Narrative Review

Use of Lung Ultrasound for the Assessment of Volume

Status in CKD
Adrian Covic, Dimitrie Siriopol,* and Luminita Voroneanu*

Adequate assessment of fluid status is an imperative objective in the management of all types of Complete author and article
patients in cardiology, intensive care, and especially nephrology. Fluid overload is one of the most information provided before
references.
common modifiable risk factors directly associated with hypertension, heart failure, left ventricular
hypertrophy, and eventually, higher morbidity and mortality risk in these categories of patients. Different *D.S. and L.V. contributed
methods are commonly used to determine fluid status (eg, clinical assessment, natriuretic peptide equally to this work.
concentrations, echocardiography, inferior vena cava measurements, or bioimpedance analysis). In Am J Kidney Dis. 71(3):
recent years, lung ultrasonography (LUS), through the assessment of extravascular lung water, has 412-422. Published online
received growing attention in clinical research. This article summarizes available studies that compare December 20, 2017.
LUS with other methods for fluid status assessment in patients with kidney diseases. At the same time, doi: 10.1053/
it also presents the association of LUS with different outcomes (physical functioning, mortality, and j.ajkd.2017.10.009
cardiovascular events) in the same population. It appears that this simple bedside noninvasive tech- © 2017 by the National
nique has significant clinical potential in nephrology. Kidney Foundation, Inc.

Introduction
Preservation of normohydration is an imperative objective
in the management of all types of patients in cardiology,
intensive care, and especially nephrology. Overhydration
is a common complication in these categories of patients.
When a combined dysfunction (heart and kidney) is
present, overhydration is almost the rule.1 Abnormal fluid
status increases blood pressure and cardiac preload,
contributing to left ventricular (LV) hypertrophy and
congestive heart failure.2 Thus, overhydration has been
linked with increased cardiovascular (CV) morbidity and
mortality.3 Similarly, in critically ill patients and those
with acute kidney injury, fluid accumulation has been
shown to worsen prognosis.4 The mortality rates at 30
days, 60 days, and hospital discharge are significantly
higher in patients with fluid overload.5 In patients with
septic shock, a more positive fluid balance at 12 hours and
day 4 has been found to correlate significantly with
increased mortality.6 Finally, in patients with chronic
kidney disease (CKD), fluid overload contributes to arte-
rial stiffness, atherosclerosis, and uremic cardiomyopa-
thy7 and is an independent risk factor for the combined
outcome of all-cause mortality or CV morbidity.3,8
Importantly, in patients with end-stage renal disease
(ESRD), not only is predialysis overhydration associated
with increased risk for death, but so is predialysis
underhydration.9
Assessment of Hydration Status–Easy and
Accurate?
The clinical evaluation of fluid status is imprecise and has
poor diagnostic accuracy. The simplest sign of hyper-
volemia, pitting pedal edema, is observed only when
overhydration is significant.10 Furthermore, edema can be
present without underlying overhydration, such as in the
case of increased vascular permeability, stasis, or treatment
with vasodilatory drugs, and as such has a limited value for
diagnosing excess intravascular volume.10
There are several objective methods available for the
optimal evaluation of patients’ hydration status: isotope
dilution and neutron activation analysis techniques are
considered as gold standards for total-body water and body
fluid compartments assessment.11 However, the use of
such methods is limited to the research environment. In
practice, several indirect methods are routinely used,
though all of them have several important limitations.
Ultrasound measurements of inferior vena cava (IVC)
diameter and the derived collapsibility index have been
shown to predict volume status, but they can only be used
to assess intravascular (preload) volume and not real tissue
hydration.12 Besides significant interoperator variability,13
the presence of diastolic dysfunction or right-sided cardiac
failure is a major limitation.
Natriuretic peptides (brain natriuretic peptide [BNP]
and N-terminal pro-brain natriuretic peptide [NT-
proBNP]) are well-studied biomarkers in patients with
heart failure (HF) or CKD. Their expression is promptly
upregulated when cardiomyocytes are stretched by preload
(usually overhydration) or afterload (usually hypertension
or increased arterial stiffness). Thus, biomarkers may
indicate changes in volume status, but are also heavily
influenced by intrinsic underlying CV disease and can
accumulate in severe CKD.
