European Heart Journal: Acute Cardiovascular Care (2021) 10, 475–483 ORIGINAL SCIENTIFIC PAPER

doi:10.1093/ehjacc/zuab022

CA125 but not NT-proBNP predicts the

presence of a congestive intrarenal venous flow
in patients with acute heart failure
Gonzalo Nún~ ez-Marı́n 1†, Rafael de la Espriella1†, Enrique Santas1,
Miguel Lorenzo1, Gema Min ~ ana 1, Eduardo Nún ~ ez1, Vicent Bodı́1,

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Miguel González3, José Luis Górriz3, Clara Bonanad1, Juan Sanchis1,2,
Antoni Bayés-Genı́s2,4,5, and Julio Nú~
nez 1,2*
1
Cardiology Department, Hospital Clı́nico Universitario de Valencia, INCLIVA, Departamento de Medicina, Universitat de València, Avda. Blasco Ibá~ nez 17, Valencia 46010,
Spain; 2CIBER in Cardiovascular Diseases (CIBERCV), Madrid, Spain; 3Nephrology Department, Hospital Clı́nico Universitario de Valencia, INCLIVA, Departamento de Medicina,
nez 17, Valencia 46010, Spain; 4Heart Institute, Hospital Universitari Germans Trias i Pujol, Carretera de Canyet, s/n, 08916 Badalona,
Universitat de València, Avda. Blasco Ibá~
Barcelona, Spain; and 5Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain

Received 1 February 2021; revised 14 March 2021; editorial decision 17 March 2021; accepted 19 March 2021; online publish-ahead-of-print 8 April 2021

Background Intrarenal venous flow (IRVF) measured by Doppler ultrasound has gained interest as a potential surrogate marker
of renal congestion and adverse outcomes in heart failure. In this work, we aimed to determine if antigen carbohy-
drate 125 (CA125) and plasma amino-terminal pro-B-type natriuretic peptide (NT-proBNP) are associated with
congestive IRVF patterns (i.e., biphasic and monophasic) in acute heart failure (AHF).
...................................................................................................................................................................................................
Methods and We prospectively enrolled a consecutive cohort of 70 patients hospitalized for AHF. Renal Doppler ultrasound was
results assessed within the first 24-h of hospital admission. The mean age of the sample was 73.5 ± 12.3 years; 47.1% were female,
and 42.9% exhibited heart failure with preserved ejection fraction. The median (interquartile range) for NT-proBNP and
CA125 were 6149 (3604–12 330) pg/mL and 64 (37–122) U/mL, respectively. The diagnostic performance of both expo-
sures for identifying congestive IRVF patterns was tested using the receiving operating curve (ROC). The cut-off for CA125
of 63.5 U/mL showed a sensibility and specificity of 67% and 74% and an area under the ROC curve of 0.71. After multi-
variate adjustment, CA125 remained non-linearly and positively associated with congestive IRVF (P-value = 0.008) and
emerged as the most important covariate explaining the variability of the model (R2: 47.5%). Under the same multivariate
setting, NT-proBNP did not show to be associated with congestive IRVF patterns (P-value = 0.847).
...................................................................................................................................................................................................
Conclusions CA125 and not NT-proBNP is a useful marker for identifying patients with AHF and congestive IRVF patterns.
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Keywords Acute heart failure • Biomarkers • CA125 • NTproBNP • Intrarrenal Doppler ultrasound • Congestion
• Cardiorenal

.. congestion phenotype and determine the adequacy and intensity of

Aims ..
.. decongestive therapies.1,3
.. In this context, intrarenal venous flow (IRVF) measured by
Congestion is a hallmark feature of worsening heart failure (HF); ..
however, its severity and organ distribution vary widely between .. Doppler ultrasound has emerged as a promising imaging tool to
.. evaluate renal congestion4–6; with discontinuous IRVF patterns (i.e.
patients.1,2 Consequently, there is a growing interest in searching for ..
instruments that may help physicians identify the predominant .. biphasic and monophasic) having been shown to predict a reduced

