Renal Function, Congestive
Heart Failure, and Amino-Terminal
Pro-Brain Natriuretic Peptide Measurement
Results From the ProBNP Investigation of
Dyspnea in the Emergency Department (PRIDE) Study
Saif Anwaruddin, MD,* Donald M. Lloyd-Jones, MD, SCM, FACC,† Aaron Baggish, MD,*
Annabel Chen, MD,* Daniel Krauser, MD,* Roderick Tung, MD,* Claudia Chae, MD, MPH, FACC,*
James L. Januzzi, JR, MD, FACC*
Boston, Massachusetts; and Chicago, Illinois
We sought to examine the interaction between renal function and amino-terminal pro-brain
natriuretic peptide (NT-proBNP) levels.
The effects of renal insufficiency on NT-proBNP among patients with and without acute
congestive heart failure (CHF) are controversial. We examined the effects of kidney disease
on NT-proBNP–based CHF diagnosis and prognosis.
A total of 599 dyspneic patients with glomerular filtration rates (GFRs) as low as 14.8 ml/min
were analyzed. We used multivariate logistic regression to examine covariates associated with
NT-proBNP results and linear regression analysis to analyze associations between NT-proBNP
and GFR. Receiver-operating characteristic analysis determined the sensitivity and specificity of
NT-proBNP for CHF diagnosis. We also assessed 60-day mortality rates as a function of
Glomerular filtration rates ranged from 15 ml/min/1.73 m2to 252 ml/min/1.73m2. Renal
insufficiency was associated with risk factors for CHF, and patients with renal insufficiency were
more likely to have CHF (all p ? 0.003). Worse renal function was accompanied by cardiac
structural and functional abnormalities on echocardiography. We found that NT-proBNP and
pg/ml for patients ages ?50 years and ?900 pg/ml for patients ?50 years had a sensitivity of 85%
and a specificity of 88% for diagnosing acute CHF among subjects with GFR ?60 ml/min/1.73
m2. Using a cut point of 1,200 pg/ml for subjects with GFR ?60 ml/min/1.73 m2, we found
sensitivity and specificity to be 89% and 72%, respectively. We found that NT-proBNP was the
strongest overall independent risk factor for 60-day mortality (hazard ratio 1.57; 95% confidence
interval 1.2 to 2.0; p ? 0.0004) and remained so even in those with GFR ?60 ml/min/1.73 m2
(hazard ratio 1.61; 95% confidence interval 1.14 to 2.26; p ? 0.006).
CONCLUSIONS The use of NT-proBNP testing is valuable for the evaluation of the dyspneic patient with
suspected CHF, irrespective of renal function.
by the American College of Cardiology Foundation
(J Am Coll Cardiol 2006;47:91–7) © 2006
Testing for amino-terminal pro-brain natriuretic peptide
(NT-proBNP) is valuable for the assessment of dyspneic
patients presenting to the emergency department (ED) with
suspected acute congestive heart failure (CHF) (1–3).
When testing a dyspneic patient with NT-proBNP or the
related B-type natriuretic peptide (BNP), important con-
siderations are necessary, including knowledge of the pa-
tient’s renal function. Chronic kidney disease (CKD) is
highly prevalent among patients with CHF; conversely,
many of the same factors that place an individual at risk for
CHF can have similarly detrimental effects on renal func-
tion. This intersection between cardiac and renal insuffi-
ciencies—the so-called “cardio-renal” interaction (4–8)—is
associated with increased rates of morbidity and mortality in
patients so afflicted (5,6,8–15). It is not surprising therefore,
that CKD affects the concentrations of both NT-proBNP
and BNP; however, it is not yet clear whether this effect
reflects the increased release of the markers due to the
presence of cardiac disease in patients with CKD or due to
reductions in their clearance, as both markers may have a
degree of dependence on renal function for their removal
from circulation (16–20).
Although the effect of declining renal function on BNP
has been examined previously (17,18), less is understood
regarding the effects of renal function on NT-proBNP levels
in patients both with and without CHF, and it has been
suggested the accuracy of NT-proBNP may be more vul-
nerable than BNP to abnormalities in renal function (21).
Accordingly, we undertook the present analysis of partici-
From the *Department of Medicine, Massachusetts General Hospital and Harvard
Medical School, Boston, Massachusetts; and the †Department of Preventive Medi-
cine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. The
PRIDE study was an investigator-initiated trial, supported by Roche Diagnostics
(Indianapolis, Indiana). Data collection, analysis, and interpretation, as well as
manuscript preparation, were performed by the PRIDE Study Group, Massachusetts
General Hospital, Boston, Massachusetts. Dr. Januzzi has received grant support,
speaking fees, and consulting income from Roche Diagnostics Inc., the sponsor of the
Manuscript received June 10, 2005; revised manuscript received August 4, 2005,
accepted August 9, 2005.
Journal of the American College of Cardiology
© 2006 by the American College of Cardiology Foundation
Published by Elsevier Inc.
Vol. 47, No. 1, 2006
Thus, we feel our data are applicable to the real-world
population presenting to the ED.
Conclusions. In summary, we found a significant inverse
relationship between renal function and NT-proBNP values
in dyspneic patients with and without acute CHF. We
suggest this inverse relationship between NT-proBNP and
GFR is not explainable solely on the basis of reduced
clearance and more likely reflects the presence of underlying
structural heart disease and increased plasma volume in
patients with CKD. Although the perception is that the
performance of NT-proBNP as a diagnostic marker is more
adversely affected by renal function than BNP (18,21), we
found that NT-proBNP was useful for both diagnosing or
excluding acute CHF across a wide spectrum of renal
function (with results comparable with those reported for
BNP) and that regardless of renal function maintained its
value for prognostication of short-term mortality in CHF.
We therefore conclude that at optimal cut points, even in
the presence of impaired renal function, NT-proBNP mea-
surement is a valuable tool for the diagnostic and prognostic
evaluation of dyspneic patients.
Reprint requests and correspondence: Dr. James L. Januzzi, Jr.,
Massachusetts General Hospital, Yawkey 5984, 55 Fruit Street,
Boston, Massachusetts 02114. E-mail: JJanuzzi@Partners.org.
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Anwaruddin et al.
Renal Function and Natriuretic Peptides