Bioelectrical impedance analysis (BIA) has been accepted
as a noninvasive and straightforward bedside technique to
measure body hydration status; it is economical, safe, and
portable and also provides information for fat and lean tissue
composition. That said, BIA measures body composition
indirectly, and the accuracy of BIA measurements largely
depends on mathematical models and their assumptions,
which have been validated only in select populations,
namely individuals of European descent who do not have
kidney disease.14 Adding to the complexity, a number of

412 AJKD Vol 71 | Iss 3 | March 2018

Narrative Review
different kinds of BIA have been developed in the last 15
years (single/multiple frequency and segmental/whole-
body bioimpedance). Nevertheless, in observational
studies of patients with CKD, BIA-assessed fluid overload
predicts mortality.15 Furthermore, this method may help
inform ultrafiltration prescription and thus improve hy-
pertension control and arterial stiffness16 and ultimately
reduce mortality risk in hemodialysis (HD) patients.17
Several limitations should be mentioned for this tech-
nique: (1) in pregnant women, children, and individuals
wearing a pacemaker, the accuracy of BIA can be reduced;
(2) measurements may be influenced by preceding intense
physical activity or food, alcohol, and fluid intake; values
are also affected by severe obesity and acute body mass
changes arising from protein malnutrition; and (3) in the
setting of ESRD, BIA cannot accurately assess weight (water)
change during HD.18,19 The basic limitation is a conse-
quence of the assumption that the human body is a cylinder
of uniform conductivity. The cross-sectional area of the
torso is relatively much larger than that of the extremities.
As a result, whole-body resistance is almost exclusively
(90%) a product of the resistance in the limbs (which have
lower fluid volume than the trunk). Given this, one
approach is to use segmental bioimpedance to remove the
effect of higher resistance in the arms and legs. Although
linking several segmental measurements would probably
provide a more precise description of body composition,
there is no strong evidence that this leads to superior hard
clinical outcomes. We also should not forget that BIA vali-
dation studies have generally been limited to healthy in-
dividuals. There are far more limited data for the elderly,
children and adolescents, or ethnic minorities. Entities that
vary markedly from the reference population will produce
measurements of limited validity and accuracy.
Lung Ultrasound
Extravascular lung water (ELW) represents a central
element of body fluid volume. It reflects the water content
of the lung interstitium, which is determined by lung
permeability and the filling pressure of the left ventricle.
Although conventionally lung ultrasound (LUS) pri-
marily focuses on the evaluation of faithful anatomic im-
ages of pleural effusion, pleural masses, and lung
consolidations, this technique is increasingly used for ELW
assessment through the analysis of B-line artifacts. The
definitions and nomenclature of B lines have transformed
over time. “Comet tail” sign, ultrasound lung comets, and
B lines are used interchangeably in the literature to define
the same physical artifacts.20 According to an international
consensus conference, B lines are discrete laser-like vertical
hyperechoic reverberation artifacts that arise from the
pleural line, extend to the bottom of the screen without
fading, and move in tandem with lung sliding.21
This “comet-like” sign was initially described in 1982
in relation to an intrahepatic shotgun pellet, which pro-
duced a vertical artifact with a narrow base that spread up
to the edge of the screen.22 Later, it also was observed at
AJKD Vol 71 | Iss 3 | March 2018
the lung surface, but it was not until 1997 when Lich-
tenstein et al23 first posited the potential use of this artifact
as a diagnostic marker for alveolar-interstitial syndrome. In
2004, Jambrik et al24 introduced this technique in cardi-
ology; it took 5 more years before Noble et al25 reported a
reduction in the number of B lines following dialysis, thus
setting the stage for the use of LUS in nephrology.
Although intensive research (computed tomography
and thermodilution) has supported a direct relationship
between B lines and ELW, the exact nature of this patho-
logic LUS image is not entirely known. In the initial work
by Lichtenstein et al,23 the origin of the B lines was
considered to be the thickened subpleural interlobular
septa (a low-impedance structure bounded on all sides by
air with a high acoustic mismatch), which would reflect
the ultrasound beam, giving birth to these comet-like ar-
tifacts. This concept was certified by the tomo-
densitometric correlations showing that the thickened
subpleural interlobular septa and/or ground-glass areas
were associated with the presence of the B-line arti-
facts.23,26 A different mechanism, namely resonance
among clusters of air bubbles in which the vibrating
structure is the liquid film interposed between gaseous
collections, was first proposed by Kohzaki et al.27 A well-
designed experiment by Soldati et al28,29 confirmed that B
lines are reverberations, originating most often from
volumetric variations in the relationship between the
aerated and tissue/fluid-filled parts of the lung and rarely
from the thickened interlobular septa. In line with this
hypothesis, Spinelli et al30 made a poroelastic replica of the
lung, which was able to reproduce the elastic and
morphologic lung structure as well as, in response to
ultrasound, the creation of B lines.
