Depletion of proBNP(1-108) in Patients with Heart Failure Prevents Cross-Reactivity with Natriuretic Peptides

BACKGROUND: After synthesis by cardiomyocytes, precursor proBNP(1-108) is cleaved into NT-proBNP and BNP. Recently, cross-reactivity between these assays was discussed. The aim of this study was to characterize the cross-reactivities, through a new biochemical innovative approach consisting in the total depletion of the circulating proBNP(1-108) in patients with heart failure (HF). METHODS: This prospective study included 180 patients with chronic HF. BNP and NT-proBNP were dosed with commercial kits. ProBNP(1-108) was determined using an ELISA research assay specific to the precursor. ProBNP(1-108) depletion was performed by immunocapture with a specific antibody targeting exclusively the ProBNP(1-108) hinge region. ProBNP(1-108), BNP and NT-proBNP levels were determined before and after depletion using this process in HF patients. RESULTS: Mean age was 74.34 +/-12.5 y, and 69% of patients were males. NYHA classes II and III were the most frequent (32% and 45% respectively). Before depletion, ProBNP(1-108), NT-proBNP and BNP levels were 316.8+/-265.9 pg/ml; 6,054.0+/-11,539 pg/ml and 684.3+/-82.1 pg/ml respectively, and were closely correlated with NHYA classes. After immuno-depletion, proBNP(1-108) was decreased in mean by 96% (p<0.0001), BNP by 53% (p<0.0001) and NT-proBNP by 5%. The relationship between BNP or NT-proBNP and NHYA classes remained unchanged. CONCLUSION: Current BNP and NT-proBNP assays measured as well proBNP molecule. This cross reactivity percentage has been controversial. Thanks to the removal of circulating proBNP(1-108) with our immunodepletion process, we are now able to assess the remaining “true” BNP and NT-proBNP molecules and further evaluate their clinical relevance.