* Corresponding author. Tel: þ34 652856689, Fax: þ34 963862658, Email: yulnunez@gmail.com
†
These two authors contributed equally to this work.
C The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.
Published on behalf of the European Society of Cardiology. All rights reserved. V
476
..
diuretic response, worsening renal function, and adverse out-
comes.7–12 However, the assessment of IRVF in the often dyspneic
patient during the early phase of hospital admission may be challeng-
ing and time-consuming.13 Therefore, we aimed to evaluate whether
plasma antigen carbohydrate 125 (CA125) and the amino-terminal
pro-B-type natriuretic peptide (NT-proBNP), two widely available
surrogate markers of congestion,1 were associated with discontinu-
ous IRVF patterns in patients with AHF.
Methods
Study design and patient population
We prospectively included a consecutive cohort of 73 patients hospital-
ized for acute heart failure (AHF) at the Cardiology department of a ter-
tiary care teaching hospital (Hospital Clı́nico Universitario de Valencia,
Spain) from January 2020 to December 2020. Trained cardiologists per-
formed the diagnosis of AHF according to current guidelines.14 Either
patients with new-onset or decompensated chronic HF were eligible.
The main exclusion criteria were dialysis, kidney transplantation, auto-
somal dominant polycystic kidney disease, and postrenal obstruction.
Within the first 24 h of hospital admission, all patients underwent a com-
plete physical examination, blood test, transthoracic echocardiography,
and intrarenal Doppler ultrasonography (IRD). This study complies with
the Declaration of Helsinki and was approved by the local institutional re-
view committees. All patients provided written informed consent.
Procedures and measurements
Intrarenal Doppler ultrasonography study
After obtaining informed consent, an investigator not involved in the
patient’s clinical care performed the IRD at the time of echocardiography
using the same ultrasound system (EPIQ 7, Philips Healthcare) with a sec-
tor transducer frequency range of 2.5–5 MHz. IRD was recorded in the
right kidney with the patient in the left lateral decubitus position. The vel-
ocity range of the colour Doppler was set to 15 cm/s. Colour Doppler
images were used to determine interlobar vessels, and the sample volume
was set on the best-visualized colour Doppler signal. Pulsed Doppler
waveforms of vein and artery were recorded simultaneously at the end
of expiration during at least three cardiac cycles. Doppler waveforms
were divided into continuous (non-congestive) and discontinuous (con-
gestive) IRVF patterns. Discontinuous IRVF was defined as a pattern in
which velocity at the nadir was zero.8 Two types of discontinuous IRVF
were recorded: biphasic (with venous peaks during systole and diastole)
and monophasic (with a venous peak only during diastole).
Echocardiography
Comprehensive transthoracic echocardiography was performed accord-
ing to published guidelines using standard views and techniques.15,16 Left
heart parameters included left ventricular ejection fraction (LVEF), mitral
inflow velocity to averaged (medial and lateral) annular relaxation velocity
(E/e0 ), and more than moderate mitral regurgitation. Right heart parame-
ters included basal diameter of the right ventricle, tricuspid annular plane
systolic excursion, more than moderate tricuspid regurgitation (TR), in-
ferior vena cava (IVC) diameter, and the percentage of inspiratory col-
lapsibility, right atrial pressure (RAP), and systolic pulmonary arterial
pressure (SPAP). RAP (as a surrogate of CVP) was estimated based on
IVC parameters according to current recommendations.17 SPAP was
estimated by adding RAP to the peak TR systolic pressure gradient.16
G. Nú~nez-Marı́n et al.
.. Congestion assessment
.. Dyspnoea, orthopnoea, fatigue, jugular venous pressure (JVP), rales, and
..
.. pedal oedema were assessed at admission based on a standardized
.. 4-point scale ranging from 0 to 3 as described by Ambrosy et al.18 A com-
.. posite congestion score was calculated by summing the individual scores
..
.. of orthopnoea (0–3), JVP (0–3), and pedal oedema (0–3).18
..
..
.. Laboratory data
.. Blood samples were taken within the first 24 h of hospital admission. The
..
.. estimated glomerular filtration rate (eGFR) was calculated according to
.. the Chronic Kidney Disease Epidemiology Collaboration equation
..
.. (CKD-EPI). Plasma concentrations of NT-proBNP and CA125 were
.. measured with the commercially available electrochemiluminescent
.. sandwich immunoassay (Roche ElecsysV NT-proBNP assay; Roche R
..
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.. ElecsysV CA 125 assay). For NT-proBNP, the intra-assay precision (coef-
R
.. ficient of variation) is 1.2–1.5%, and the inter-assay precision (coefficient
..
.. of variation) is 4.4–5.0%, with an analytical range of 5–35 000 pg/mL.19
.. For CA125, the intra-assay precision (coefficient of variation) is 1.4–2.0%,
..
.. and the inter-assay precision (coefficient of variation) is 0.0–0.9%, with an
.. analytical range of 0.6–5000 U/mL.20
..
..
.. Reproducibility
..
.. To assess intraobserver variability, a single observer analysed data from
.. 15 examinations twice: at the moment of acquisition and 4 weeks later.
.. To test interobserver reproducibility, a single sonographer analysed data
..
.. from 15 examinations performed by the other sonographer without
.. knowing the other observer’s initial interpretation.
..
..
.. Statistical analysis
..
.. Continuous variables were expressed as mean (± standard deviation) or
.. medians [interquartile range (IQR)], as appropriate. Discrete variables
.. were summarized as percentages. Baseline characteristics among IRVF
..
.. categories (continuous vs. discontinuous IRVF patterns) were compared
.. using the Student’s t-test for continuous variables and chi-square test for
..
.. categorical variables.
.. The diagnostic performance of both exposures (CA125 and NT-
..
.. proBNP) for identifying a congestive IRVF was tested using the receiving
.. operating curve (ROC) and compared using the roccomp command. The
.. optimal cut-point (best balance between sensitivity and specificity) was
..
.. tested with the Youden method. Independent factors associated with
.. congestive IRVF were assessed by multivariate logistic regression analyses
..
.. using univariate factors with a value of P < 0.05. A final model was derived
.. by using backward stepwise selection. The linearity assumption for all
..
.. continuous variables was simultaneously tested, and the variable trans-
.. formed, if appropriate, with fractional polynomials. Covariates included in
.. the final multivariate model were blood urea nitrogen, systolic blood
..
.. pressure, pedal oedema, IVC diameter, and CA125. The covariates’ con-
.. tribution to the model’s predictability was assessed by the coefficient of
..
.. determination (R2). Intra- and interobserver reproducibility was assessed
.. as a percentage of agreeability and Cohen’s kappa statistic. All analyses
..
.. were performed using STATA 15.1 (StataCorp, 2017, Stata Statistical
.. Software: Release 15; StataCorp, LLC, College Station, TX, USA).
..
..
..
.. Results
..
..
.. Baseline characteristics
..
.. Of the 73 eligible patients, 3 patients (4.1%) were excluded because
.. of inadequate intrarenal venous Doppler images. Finally, 70 patients
..
. were enrolled and included in the analysis. The mean age of the
Congestive intrarenal venous flow in patients with AHF 477