Although some of the published research is contradic-
tory, it seems clear that the examination can be performed
with any type of echography device and any transducer
frequency. However, visualization and the number of B
lines can be influenced by the machine settings and signal
processing.20 Sperandeo et al31 showed that the number of
B lines was higher when using a low-medium–frequency
(3.5-5.0 MHz) convex probe than with a high-frequency
(8.0-12.5 MHz) linear probe. Other authors showed no
difference on the visualization of B lines when convex,
linear, and cardiac or microconvex transducers were
used.25,26,32-34 With a linear probe, B lines are parallel,
whereas with a convex probe, they spread from the pleural
line over the screen (Fig 1). It is recommended that
penetration depth be set at 4 to 8 cm starting from the
pleural line and also that the focus of the image should be
set at the level of the pleural line (to concentrate most of
the energy for reflection and reverberating).20 The use of
harmonic (as opposed to fundamental) imaging does not
have an impact on B-line count.35
There are different approaches for assessing ELW using
LUS. In an emergency/critical care setting, a simpler
method is used. The chest is divided into 8 to 12 areas,
with 1 scan obtained for each area, and a positive
413

Figure 1. Sonographic appearance of (A) an aerated (normal) lung scan, (B, D, E) multiple B lines, and (C) confluent B lines
(arrows). Examinations were performed using a Siemens Acuson CV70 ultrasound machine with different transducers: (A-C) cardiac
P4-2, (D) linear L10-5, and (E) curved array abdominal C6-2.
ultrasound being defined as the presence of multiple (at
least 3 B lines between 2 ribs per scan area) diffuse or
bilateral artifacts.26,36-38 However, in nephrology, a more
quantitative approach is used, initially described by Jam-
brik et al.24 Briefly, both sides of the anterior and lateral
chest are scanned from the second to the fourth (on the left
side) or fifth (on the right side) intercostal spaces, at
parasternal to midaxillary lines, for a total of 28 scanning
sites. At every scanning site, the number of B lines is
recorded as a value from 0 to 10. Zero is defined as no
detectable B lines in the investigated site; at the other
extreme, a fully white screen is considered as corre-
sponding to 10 B lines.24 The sum of B lines produces a
score that quantifies the degree of ELW. New approaches,
which also assess the posterior chest, have been pro-
posed.39,40 Overall, this bedside technique is relatively
simple, with near-100% feasibility, a very short learning/
training curve,34,41-43 and high reproducibility.24,34,43-46
Comparison With Other Techniques for Fluid
Status Assessment
Overview
In the emergency department, the LUS-implemented
approach was reported to have significantly higher
414
Narrative Review
accuracy for distinguishing acute decompensated HF from
noncardiac causes of acute dyspnea compared with the
clinical workup, chest radiography alone, or natriuretic
peptide concentrations.47 According to a recent systematic
review and meta-analysis, 3 or more B lines in 2 or more
bilateral lung zones (using the simpler 8- to 12-area scan-
ning method) should be considered diagnostic for pulmo-
nary edema (sensitivity, 94%; specificity, 92%).48 For
critically ill patients with severe acute respiratory distress
syndrome, measurement of ELW by transpulmonary ther-
modilution or a transpulmonary double-indicator (thermo-
dye dilution) technique has become a standard tool in many
intensive care units because it has been shown to accurately
predict outcomes.49 Compared with transpulmonary ther-
modilution measurements, water assessment by LUS offers
very high discriminatory power for identifying moderate
and severe congestion (areas under the receiver operating
curves of 0.94 and 0.96, respectively).50
In cardiology, B lines evaluated by LUS are significantly
correlated with more established parameters of decom-
pensation (clinical congestion score, E/E0 ratio of early
diastolic mitral inflow velocity to early diastolic velocity of
the mitral annulus, and NT-proBNP concentration),
particularly when using a B-line score cutoff ≥ 15.51 A
greater number of B lines is associated with increased LV
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Narrative Review
filling pressure, as well as with larger LV end-diastolic and
end-systolic diameters, LV mass index (LVMI), left atrial
volume index, tricuspid regurgitation velocity, and esti-
mated pulmonary artery systolic pressure.52 LUS has been
reported to be a better predictor for acute pulmonary
edema hospital readmissions than other commonly used
diagnostic parameters (81% sensitivity and 78% specificity
for LUS compared with 0.74 for NT-proBNP concentra-
tion, 0.71 for New York Heart Association [NYHA]
functional class, 0.70 for clinical congestion score, and
0.69 for E/E0 ratio).53
Comparison to Other Techniques for Fluid
Status Assessment in CKD
Lung congestion, as assessed by LUS, is elevated in most
patients with CKD, regardless of whether it is symptom-
atic. Mallamaci et al34 showed that 63% of investigated
patients had moderate to severe lung congestion (≥14 B
lines). Importantly, even in asymptomatic patients, more
than half had moderate to severe lung congestion,34 the
so-called hidden threat.54,55 Other studies performed in
HD patients,40,44,45,56,57 peritoneal dialysis (PD) pa-
tients,55 or even patients with nephrotic syndrome58
yielded similar findings. In patients with CKD, 17 studies
have investigated the relationship between B lines and
other methods for fluid status assessment (Table 1).
