Abstract 1382: AlbuBNP (Cardeva), a Novel Recombinant Human B-Type Natriuretic Peptide Serum Albumin Fusion Protein Has Prolonged Renal Enhancing Properties When Compared to Human BNP.

Abstract

BACKGROUND: AlbuBNP is a novel recombinant human BNP serum albumin fusion protein which possesses a significantly longer elimination half-life compared to BNP. To date, it remains unclear if this novel protein which represents a single molecule of BNP synthesized with the carrier protein albumin can enter the post glomerular/tubular system due to the fusion of BNP to albumin and mediate renal actions. We hypothesized that this fusion protein will have potent renal actions and possess prolonged renal hemodynamic enhancing and excretory properties based upon its unique structure as compared to native BNP. METHODS: We compared the cardiorenal and humoral actions of intravenous(IV) bolus of administration of AlbuBNP (Cardeva, CoGenesys, Rockville MD) (5 mg/kg, n=7) and Human BNP (Phoenix Pharmaceutical, Belmont CA) (25 μ g/Kg, n=5) in two groups of normal anesthetized dogs. * p<0.05 RESULTS: Single IV bolus of AlbuBNP resulted in a sustained increase in plasma cGMP (5±1 to 9±2 pmol/ml*) and urinary cGMP excretion (1136±113 to 2556±417 pmol/min*), markers of the biological activity of BNP, which remained elevated at the termination of the experiment at 270 minutes. In contrast, with human BNP, both plasma and urinary cGMP peaked at 30 minutes and returned to baseline by 150 minutes. In a similar fashion, there was a sustained increase in natriuresis (39±12 to 159±38 μEq/min*), diuresis (0.2±0.1 to 1.1±0.3 ml/min*), renal blood flow (220±22 to 301±33 ml/min*), and glomerular filtration rate (34±2 to 62±13 ml/min*) with AlbuBNP while with human BNP, these renal effects peaked at 30 minutes and returned to baseline by 150 minutes. Furthermore, there was a gradual and sustained suppression of plasma aldosterone (7.8±2 to 3.6±1 ng/dL*) with AlbuBNP. Likewise, there was a more sustained reduction of cardiac filling pressures with AlbuBNP as compared to human BNP. CONCLUSION: We report for the first time that this newly developed BNP/albumin fusion protein has a more prolonged and sustained renal enhancing properties compared to human BNP. Thus, AlbuBNP (Cardeva) represents a novel long-acting renal enhancing and aldosterone suppressing drug which has therapeutic potential for the management of cardiovascular and renal diseases that should be defined in further studies.