..
sample was 74 ± 12 years, 33 (47.1%) were female, 40 (57.1%) had an
LVEF <50%, and 30 (42.9%) had a prior history of chronic kidney dis-
ease (eGFR <60 mL/min/1.73 m2). The median (IQR) of eGFR, NT-
proBNP, and CA125 at admission were 50 mL/min/1.73 m2 (33–72),
6149 pg/mL (3604–12 330), and 64 U/mL (37–122), respectively. A
total of 43 subjects (61.4%) had a discontinuous IRVF pattern at base-
line (22 biphasic and 21 monophasic). Baseline characteristics across
congestive and non-congestive IRVF patterns are summarized in
Table 1. Overall, the group of patients with congestive IRVF patterns
showed greater evidence of clinical congestion and echocardiograph-
ic features of right-sided HF. Conversely, those with non-congestive
IRVF had higher blood pressure at admission. Of note, even though
the presence of haemodynamically significant TR did not reach
.. Discussion
..
..
.. In this nonselected AHF population, we observed three major find-
.. ings. First, CA125 emerged as an independent predictor of congestive
..
.. IRVF at admission. The relationship was positive and non-linear, with
.. a stronger association in patients with CA125 plasma levels >63.5 U/
..
.. mL. Second, this Doppler-derived intrarenal haemodynamic pheno-
.. type was a prevalent finding encountered in about two-third of
..
.. patients during the first 24 h of hospital admission. Third, the contri-
..
.. bution of established surrogates of increased CVP and myocardial
.. stretch, such as IVC diameter and NT-proBNP, respectively, were
..
.. marginal or not independently associated with congestive IRVF.
..
..
.. IRVF, NTproBNP, and echo-surrogates of