LUS and Weight Changes (Interdialytic Weight
and Ultrafiltration Volume)
Eight studies have evaluated the relationship between LUS
and changes in interdialytic weight or ultrafiltration vol-
ume.25,44,46,56,59-62 Two studies included children
receiving PD and HD61 and also with acute kidney
injury,62 whereas the other 6 included only adults treated
by HD.25,44,46,56,59,60 Interdialytic weight gain was found
to be associated with the number of B lines in all44,59,61,62
but one59 of the studies that assessed this relationship.
Noble et al25 were the first to show that there is an asso-
ciation between ultrafiltration volume during HD and a
subsequent change in B-line number, with a decrease of
2.7 B lines for every 500 mL of volume removed. Later,
the association between volume of fluid removed and
reduction in B-line score was confirmed in other44,60 but
not all46,56 studies.
LUS and Clinical Assessment
Five studies (4 in HD34,56,57,63 and 1 in PD55) evaluated
the relationship between NYHA class and number of B
lines. As in studies performed in patients with HF, a
strong correlation between B lines and NYHA class is
observed in all these reports. However, Marino et al58
demonstrated that other important clinical signs applied
to detect and monitor fluid excess, such as peripheral
edema, do not correlate with the number of B lines in HD
patients. More recently, Torino et al64 showed that lung
crackles, in addition to peripheral edema, have low
agreement with B-line assessment in the same category of
AJKD Vol 71 | Iss 3 | March 2018
patients. In PD patients, no association between peripheral
edema and B-line score was observed.55 In patients with
active nephrotic syndrome, number of B lines has been
found to be associated with degree of pedal edema, but
only after a prolonged (60 minutes) period in a supine
position.58
The poorer association between number of B lines and
clinical signs could have several explanations. First, LUS
can only evaluate ELW, but is unable to assess the total
amount of body water of patients. Second, it is known that
these clinical methods have low sensitivity and specificity
for detecting interstitial lung edema.65 Third and most
importantly, the number of B lines increases very early in
the course of lung congestion, before the appearance of
any clinical or functional impairment, at a stage when not
even changes in blood gases or chest x-ray findings can be
observed.66
LUS and Echocardiography Assessment
Five studies have assessed the relationship between
different echocardiographic parameters and the number of
B lines.34,40,46,55,56 Of these, 4 included HD pa-
tients,34,40,46,56 whereas the remaining one was performed
in PD patients.55 Mallamaci et al34 showed for the first time
in a CKD population that B-line score is closely related to
anatomical and functional echocardiographic parameters.
Univariable correlation analysis showed significant re-
lationships between predialysis B lines and LVMI, LV
ejection fraction (LVEF), left atrial volume, early LV filling
velocity, E/E0 ratio, pulmonary pressure, and LV end-
diastolic volume. However, in multivariable regression
analysis, after including all these parameters of LV func-
tional and anatomical characteristics, only LVEF remained
associated with the number of predialysis B lines. Impor-
tantly, the strength of the association between postdialysis
B-line score and most of these parameters (LVEF, left atrial
volume, and pulmonary pressure) was unchanged.
Furthermore, it was also shown that the reduction in B-line
score was associated with predialysis LVMI, LVEF, E/E0
ratio, LV atrial volume, LV end-diastolic volume, and
pulmonary pressure.34 In contrast, 2 other studies did not
reveal a significant association between predialysis B-line
score and any of the echocardiographic parameters.40,56
Only postdialysis B-line number was found to be corre-
lated with left atrial diameter and LVEF56 or with E/E0 ,
LVEF, and pulmonary pressure.40 Furthermore, both Sir-
iopol et al56 and Weitzel et al46 were unable to confirm the
association between change in B-line score and any
echocardiographic characteristic. Such discrepancies clearly
indicate that the studied population is of prime relevance,
with LUS possibly being more relevant for obtaining
strategic information in cardiovascularly compromised HD
patients.
