequent infection undergoing dialysis
and peritoneal dialysis were excluded. Hemodialysis was
performed with high-flux polysulphone dialyzers (1.4-2.0
m2) (Fresenius Medical Care, Bad Homburg, Germany).
Peritoneal dialysis was performed using glucose
containing solutions four times a day (Dieneal; Baxter
Healthcare, Deerfield, IL, USA). Blood samples for BNP
were collected by venipuncture into EDTA tubes before
and after dialysis in HD and between 08:00 and 10:00 AM
before the first morning dwell in PD and were measured
immediately. Other blood samples were drawn into
Vacutainer® SST tubes at the same time for hs-CRP and
Hcy (in dark). After coagulation sera were separated and
frozen at -20 oC and stored in dark for Hcy. All of the
patients have given written informed consent and the study
was approved by Institutional Review Board of the
hospital. Clinical parameters of the groups are shown in
Table 1.
PD P
20/15
48.8 ± 15.5 >0.05
43.2 ± 38.5 0.003
24.9 ± 4.48 0.002
120 ± 18.5 >0.05
74.7 ± 11.3 >0.05
Echocardiography
All of the measurements were made according to the
recommendations of the American Society of
Echocardiography (Sahn DJ et al 1978). The
measurements of left ventricular end diastolic diameter,
posterior wall thickness and interventricular septum
thickness were obtained from M-mode echocardiography.
Left ventricular mass (LVM) was calculated with Devereux
formula and indexed to body surface area to obtain left
ventricular mass index (LVMI) (Devereux RB et al 1986).
Left ventricular hypertrophy (LVH) was defined as LVMI
greater than 125 g/m2 for both men and women (Koren MJ
et al 1991).
Statistical Analysis
Values are reported as mean ± SD or median (min/max)
for quantitative variables. Differences between the groups
 J. Pathol. Lab. Med. 004

Table 2. Biochemical Parameters of the Groups

Variable HD PD P
BNP, ng/L, median (min/max) 602 (105 - 4900) 132 (5 - 2830) 0.001*
LVM, g, mean ± SD 282 ± 56.4 234 ± 76.9 0.004*
LVMI, g/m2, mean±SD 176 ± 44.8 134 ± 42.6 0.001*
hs-CRP, mg/L, median (min/max) 4.7 (1 – 19.1) 13.1 (1 – 10.0) 0.029*
Hcy, µmol/L, median (min/max) 28.4 (10 - 236) 22.2 (6.37 - 56.4) 0.004*
Variable HD (Predialysis) HD (Postdialysis) P
BNP, ng/L, median (min/max) 602 (105 - 4900) 467 (111 - 3380) 0.003**
hs-CRP, mg/L, median (min/max) 4.7 (1 – 19.1) 4.3 (1 – 19.6) 0.073**
Data are presented as median (interquartile range) and mean±SD. BNP, brain natriuretic peptide; LVM: Left ventricular
mass; LVMI: Left ventricular mass index. Comparisons between HD and PD patients were run using *Mann-Whitney U
and **Wilcoxon tests. P<0.05 was considered statistically significant.

were compared using Mann-Whitney U test. BNP and hs-
CRP levels before and after hemodialysis session were
compared with Wilcoxon test. P<0.05 was considered
statistically significant. The strength of the association
between the variables were determined with the
Spearman correlation. Receiver operating characteristics
curve and area under the curve were presented for BNP
according to LVMI cut-off of 125 g/m2. Statistical analysis
were made using SPSS for Windows 15.0 (SPSS Inc.
Headquarters, Chicago, Ill., USA) software program.
The effects of dialysis types and hypertension were
analyzed alone and together with two-way ANOVA. Type
of dialysis is significantly effective of the BNP levels with
or without hypertension (p=0.005). Existence of
hypertension has no significant effect on the plasma BNP
levels (p=0.0638).
A ROC analysis of BNP was performed for predicting LVH
(Figure 2) and AUC was found to be 0.880 (95% CI=
0.798-0.962).

RESULTS

BNP levels of the subjects distributed in a wide range

(Figure 1). Thirteen patients in PD group and 22 patients
in HD group had a LVMI >125 g/m2. BNP, LVM, LVMI and
Hcy levels were significantly higher in HD group (p<0.05);
hs-CRP levels were significantly higher in PD group (p=
0.029). Predialysis BNP was significantly higher than the
postdialysis BNP (p= 0.003). hs-CRP levels were not
significantly different before and after hemodialysis
sessions (p= 0.073) (Table 2).