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statistical significance between patients with congestive and non-
congestive IRVF patterns, the proportion of patients with more than .. increased CVP
..
moderate TR was numerically higher in the subgroup of patients with .. The potential usefulness of renal Doppler ultrasonography as a sur-
congestive IRVF patterns (especially those with monophasic IRVF, ..
.. rogate of renal congestion in HF is based on the assumption that
Supplementary material online, Table S1). .. increased renal interstitial pressure caused by elevated CVP may re-
..
.. duce renal parenchymal compliance around intrarenal venous ves-
.. sels, dampening the normal continuous flow to discontinuous
Association between CA125, NT-proBNP, ... patterns.4,5 However, there is limited available data to support this
..
and other surrogates of increased CVP .. notion in the AHF setting. To the best of our knowledge, this is the
with congestive IRVF .. first study evaluating the association between commonly used met-
..
In univariate analysis, the group of patients with congestive IRVF pat- .. rics of congestion with IRVF during the early phase of admission for
.
terns showed significantly higher median values of CA125 (107 U/mL .. AHF. In this cohort, and consistent with previous studies,7,10 congest-
.
[46–140] vs. 39 U/mL [21–78], P < 0.001), but not NTproBNP .. ive IRVF patterns were more frequently observed in patients with
.
(5755 pg/mL [3577–12 122] vs. 4582 pg/mL [2788–10 194], .. clinical and echocardiographic proxies of right-sided HF. However,
.
P = 0.264). In fact, we found a stepwise increase in CA125 values .. IVC diameter and NTproBNP as metrics of increased CVP and car-
.
when moving from normal to greater severity of renal congestion .. diac filling pressures, respectively, were not independently associated
.
(continuous, biphasic, and monophasic IVFR patterns), as is shown in .. with congestive IRVF patterns. Several reasons may explain this lack
.
Figure 1. Similarly, a positive association between CA125 and other .. of association. First, because the kidneys are encapsulated organs,
.
echo metrics of right-sided HF was also observed (Supplementary ... renal venous outflow does not depend exclusively on CVP but also
material online, Figure S1). The ROC curves of CA125 and ... on extrinsic factors that may exert extrarenal compression (e.g. asci-
NTproBNP for identifying a congestive IRVF were 0.746 vs. 0.580, re- ... tes, visceral oedema, engorgement of splanchnic circulation).21,22
spectively (P-value = 0.071). The cut-off for CA125 of 63.5 U/mL ... Second, the traditional echo-derived surrogates of right-sided filling
showed a sensitivity of 67%, a specificity of 74%, and an area under ... pressures are influenced by the severity of tricuspid regurgitation,
.
the ROC curve of 0.71 (Supplementary material online, Figure S1). .. atrial fibrillation, and myocardial compliance.17 Therefore, its pres-
.
After multivariate adjustment, CA125 remained non-linearly and .. ence does not necessarily indicate a state of systemic venous conges-
.
positively associated with a congestive IRVF pattern (Figure 2) and .. tion. Third, IRVF might become disrupted because of sympathetically
.
emerged as the most important covariate explaining the variability of .. mediated reductions in systemic and intrarenal venous capacitance ir-
.
the model (R2: 47.5%), followed by pedal oedema (positively associ- .. respective of other metrics indicative of increased cardiac filling pres-
.
ated, R2: 26.6%) and systolic blood pressure (inversely associated, R2: .. sures.23,24 Thus, discontinuous IRVF might not be an exact
.
12.1%). Table 2 shows the final multivariate model. Plots depicting the .. representation of elevated CVP, especially in the acute setting.
.
association between covariates and congestive IRVF are shown in .. Fourth, some patients presenting with the phenotype characterized
.
Figure 3. Of note, IVC diameter was not an independent determinant .. by acute redistribution of blood to the lung vasculature in the context
.
of congestive IRVF (P = 0.103). The area under the ROC curve of the .. of increased left-sided filling pressures may have elevated NT-
.
multivariate model was 0.893. Under the same multivariate setting, .. proBNP values without being truly volume overloaded. Fifth, in add-
..
NT-proBNP was not associated with a congestive IRVF (Figure 4). .. ition to its association with intravascular and intracardiac pressures,
..
.. NT-proBNP plasma levels are influenced by several other non-
.. haemodynamic factors such as age, obesity, and renal function.25
..
Reproducibility ..
Classifications of IRVF patterns were consistent between intraob- ... IRVF and CA125
server (% of agreement: 100%; kappa ¼ 1.00, P < 0.001) and inter- ... In contrast to NTproBNP and IVC diameter, CA125 was independ-
.
observer (% of agreement: 93.3%; kappa ¼ 0.90, P < 0.001) .. ently associated with congestive IRVF. Although the exact mechanism
assessments.
.. behind CA125 up-regulation in AHF is not well characterized, one
478 G. Nú~nez-Marı́n et al.