In the only study that included PD patients, Panuccio
et al55 showed a significant relationship between B-line
score and LVEF and left atrial volume. Moreover, in a
multivariable regression analysis that included clinical and
415
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Table 1. Characteristics of Studies Comparing Lung Ultrasound and Other Techniques for Fluid Status Assessment in Chronic Kidney Disease Patients
Correlation With
Natriuretic
Weight Clinical Ecocardiographic Peptide IVC Bioimpedance
Study Typea No. of Pts Mean Age, y Change Assessmentb Assessment Assessment Assessment Assessment
Noble et al25 Observational, 40 HD 59 Yes Yes NA NA NA NA
(2009) single center
Mallamaci et al34 Observational, 75 HD <14 B lines: 56; 14-30 B NA Yes Yes NA NA Yes
(2010) single center lines: 65; >30 B lines: 69
Panuccio et al55 Observational, 88 PD <15 B lines: 60; 15-30 B NA Yes Yes NA NA Yes
(2012) multicenter lines: 59; >30 B lines: 66
Basso et al45 Observational, 30 HD 63.8 NA NA NA Yes Yes Yes
(2013) single center
Enia et al59 Observational, 270 HD 65.9 Yes NA NA NA NA NA
(2013) multicenter
Zoccali et al57 Observational, 392 HD 65 NA Yes NA NA NA NA
(2013) multicenter
Trezzi et al44 Observational, 41 HD 62.7 Yes Yes NA NA Yes NA
(2013) single center
Siriopol et al56 Observational, 96 HD 59.1 Yes Yes Yes NA NA Yes
(2013) single center
Vitturi et al60 Observational, 71 HD 65 Yes NA NA NA Yes Yes
(2014) single center
Saad et al63 Observational, 41 HD 60.8 NA Yes NA NA NA NA
(2015) single center
Paudel et al73 Observational, 27 PD 62 NA NA NA Yes NA Yes
(2015) single center
Weitzel et al46 Observational, 20 HD 53 Yes NA Yes NA NA NA
(2015) single center
Donadio et al40 Observational, 31 HD 68.2 NA NA Yes Yes NA Yes
(2015) single center
Marino et al58 Observational, 77 (42 NS, 14 NS pts: 49; HD pts: 65 NA Yes NA NA NA NA
(2016) single center HD)
AJKD Vol 71 | Iss 3 | March 2018

Allinovi et al61 Observational, 13 (8 PD, 5 PD pts: 2c; HD pts: 4c Yes NA NA NA NA NA

(2016) single center HD)
Torino et al64 Randomized, 79 HD <5 B lines: 71; 5-14 B NA Yes NA NA NA NA

Narrative Review
(2016) multicenter lines: 74; 15-30 B lines:
71; >30 B lines: 68
Allinovi et al62 Observational, 23 (8 AKI, 9 4.7c Yes NA NA NA NA NA
(2017) single center PD, 6 HD)
Abbreviations: AKI, acute kidney injury; HD, hemodialysis; IVC, inferior vena cava; NA, not applicable; NS, nephrotic syndrome; PD, peritoneal dialysis; pt, patient.
a
All are prospective.
b
New York Heart Association class, pedal edema, or crackles.
c
Age is presented as median (years).
Narrative Review
echocardiographic characteristics, only LVEF and left atrial
volume were found to be independently associated with
B-line number.55
LUS and Natriuretic Peptides Assessment
Number of B lines was shown to have a positive rela-
tionship with natriuretic peptide values in patients without
CKD. In patients with a diagnosis of acute decompensated
HF/acute cardiogenic dyspnea, the number of B lines is
positively correlated with BNP concentrations.37,67 This
was also confirmed in patients with moderate to severe
systolic chronic HF assessed in an outpatient clinic.51
Although natriuretic peptide concentrations are related to
dialytic membranes and their use for fluid overload
assessment in ESRD continues to be debated,68 there are a
number of publications showing a direct association be-
tween these peptides and overhydration in this category of
patients.69-72 The association between B-line score and
BNP values was assessed in 3 studies, 2 in HD40,45 and 1 in
PD73 patients. Again, reports are mixed: Basso et al45
showed no significant relationship between number of B
lines and BNP values both pre- and postdialysis, whereas
Donadio et al40 observed a positive association between
these 3 variables in only the predialysis, but not post-
dialysis, setting. In the only study that included PD pa-
tients, B-line score was observed to be associated with
NT-proBNP values.73
LUS and IVC Assessment
Three trials, all in HD patients, set out to determine
whether there is an association between the IVC and B-line
score.44,45,60 Basso et al45 found that B-line score is posi-
tively associated with indexed IVC diameter (IVC diameter
divided by body surface area) in inspiration (both pre- and
postdialysis) and expiration (only predialysis) and also
with the IVC collapsibility index (only predialysis). Vitturi
et al60 observed a positive relationship between B-line
changes during dialysis and changes in both expiratory and
inspiratory IVC diameter, but not with changes in the
collapsibility index. However, these findings were not
confirmed in the study by Trezzi et al.44
LUS and BIA
There are 7 studies, 5 in HD34,40,45,56,60 and 2 in PD55,73
patients, that have examined the relationship between BIA-
derived parameters and number of B lines. All these studies
used total-body BIA, while one40 also used thoracic BIA for
fluid status assessment.40
In HD patients, the results are conflicting. Predialysis,
Mallamaci et al34 showed that there is no difference in
regard to B-line score between patients identified as
overhydrated, hypohydrated, or with normal hydration
status by BIA, though this association improved after
dialysis. On the contrary, Basso et al45 showed that B lines
are positively related to BIA-derived fluid overload and that
this association is stronger on the predialysis evaluation.