Figure 2. Receiver operating characteristic curve

1 10 100 1000 10000 analyzing the sensitivity and specificity of BNP in
BNP, ng/L predicting LVH
LVMI<125 LVMI>125

Figure 1. Distribution of BNP levels in LVH groups DISCUSSION

There was a significant correlation between LVMI and
BNP in PD (r= 0.527, p= 0.009) and predialysis BNP in HD
group (r= 0.417, p= 0.043). However, the correlation
between postdialysis BNP and LVMI was not statistically
significant (r= 0.333, p= 0.130).
In HD patients the level of BNP before and after
hemodialysis was more than 1.3 times higher.
In this study, we investigated BNP rather than NT-proBNP
as a marker of overload as BNP levels in dialysis patients
differ less from nondialysis subjects, and are less affected
by dialysis treatment modalities than are NT-proBNP
levels. Blood samples taken from outpatients receiving
dialysis treatment on weekdays in the dialysis unit of our
hospital were included. Patients who needed transfusion
according to their clinical status were excluded. Therefore,
the number is limited.

Does Type of Dialysis Affect BNP in Fluid Overload Patients?

Öğüş et al. 005
BNP levels were significantly correlated with LVMI both in
HD and PD patients. HD patients had higher BNP and
LVMI levels than PD patients. This may result from
hemodynamic changes due to volume overload and
subsequent hemodialysis. Another significant difference
between the groups was higher hs-CRP levels in PD group
despite exclusion of recent pass and subsequent short-
term infection.
Coronary heart disease incidence in dialysis patients
increases with age, male sex, diabetes, hypertension,
increased hs-CRP levels, hyperhomocysteinemia,
smoking, time on HD and inadequacy of HD (Soubassi LP
et al 2006). The possibility of using cardiac natriuretic
peptides for the diagnosis of LVH and systolic dysfunction
was investigated in early 1990s, which showed that the
measurement of these peptides, particularly BNP, has a
substantial potential for predicting anatomical and
functional alterations of the left ventricle (Yamamoto K et
al 1996). BNP is a sensitive marker of heart dysfunction.
Plasma levels of BNP increase in left ventricular failure and
determination of plasma BNP has become a useful tool in
the diagnosis of heart failure. HD patients may have
elevated plasma levels of BNP, particularly predialysis,
that correlate with echocardiographic signs of left
ventricular dysfunction. High BNP levels are also a strong
predictor of mortality in dialysis patients (Odar-Cederlöf I
et al 2006). Echocardiogram, which is a widely available
method, in the general population has a sensitivity that
may reach at most 40%, and it is used in dialysis patients
for the diagnosis of LVH (Schillaci G et al 1994). It has
been reported that the changes in LVMI have an
independent prognostic value for cardiovascular events
and provide scientific support for the use of repeated
echocardiographic studies for monitoring cardiovascular
risk in dialysis patients (Zoccali C et al 2004). However,
echocardiogram causes an additional burden to dialysis
patients. Hence, BNP may be useful for the assessment of
LVH in these patients. In previous studies it is shown that
elevated predialysis plasma BNP level in HD patients is
considered a sensitive and early indicator marker of left
ventricular dysfunction and correlates with
echocardiographic signs of left ventricular dysfunction that
decreased postdialysis (Odar-Cederlöf I et al 2006, Sheen
V et al 2007). A study by Vaičiūnienė et al (2017) showed
that the left ventricular hypertrophy was present in more
than half of prevalent hemodialysis patients and it was
related to hyperhydration detected by bioimpedance and
by lung ultrasound. In these patients the level of NTpro-
BNP before and after hemodialysis was more than 3 times
higher as compared with those without left ventricular
hypertrophy. Predialysis BNP levels have been reported to
decrease during conventional HD. In other studies, it is
reported that the plasma BNP levels are correlated to the
degree of fluid retention in HD patients. Researchers
confirmed that the BNP decrease in the first months of HD
therapy is related to fluid excess correction and BNP may
be a marker of overhydration in HD patients (Baki et al
2017, Chazot et al 2017, Shawky et al 2018, Stenberg et
al 2019).
Does Type of Dialysis Affect BNP in Fluid Overload Patients?
Our study is in agreement with previous studies with the
higher predialysis plasma BNP levels. However we did not
observe a significant correlation between postdialysis BNP
and LVMI in HD patients. In these patients, the level of
BNP before and after hemodialysis was more than 1.3
times higher. Further studies are needed for confirmation
of causal relation of these associations.
The correlation between plasma BNP concentration and
findings of echocardiography in HD and PD patients was
previously compared and plasma BNP levels were found
to be markedly greater in HD patients than those of PD
patients (Taskapan MC et al 2006, Nakatani T et al 2002),
suggesting that cardiac load in PD patients may be lower
than that of HD patients. Ludka et al (2013) reported that
the lower concentration of NT-proBNP in patients on
CAPD compared to those on HD suggests that CAPD
produces lesser hemodynamic stress, especially in
patients with preserved left ventricular systolic function.
The present study also showed that plasma BNP
concentration was significantly higher in HD patients than
in PD patients (602 ng/L and 132 ng/L, respectively, P
<0.001). However, there were significant differences in
either LVM or LVMI (P = 0.004; P <0.001) when HD
patients compared with PD patients, in our study; therefore
the results might be influenced from the study population.
Although the patients who needed transfusion according
to their clinical status were excluded, the BNP levels were
lower in PD patients than in HD patients, suggesting that
cardiac load in PD patients may be lower than that of HD
patients.
Type of dialysis is significantly effective of the BNP levels
with or without hypertension (p=0.005). Existence of
hypertension has no significant effect on the plasma BNP
levels (p=0.0638). This p value is near to alpha value of
the test (0.05). We think the effect of hypertension on BNP
levels would show statistical significance if the sample size
would be higher.
Blood BNP concentrations did not permit to decide a clear
cut-off value, so they were divided into classes that
“negative”, “gray-zone (intermediate)”, and “positive” for
predicting the left ventricular hypertropy. BNP
concentrations <100 ng/L were considered negative
(specificity 1.00, sensitivity 0.54, P <0.01). BNP
concentrations greater than a cut-off value of 330 ng/L
(specificity 0.667, sensitivity 1.00, P <0.01) were
considered positive. BNP concentrations between 100 and
330 ng/L fall into gray zone and were considered
intermediate.
Previously, the area under the ROC curves were reported
to be greater than 0.895 before and after hemodialysis (P
< 0.01) and using 152 ng/L as a cut-off value, predialysis
BNP was found to have 81% sensitivity and 83% specificity
in diagnosing left ventricular dysfunction in these patients
(Zeng C et al 2006). In our study using same cut-off value,
BNP found to have 89% of sensitivity and 63% of
specificity in diagnosing LVH in patients.