Table 1 Baseline characteristics according to intrarenal venous flow pattern

Variables All patients Non-congestive Congestive P-Value

(n 5 70) IRVF (n 5 27) IRVF (n 5 43)
....................................................................................................................................................................................................................
Demographics and medical history
Age, years 77 [67-83] 77 [67-83] 78 [67-83] 0.772
Female sex 33 (47.1) 15 (55.6) 18 (41.9) 0.264
HTA 57 (81.4) 24 (88.9) 33 (76.7) 0.203
Dyslipidaemia 45 (64.3) 17 (63.0) 28 (65.1) 0.855
DM 46 (65.7) 20 (74.1) 26 (60.5) 0.243
Obesity 26 (37.7) 11 (40.7) 15 (35.7) 0.674
Smoker 8 (11.4) 3 (11.1) 5 (11.6) 0.947
Former smoker 26 (37.7) 11 (40.7) 15 (35.7) 0.674

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Chronic kidney diseasea 30 (42.9) 12 (44.4) 18 (41.9) 0.832
CAD 18 (26) 6 (22) 12 (28) 0.596
De novo HF 34 (48.57) 16 (59.26) 18 (41.86) 0.156
HFpEF 30 (43) 13 (48) 17 (40) 0.478
NYHA previous to admission
NYHA I 32 (46) 14 (52) 18 (42) 0.414
NYHA II 32 (46) 12 (44) 20 (47) 0.866
NYHA III 6 (9) 1 (4) 5 (12) 0.249
Vital signs
SBP, mmHg 140 [122–163] 152 [132–175] 133 [118–158] 0.037
DBP, mmHg 80 [69–91] 89 [75–92] 73 [65–90] 0.024
HR, b.p.m. 82 [70–104] 83 [68–105] 82 [70–104] 1.00
Clinical presentation
NYHA on admission
NYHA II 2 (2.9) 0 (0.0) 2 (4.7) 0.256
NYHA III 34 (48.6) 11 (40.7) 23 (53.5) 0.299
NYHA IV 34 (48.6) 16 (59.3) 18 (41.9) 0.156
Rales 69 (98.6) 26 (96.3) 43 (100) 0.204
Oedema 42 (60.0) 9 (33.3) 33 (76.7) <0.001
JVP >_10 cmH2O 25 (35.7) 5 (18.5) 20 (46.5) 0.017
CCS on admission 5 [4–6] 4 [4–5] 6 [4–6] 0.082
Electrocardiogram
Atrial fibrillation 33 (47) 9 (33) 24 (56) 0.067
LBBB 14 (20) 6 (22) 8 (19) 0.713
Echocardiography
LVEF, % 42 [29–61] 46 [33–59] 35 [28–63] 0.282
Mitral E/e0 18.2 [13.9–24] 18.6 [15.8–22.2] 17.3 [13.3–25] 0.339
MR > moderate 19 (27.1) 6 (22.2) 13 (30.2) 0.463
TR > moderate 16 (22.9) 4 (14.8) 12 (27.9) 0.204
Estimated SPAP, mmHg 50 [40–62] 46 [40–50] 55 [42–66] 0.049
Basal RV diameter 39 [36–45] 37 [35–39] 42 [37–46] 0.007
TAPSE, mm 17 [15–20] 19 [16–20] 16 [14–21] 0.118
IVC diameter, mm 24 [20–27] 22 [18–24] 25 [22–28] 0.001
Collapsibility of IVC <50% 55 (78.6) 16 (59.3) 39 (90.7) 0.002
Estimated RAP
Normal (3 mmhg) 13 (18.6) 9 (33.3) 4 (9.3) 0.012
Mildly elevated (8 mmHg) 12 (17.1) 6 (22.2) 6 (13.9) 0.372
Severely elevated (15 mmHg) 45 (64.3) 12 (44.4) 33 (76.7) 0.006
Laboratory
Creatinine, mg/dL 1.28 [0.94–1.72] 1.2 [0.82–1.64] 1.31 [0.99–1.76] 0.320
eGFR, mL/min/1,73 m2 51 [33–72] 54 [33–73] 48 [33–72] 0.608
Urea, mg/dL 54 [40–82] 48 [39–61] 61[40–93] 0.115
Continued
Congestive intrarenal venous flow in patients with AHF 479