Similarly, Siriopol et al56 showed that B lines are associated
AJKD Vol 71 | Iss 3 | March 2018
with BIA-derived parameters, both predialysis (relative
fluid overload, total-body water, extracellular water, and
intracellular water) and postdialysis (relative fluid over-
load, total-body water, and intracellular water). Vitturi
et al60 also demonstrated a positive linear relationship
between residual postdialysis weight as assessed by BIA
and number of B lines. In the last study performed in HD
patients, it was shown that both total and thoracic BIA are
associated with B-line score.40 Thus, overall, it appears that
there is good agreement between BIA and LUS parameters,
with a possible confounder again being more compro-
mised LV function. Furthermore, as mentioned, LUS is not
able to properly evaluate total-body volume. In patients
with ESRD, this relationship could be even weaker because
in these patients, there is an increase in lung permeability
with a subsequent increase in ELW that is not volume
related, commonly referred to as “uremic lung.”74,75 In PD
patients, the observed results are not so conflicting. Among
those with moderate and severe lung congestion (≥15 B
lines), the proportion of BIA-overhydrated patients has
been reported to be similar to that observed in patients
with mild or no congestion (<15 B lines).55 Paudel et al73
showed that there is no significant relationship between
BIA parameters and B-line score.
Prognostic Value of LUS
Overview
LUS predicts short-term mortality and HF hospitalization
independent of atrial fibrillation status, LVEF, or timing of
the measurement during hospitalization.76 After HF hos-
pitalization, residual pulmonary congestion at discharge,
as determined by LUS, independently predicts both short-
term mortality and hospitalization for worsening HF.77-79
In one study, 3-month event-free survival for the primary
end point (all-cause death or HF hospitalization) was
found to be 27% ± 10% and 88% ± 5% in patients with 30
or more versus fewer than 30 B lines, respectively
(P < 0.0001).77 In a multivariable model, having 30 or
more B lines was found to significantly predict the com-
bined end point along with NYHA class ≥ III and IVC
diameter, whereas other indirect measures of congestion
(such as natriuretic peptides) were not retained in the
model. Of note, B-line addition to NYHA class and BNP
concentration has been reported to be associated with
improved risk classification. These data were reconfirmed
in a recent systematic review.80 In acute HF, patients with
15 or more B lines on 28-zone LUS at discharge had more
than 5-fold increased risk for HF readmission or death.
Likewise, in ambulatory patients with chronic HF, 3 or
more B lines on 5- or 8-zone LUS identified those at almost
4-fold increased risk for 6-month HF hospitalization or
death.80
Also, using LUS during regular outpatient visits of
moderate to severe systolic HF can accurately predict
hospital readmission.53 In a single-center prospective
cohort study including 97 patients, B-line number higher
417

than 30 was observed to be the strongest predictor for
acute pulmonary edema admission at 120 days (hazard
ratio [HR], 8.62; 95% confidence interval [CI], 1.8-40.1;
P = 0.006). Lack of significant pulmonary congestion
(<15 B lines) identifies a subgroup at minimal risk for
adverse outcomes.53
LUS is a useful tool for monitoring pulmonary
congestion reduction in response to treatment. In patients
with cardiogenic pulmonary edema, LUS can detect the
rapid clearance of extravascular lung water in the first 24
hours.81 In patients hospitalized for decompensated HF,
Volpicelli et al37 showed that B-line pattern is mostly
cleared after a mean of 4.2 ± 1.7 days of medical treat-
ment. Moreover, for short-term patient follow-up, ultra-
sound seems to be a more promising tool than cardiac
biomarkers.82 The same rapid change of LUS in response
to HF therapy was confirmed in a recent systematic review,
including 6 studies and 438 patients; in acute HF, B-line
number altered within as few as 3 hours of HF
treatment.80
In this context, bedside LUS was recognized as a
potentially useful way to assess pulmonary congestion by
the European Society of Cardiology in 2010. In 2015, it
was recommended in a consensus paper from the Heart
Failure Association of the European Society of Cardiology,
the European Society of Emergency Medicine, and the
Society of Academic Emergency Medicine as a first-line test
in the evaluation of suspected acute HF to assess pulmo-
nary congestion.83
Prognostic Value in CKD
We identified 6 studies that assessed the relationship be-
tween B-line score and different outcomes in patients with
CKD (Table 2).56,57,59,84-86
Enia et al investigated the relationship between B-line
number and physical function in PD84 and HD59 patients.
