Radioimmunoassay for N-terminal probrain natriuretic peptide in human plasma

Measurement of plasma levels of natriuretic peptides has been used to asses s left ventricular dysfunction and prognosis. Recently levels of the N-term inal peptide fragment of the precursor of brain natriuretic peptide have be en reported to be present in peripheral plasma and to be increased in chron ic heart failure patients. Our aim in this study was to develop a radioimmu noassay for N-terminal proBNP, to compare its plasma concentrations in cont rol subjects and in patients with end-stage heart failure and to define its relation to brain natriuretic peptide (BNP). A polyclonal antibody was rai sed in rabbits against human N-terminal proBNP fragment (amino acid 1-21). The plasma N-terminal proBNP concentrations were assayed directly without e xtraction. No detectable cross-reactivity existed with other natriuretic pe ptides: BNP, ANP or N-terminal proANP. The assay had a detection limit (2 S D from zero) of 9.7 pmol/L. Plasma N-terminal proBNP was 29 (13-75) (median (range)) pmol/L in the control group. There were no gender difference, mal e: 28 (13-61) vs. female 33 (13-75) pmol/L, p= NS, but there was a positive correlation to age (r=0.52, p<0.0001). In patients with end-stage heart fa ilure the median N-terminal proBNP levels were increased significantly 616 (114-2781) pmol/L (p<0.001) and in pooled data N-terminal proBNP showed a c lose correlation to BNP (r=0.96, p<0.0001). Size exclusion of plasma extrac ts indicated that proBNP (1-108) may circulate both as intact prohormone an d as split products, N-terminal proBNP(1-76) and BNP 177 - 108). Our result s support the concept that N-terminal proBNP measurement could be a valuabl e tool in the biochemical indication of increased cardiac wall stress.