CORRESPONDENCE: LETTER TO THE EDITOR
Reply
James L. Januzzi, MD, FACC*,
Donald M. Lloyd-Jones, MD, ScM, FACC and
Saif Anwaruddin, MD
* Massachusetts General Hospital, Cardiology/Internal Medicine, Yawkey 5984, 55 Fruit Street, Boston, Massachusetts 02114 (Email: jjanuzzi{at}partners.org).
Lamb and colleagues attempt to compare the results of our study to their previously published (1) data, derived from a small cohort of nondyspneic subjects (the vast majority of whom did not have heart failure [HF]). These comparisons are uninformative, and the more appropriate approach would be to examine our data in the context of the currently available data examining the utility of B-type natriuretic peptide (BNP) in the breathless patient (with and without HF) (2).
In our study, the area under the receiver operating characteristic curve (AUC) for amino-terminal pro-B-type natriuretic peptide (NT-proBNP) for diagnosis of acute HF in those with moderate or worse chronic kidney disease (CKD) was 0.88, comparable to the data from such patients in the Breathing Not Properly Multinational Study renal analysis (AUC between 0.81 and 0.86) (2). It is of great interest to us that specificity for BNP in those with CKD was not reported (2); however, with such similar AUC, there is little chance that the specificity of BNP in those with CKD is any different than demonstrated for NT-proBNP in our study. We point out that the specificity of NT-proBNP >1200 pg/ml for acute HF in patients with CKD was 72%, comparing favorably to the overall specificity of 76% reported among all subjects in the Breathing Not Properly Multinational Study of BNP (3). As well, NT-proBNP <300 pg/ml had 100% negative predictive value in patients with CKD in our study, and concentrations of NT-proBNP were also strongly prognostic in those with CKD.
Thus, although correlations between renal function and BNP or NT-proBNP may differ, at optimal cut-points it would be rather hard to argue that a clinically meaningful difference between BNP and NT-proBNP exists in those with CKD, and the assertion by Lamb and colleagues that NT-proBNP has "unacceptable performance" in the patient with CKD is not accurate.
Lamb and colleagues quite incorrectly suggest that we asserted NT-proBNP testing to be "unaffected" by renal function. We emphasized the effects of renal function on NT-proBNP, but concluded "even in the presence of impaired renal function, NT-proBNP measurement is a valuable tool for the diagnostic and prognostic evaluation of dyspneic patients," a conclusion supported by our data.
Whereas observational studies demonstrate that CKD leads to elevations in both BNP and NT-proBNP (with modest differences with respect to the magnitude of elevation of each), it is dangerous to necessarily ascribe such phenomena entirely to differential dependence on renal clearance. Indeed, early mechanistic studies of renal function and natriuretic peptides suggest the kidneys clear both markers equally (and at only 20%) (4).
The interaction between natriuretic peptides and CKD is a complex one; we concede the potential for difficulties in interpretation of NT-proBNP concentrations in those with impaired kidney function, but we strenuously emphasize that this is a circumstance that also hinders use of BNP (5). In summary, the available data do not support a clinically meaningful difference between NT-proBNP and BNP in those with CKD, and the data contradict the tacit suggestion by Lamb and colleagues that BNP is superior to NT-proBNP in those with impaired renal function.
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References
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1. Vickery S, Price CP, John RI, et al. B-type natriuretic peptide (BNP) and amino-terminal proBNP in patients with CKDrelationship to renal function and left ventricular hypertrophy. Am J Kidney Dis 2005;46:610-620.[CrossRef][Web of Science][Medline]2. McCullough PA, Duc P, Omland T, et al. B-type natriuretic peptide and renal function in the diagnosis of heart failurean analysis from the Breathing Not Properly Multinational Study. Am J Kidney Dis 2003;41:571-579.[CrossRef][Web of Science][Medline] 3. Maisel AS, Krishnaswamy P, Nowak RM, et al. Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure N Engl J Med 2002;347:161-167.[Abstract/Free Full Text] 4. Schou M, Dalsgaard MK, Clemmesen O, et al. Kidneys extract BNP and NT-proBNP in healthy young men J Appl Physiol 2005;99:1676-1680.[Abstract/Free Full Text] 5. Mueller C, Laule-Kilian K, Scholer A, et al. B-type natriuretic peptide for acute dyspnea in patients with kidney diseaseinsights from a randomized comparison. Kidney Int 2005;67:278-284.[CrossRef][Web of Science][Medline]
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