Both studies used the Kidney Disease Quality of Life Short
Form, a 10-question scale pertaining to self-reported
abilities to cope with the physical requirements of life,
such as attending to personal needs and walking.87 In both
studies, an increase in B-line number is associated with
poorer physical functioning independent of the severity of
HF or other risk factors.59,84
Three studies, all performed in HD populations,
assessed the relationship between B-line score and
mortality.56,57,86 Of these, one also investigated the
relationship with cardiac events57 and 2 determined
whether B-line score could improve risk prediction for all-
cause mortality57,86 or cardiac events.57 Zoccali et al57
showed that patients with very severe lung congestion
(>60 B lines) have increased risk for both all-cause mor-
tality and cardiac events, even after adjustments for clinical
and biochemical parameters (HRs of 3.04 [95% CI, 1.73-
5.35] and 3.20 [95% CI, 1.75-5.88] for all-cause mortality
and cardiac events, respectively). Our group confirmed
these findings, additionally showing that patients with a
B-line score > 30 maintained an independent association
418
Narrative Review
with all-cause mortality in a multivariate Cox model that
also included echocardiographic and bioimpedance-
derived parameters (HR, 3.63; 95% CI, 1.03-12.74).56
Importantly, a better cutoff for defining lung congestion
and its association with all-cause mortality was identified,
with patients with a B-line score ≥ 22 having increased risk
for death (HR, 2.72 [95% CI, 1.19-6.16] in the adjusted
Cox model).86
In terms of prognostic abilities, Zoccali et al57 showed
that adding B-line score to a model that included tradi-
tional and CKD-related risk factors significantly improved
the reclassification for the risk for cardiac events (10%),
but not for all-cause mortality (7.4%). It did not have an
effect on discrimination for both outcomes used in the
analysis. These results were later confirmed by Siriopol
et al,86 who showed that adding B lines to a model that
included severity of NYHA class, diabetes, high-sensitivity
C-reactive protein concentration, and LVMI did not
improve either of the prognostic abilities of this model for
predicting all-cause mortality.
Until now, there has only been one published ran-
domized trial (the BUST [Bioimpedance as a Guide for
Treatment in Hemodialysis Patients] study) that investi-
gated the utility of using LUS to guide treatment in
low-CV-risk patients treated by HD.85 There was no dif-
ference between the active and control groups in terms of a
primary composite outcome (all-cause mortality and CV
events) or secondary outcomes (all-cause mortality, CV
events, hospitalizations, or vascular access thrombosis).85
Nonetheless, the study showed an increased rate ratio for
intradialytic cramps (1.26; 95% CI, 1.16-1.37), but a
lower rate ratio for predialytic dyspnea (0.81; 95% CI,
0.68-0.96) in patients in the active group.85 However, this
study was designed to complement the ongoing
LUST (Lung Water by Ultrasound Guided Treatment
in Hemodialysis Patients; ClinicalTrials.gov identifier,
NCT02310061) trial by including patients with less severe
CV involvement.88 The LUST trial is investigating the effect
of LUS in patients with severe CV disease (a history of
myocardial infarction with or without ST elevation; un-
stable angina, acute coronary syndrome, or stable angina
pectoris; or NYHA dyspnea class III-IV) and could generate
definitive evidence about the usefulness of this technique
in HD patients.88
Limitations
It is important to underline that B lines have limited
specificity; edematous B lines cannot be readily differ-
entiated from fibrotic (dry) B lines related to interstitial
pulmonary fibrosis, as found (for example) in systemic
sclerosis.89 In this context, clinical evaluation, integration
with echocardiography, and dynamic evaluation are
suggested. Additionally, it is not possible to use B lines on
their own to distinguish between ELW accumulation due
to HF or acute respiratory distress syndrome; the latter
condition may show a more inhomogeneous and
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AJKD Vol 71 | Iss 3 | March 2018

Narrative Review
Table 2. Characteristics of Studies Analyzing the Relationship Between Lung Ultrasound–Derived B Lines and Outcomes
Study Typea No. of Pts Exclusion Criteria Type of Analysis Outcome of Interest
Enia et al84 Observational, 51 PD PD for <6 mo; peritonitis in the last 3 mo; Association Physical functioning
(2012) multicenter intercurrent acute illness; neurologic or
orthopedic disease that could interfere with
physical activity