Table 1 Continued

Variables All patients Non-congestive Congestive P-Value

(n 5 70) IRVF (n 5 27) IRVF (n 5 43)
....................................................................................................................................................................................................................
Sodium, mEq 141 [138–143] 141 [138–144] 141 [138–143] 0.442
Potassium, mEq 4.0 [3.5–4.4] 3.9 [3.4–4.4] 4.0 [3.5–4.4] 0.515
Haemoglobin, mg/dL 12.3 [10.8–13.3] 12.6 [11.3–13.5] 12.1 [10.5–13.2] 0.294
Haematocrit, % 39 [34–43] 40 [34–44] 39 [33–43] 0.359
NTproBNP, pg/mL 5018 [3160–10673] 4582 [2788–10194] 5755 [3577–12122] 0.264
CA125, U/mL 64 [37–122] 39 [21–78] 107 [46–140] <0.001

Data are expressed as number (%) or median [interquartile range] as appropriate.

CA125, antigen carbohydrate 125; CAD, coronary artery disease; CCS, composite congestion score; DBP, diastolic blood pressure, DM, diabetes mellitus; eGFR, estimated
glomerular filtration rate; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HR, heart rate; HTA, hypertension; IRVF: intrarenal venous flow; LBBB, left

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bundle branch block, LVEF, left ventricular ejection fraction; NYHA, New York Heart Association; MR, mitral regurgitation; RAP, right atrial pressure; RV, right ventricle; SBP,
systolic blood pressure; SPAP, systolic pulmonary arterial pressure; TAPSE, tricuspid annular plane systolic excursion; TR, tricuspid regurgitation.
a
Chronic kidney disease was defined as eGFR <60 mL/min/1.73 m2 using creatinine obtained at the latest available outpatient visit prior to admission and assessed during a stable
phase of the disease.

Figure 1 Antigen carbohydrate 125 values according to intrarenal venous flow patterns. Values are expressed as median (interquartile range).

..
hypothesis is that elevated hydrostatic pressure and inflammatory ..
cytokines in the setting of congestion activate mesothelial cells in se- ..
..
rosal surfaces leading to CA125 overproduction and release.26 In ..
fact, plasma levels of this glycoprotein are elevated in almost two- ..
..
third of patients with AHF27 and are positively correlated to proxies ..
of right-sided HF25 and to the intensity of congestion.28 The present ..
..
study adds new evidence to this field by showing that CA125 ..
emerged as the most important predictor of congestive IRVF,
accounting for roughly 47.5% of the model variability. Our clinical
observations raise the hypothesis that CA125 might be capturing
two crucial mechanisms involved in renal venous hypertension and,
thus, in the development of discontinuous IRVF patterns (Figure 5): (i)
increased intravascular hydrostatic pressures in the setting of
systemic venous congestion and (ii) elevated intra-abdominal pres-
sure secondary to visceral oedema and subclinical ascites.21,29
Clinical implications
Beyond its biological plausibility, present findings have relevant
clinical implications. First, elevated CA125 levels at admission may
.. help identify a subgroup of patients with a higher probability of
..
.. renal congestion. Therefore, and considering that renal venous
.. pressure (RVP) is a major determinant of renal blood flow (renal
..
.. perfusion pressure [mean arterial pressure - RVP]/renal vascular
.. resistance), higher CA125 may be useful to identify patients who
..
. benefit from a more aggressive diuretic strategy.28 Indeed, current
480 G. Nú~nez-Marı́n et al.

