N-Terminal Pro-Brain Natriuretic Peptide from Fresh Urine for the Biochemical Detection of Heart Failure and Left Ventricular Dysfunction

AIMS: Plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) is a strong biochemical marker of heart failure and left ventricular dysfunction (LVD). Due to renal arterio-venous clearance of NT-proBNP and the correlation of plasma concentrations with renal function, we hypothesized that NT-proBNP may have potential as a urinary marker. The objective of this study was to assess urinary concentrations of NT-proBNP and to identify the predictive value of urinary NT-proBNP for detecting LVD and heart failure. METHODS AND RESULTS: N-terminal pro-brain natriuretic peptide (Elecsys proBNP((R)), Roche) was assessed simultaneously in fresh spot urine and plasma from 191 individuals. In patients with heart failure (n = 149), urinary and plasma NT-proBNP concentrations were positively correlated (r = 0.79, P < 0.001), but urinary NT-proBNP was significantly lower than plasma NT-proBNP (42 +/- 25 vs. 1389 +/- 325 pg/mL, P < 0.001). Upon receiver operating curve analysis, urinary NT-proBNP detected LV dysfunction (ejection fraction <40%) with a sensitivity of 91% and a specificity of 98% at a cutpoint of 22 pg/mL [area under the curves (AUC) 0.98]. At the same cutpoint, symptomatic heart failure (NYHA-class > 2) was detected with a sensitivity of 97% and specificity of 98% (AUC 0.99) and clinical signs of fluid retention were detected with a sensitivity and specificity of 98% each (AUC 0.99). CONCLUSION: N-terminal pro-brain natriuretic peptide concentrations were markedly lower in the urine than in the plasma. However, urinary NT-proBNP levels increased stepwise with the severity of heart failure and LVD, and therefore yielded satisfactory predictive values for the detection of significant LVD and symptomatic heart failure. Measurement of urinary NT-proBNP is a novel, promising, and simple method for the biochemical detection of heart failure.