Enia et al59 Observational, 270 HD Pts unable to complete the questionnaires; Association Physical functioning
(2013) multicenter previous amputations; neurologic or orthopedic
disease that could interfere with physical activity
Zoccali et al57 Observational, 392 HD NA Association All-cause mortality, cardiac events
(2013) multicenter prognostic
Siriopol et al56 Observational, 96 HD Age < 18 y; systemic infections and terminal Association All-cause mortality
(2013) single center neoplasia; metallic joint prostheses, cardiac
pacemakers, stents, decompensated cirrhosis,
limb amputations
Siriopol et al86 Observational, 173 HD Age < 18 y; systemic infections and terminal Association All-cause mortality
(2016) single center neoplasia; metallic joint prostheses, cardiac prognostic
pacemakers, stents, decompensated cirrhosis,
limb amputations
Siriopol et al85 Randomized, 250 HD Presence of severe cardiac failure (NYHA Intervention Main outcome: composite of all-cause mortality
(2017) multicenter classes III-IV), past myocardial infarction, stable and cardiovascular events; secondary
or unstable angina, acute coronary syndrome; outcomes: all-cause mortality, cardiovascular
metallic joint prostheses, cardiac stent or events, hospitalizations
pacemakers, decompensated cirrhosis,
pregnancy, limb amputations; known persistent
pleurisy, pulmonary fibrosis, or pneumectomy
Abbreviations: HD, hemodialysis; NA, not applicable; NYHA, New York Heart Association; PD, peritoneal dialysis; pt, patient.
a
All are prospective.
419

irregular pattern, subpleural consolidation, highly frag-
mented pleural line, and multiple B lines alternating with
spared areas.35 Moreover, subcutaneous emphysema or
morbid obesity can reduce the quality of images. Another
important limitation is that B lines cannot be used to
evaluate underhydration. Of note, it was recently
demonstrated that predialysis underhydration is associ-
ated with increased risk for death in HD patients (HR,
2.03; 95% CI, 1.32-3.12).9
Conclusions
LUS is a validated straightforward economical technique
that can be easily applied at the bedside. Its application has
significant potential in cardiology, intensive care units, and
nephrology. As has been discussed, in nephrology, its role
as a diagnostic and prognostic tool is well established, but
its clinical utility needs to be confirmed by additional
randomized trials comparing a treatment policy guided by
this technique with that using the standard approach. Re-
sults from the ongoing LUST study will complement data
from BUST and definitively provide key information about
the exact clinical value of this technique in caring for HD
patients at high CV risk.
In patients with ESRD, the differentiation between HF
and volume overload is difficult. Both can manifest with
peripheral edema, jugular venous congestion, lung
congestion, or an increase in natriuretic peptide concen-
trations. The issue becomes even more complex because
volume overload increases preload and wall stress, such
that these 2 entities can coexist in a single patient.90 We
believe that using both BIA and LUS may help in differ-
entiating these 2 entities. If there is no overhydration (as
assessed by bioimpedance) but the patient has increased
lung congestion (as assessed by LUS), this may be sug-
gestive of HF. Based on our previous findings,86 we
speculate at this time that LUS should be used in addition
to BIA for dialysis patients with significantly compromised
cardiac function, whereas BIA is probably sufficient for the
rest of patients with ESRD.
Article Information
Authors’ Full Names and Academic Degrees: Adrian Covic, MD,
PhD, Dimitrie Siriopol, MD, PhD, and Luminita Voroneanu, MD, PhD.
Authors’ Affiliations: Nephrology Department, Dialysis and Renal
Transplant Center, ‘‘Dr. C.I. Parhon’’ University Hospital, ‘‘Grigore
T. Popa’’ University of Medicine and Pharmacy, Iasi, Romania.
Address for Correspondence: Adrian Covic, MD, PhD, Nephrology
Department, Dialysis and Renal Transplant Center, ‘‘Dr. C.I. Parhon’’
University Hospital, ‘‘Grigore T. Popa’’ University of Medicine and
Pharmacy, No. 50 Carol I Blvd, Iasi, Romania. E-mail: accovic@
gmail.com
Support: None.
Financial Disclosure: Dr Covic was an honorary speaker for
Fresenius Medical Care, the manufacturer of the BCM device. Drs
Siriopol and Voroneanu declare that they have no relevant financial
interests.
420
Narrative Review
Peer Review: Received June 24, 2017 in response to an invitation
from the journal. Evaluated by 3 external peer reviewers, with
direct editorial input from an Associate Editor and a Deputy Editor.
Accepted in revised form October 12, 2017.
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