Letter by van Kimmenade et al Regarding Article, “Urinary N-Terminal Prohormone Brain Natriuretic Peptide Excretion in Patients With Chronic Heart Failure”
To the Editor:
We would like to compliment Linssen and colleagues on their recent work.1 We believe, however, that some additional comment is needed regarding the interpretation of their results.
The study by Linssen et al provides unique data; however, as already acknowledged by the authors, the amount of N-terminal prohormone brain natriuretic peptide (NT-proBNP) that is measured in urine depends not only on the filtration (ie, on the level of the glomeruli) but also on the sum of tubular secretion, catabolization at the level of the tubular brush border after secretion, and degradation after release into the urine.
It is well known that small-molecular-weight proteins (defined as peptides with a molecular weight between 1 and 50 kDa) such as NT-proBNP are catabolized in the brush border of the renal tubules after resorption.2,3 This process of catabolization of small-molecular-weight proteins is usually nearly complete; thus, only a minor amount of NT-proBNP is to be expected to be released into the urine, as can be demonstrated by the authors’ own data: the mean renal plasma flow in the heart failure patients in the study by Linssen et al was 314 mL/min,4 meaning that (314×3600)/1000=1130 L plasma would be expected to be delivered to the kidneys in their study participants during a 24-h period. The median plasma NT-proBNP concentration of the study (547 pg/mL, or 547×10−12g/mL=547×10−9g/L) suggests that 547×10−9×1130=618×10−6 g NT-proBNP would be expected to arrive in the kidney during these 24 hours. Even with a maximum filtration fraction of 28%, this means that 618×10−6×0.28=173×10−6 g NT-proBNP should be found in a 24-h urine collection. However, the urinary NT-proBNP concentration reported by Linssen and colleagues was only 55 pg/mL (55×10−9 g/L). Thus, even in the context of a 24-h urine volume of 5 L, only 5×(55×10−9)/173×10−6=0.15% could be found in the urine of these patients.
Inasmuch as we have previously reported that NT-proBNP is stable in urine for more than 24 hours and at several degrees of pH,5 the data presented by Linssen et al suggest that although NT-proBNP is indeed measurable in urine (and may have diagnostic as well as prognostic meaning when detected), caution should be taken in the interpretation of urinary NT-proBNP concentrations because there seems to be a strong influence of tubular function on concentrations of NT-proBNP that should be taken into account.
Linssen GC, Damman K, Hillege HL, Navis G, van Veldhuisen DJ, Voors AA. Urinary N-terminal prohormone brain natriuretic peptide excretion in patients with chronic heart failure. Circulation. 2009; 120: 35–41.
Smilde TD, van Veldhuisen DJ, Navis G, Voors AA, Hillege HL. Drawbacks and prognostic value of formulas estimating renal function in patients with chronic heart failure and systolic dysfunction. Circulation. 2006; 114: 1572–1580.
Michielsen EC, Bakker JA, Kimmenade RR, Pinto YM, van Dieijen-Visser MP. The diagnostic value of serum and urinary NT-proBNP for heart failure. Ann Clin Biochem. 2008; 45: 389–394.