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Figure 2 Antigen carbohydrate 125 and congestive intrarenal venous flow. Functional form.

.. Limitations
Table 2 Multivariate logistic regression analyses for ..
.. Several limitations need to be acknowledged. First, this study has
predictors of congestive intrarenal venous flow pattern ..
patterns .. the inherent limitations of being a single-center observational
.. study. Second, due to the limited sample size, some of the nega-
Variables odds ratio (OR) (95% confidence P- ..
.. tive results could be explained by type II error (insufficient statis-
interval (CI)) Value
................................................................................................. .. tical power). This issue also precludes confidently evaluating the
..
BUN, mg/dL 3.21 (0.71–14.39) 0.127 .. contribution of other clinical/echocardiographic proxies of right-
.. sided HF to predict a congestive IRVF pattern. Third, we included
SBP, mmHg 0.97 (0.94–0.99) 0.019 ..
Pedal oedema 5.31 (1.26–22.34) 0.022 .. only patients with AHF, so our conclusions do not apply to
..
IVC diameter, mm 1.00 (0.99–1.00) 0.103 .. patients with stable chronic HF. Fourth, we did not perform an in-
CA125, U/mL 1.39 (1.08–1.77) 0.008 .. vasive haemodynamic assessment, so we cannot establish direct
..
.. correlations between IRVF patterns and invasive right-sided filling
BUN, blood urea nitrogen; CA125, antigen carbohydrate 125; IVC, inferior vena .. pressures. Fifth, we did not measure intra-abdominal pressure dir-
cava; SBP, systolic blood pressure. ..
.. ectly, so its potential contribution is merely speculative. Sixth, al-
..
.. though experienced sonographers performed all the IRD studies
findings may be interpreted as proof of concept explaining the
.. and echocardiograms, they did not evaluate the same patient
..
results of a recent randomized clinical trial endorsing the utility of .. twice at the same time point. Thus, imaging acquisition reliability
.. was not assessed. Finally, IRD studies were not reviewed by an in-
CA125 for tailoring the intensity of diuretic therapy in patients ..
with AHF and renal dysfunction on admission.28 Second, the .. dependent core laboratory.
..
observed cut-off point of 63.5 U/mL for identifying congestive ..
IRVF patterns is closely related to the cut-point associated with an ..
..
increased risk of 6-month mortality.30 Third, although point-of- .. Conclusions
care ultrasound applications are emerging as promising tools for ..
..
phenotyping and monitoring HF patients, there are still logistic .. In patients with AHF, CA125 rather than NTproBNP is a useful bio-
limitations that preclude its widespread use in daily clinical prac- .. marker for identifying congestive IRVF patterns. Further studies
..
tice. Conversely, CA125 is widely available and low cost and has .. should focus on establishing well-validated risk factors (and potential-
an independent predictive ability beyond clinical and biochemical .. ly risk scores) for identifying patients at risk of ‘congestive nephrop-
..
markers of congestion (including natriuretic peptides).26 .. athy’ in whom IRVF assessment might be recommended.
..
Congestive intrarenal venous flow in patients with AHF 481

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Figure 3 Functional form of the association between (a) inferior vena cava diameter, (b) systolic blood pressure, and (c) blood urea nitrogen and
congestive intrarenal venous flow.

Figure 4 Amino-terminal pro-B-type natriuretic peptide and congestive intrarenal venous flow. Functional form.
482 G. Nú~nez-Marı́n et al.

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Figure 5 Graphical scheme of the proposed mechanisms behind the association between antigen carbohydrate 125 and congestive intrarenal
venous flow.

..
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