Response to Letter Regarding Article, “Urinary N-terminal Prohormone Brain Natriuretic Peptide Excretion in Patients With Chronic Heart Failure”
We appreciate the valuable comments by Van Kimmenade and colleagues on our recent article.1 In our study we observed a low urinary excretion of N-terminal prohormone brain natriuretic peptide (NT-proBNP) in patients with chronic heart failure (CHF) in comparison with healthy control individuals. We agree that the total amount of this peptide that we measured in 24-h urine collections from CHF patients is extremely low.
As Van Kimmenade and colleagues pointed out in their comment, the actual amount of NT-proBNP, a small-molecular-weight protein that is found in urine, is determined by several circulatory and renal processes comprising plasma concentration, renal blood flow, glomerular filtration fraction, tubular processes (catabolization, secretion, and reabsorption), and degradation in urine. However, the exact contribution of each step in the clearance of NT-proBNP is still unknown. Furthermore, extrarenal clearance contributes substantially to the total body clearance of NT-proBNP.2 As van Kimmenade and colleagues pointed out, tubular damage seems to play a role in the altered handling of NT-proBNP as well.
Recently, we demonstrated that tubular damage was indeed present in CHF.3 We indicated that the altered tubular handling of NT-proBNP, related to impaired renal perfusion in heart failure, is an important and probably a predominant factor in explaining the net low excretion of NT-proBNP. Therefore, we fully agree that the diagnostic and prognostic value of urine levels of NT-proBNP in CHF should be interpreted with caution. We expect that the combined information from plasma and urinary levels of NT-proBNP and tubular damage markers (eg, neutrophil gelactinase–associated lipocalin) may augment prognostication in CHF.
In general, the natriuretic peptide system provides a compensatory mechanism to the overactivated renin-angiotensin-aldosterone system in patients with heart failure. The reduced excretion of NT-proBNP in CHF may signal an important step in the maintenance of high circulatory levels as a protective mechanism.