Inflammatory markers such as hs-CRP can provide an
adjunctive method for global assessment of cardiovascular
risk (Ridker PM 2001). The prevalence of inflammation is
high among patients with chronic renal failure but the
reason of inflammation is unclear. It could be the
consequence of an increased left-ventricular wall tension
related to ventricular dysfunction, hypervolemia or both
(Ortega O et al 2004).
In our study, HD and PD patients were evaluated for hs-
CRP, one of the markers of inflammation. The mean hs-
CRP levels were higher in the PD group compared to the
HD group and a significant difference was found between
them. These findings show higher inflammation in PD
patients compared to HD group. The causes of
inflammation; PD-related infections such as catheter exit
site infection, peritonitis. Because dialysis in PD patients is
performed by the patient under home conditions, HD
patients are performed by standard procedure in the
hospital. There was no significant difference in hs-CRP
levels between the before and after sessions in
hemodialysis patients. This excludes the presence of
problems with contamination of the dialysis fluids or the
location of the fistula.
Hyperhomocysteinemia is known to be another risk factor
for cardiovascular disease that seems also to be
associated with chronic heart failure. In previous studies it
was shown that hyperhomocysteinemia stimulates
myocardial brain natriuretic peptide expression (Herrmann
M et al 2007). In our study, we investigated the relationship
between hs-CRP, Hcy and BNP levels. We found that hs-
CRP levels were significantly higher; Hcy levels were
significantly lower in PD patients compared with HD
patients and there was no correlation between plasma
BNP and Hcy levels. There was not a significant
correlation between predialysis and postdialysis plasma
BNP and hs-CRP levels. This result showed that PD
patients may have a tendency to inflammation and
cardiovascular events and this result was in agreement
with previous studies (Yilmaz FM et al 2007, Bakkaloglu
SA et al 2009). However, hs-CRP is not useful for
assessment of LV dysfunction in chronic PD patients
(Wang AY-M et al 2009).
CONCLUSION
BNP levels were found to be significantly correlated with
LVMI in HD and PD patients. HD patients had higher BNP
and LVMI levels. This may be due to the hemodynamic
changes which occur with the hemodialysis.
Declaration of conflict of interest
None
Does Type of Dialysis Affect BNP in Fluid Overload Patients?
J. Pathol. Lab. Med. 006
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Accepted 27 November 2019
Citation: Öğüş E, Yılmaz FM, Dindar N, Akay H, Tekeli N,
Duranay M, Yücel D (2020). Does Type of Dialysis Affect
BNP in Fluid Overload Patients? Journal of Pathology and
Laboratory Medicine, 1(1): 002-007.
Copyright: © 2020: Öğüş et al. This is an open-access
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