Abstract 2167: An Albumin-BNP Fusion Protein Increases Natriuresis Without Compromising Renal or Left Ventricular Function in Severe Congestive Heart Failure
Background: Exogenous B-type natriuretic peptide (BNP) has been utilized to facilitate natriuresis in congestive heart failure (CHF), but recent studies suggest that BNP administration can adversely affect renal function. This study tested the hypothesis that a novel albumin-BNP fusion protein (BNPFP) construct would facilitate natriuresis without adverse effects on renal or left ventricular (LV) function in the context of severe CHF.
Methods/Results: CHF was induced in pigs (by chronic pacing at 240 bpm for 3 weeks, n=18) and 8 pigs served as reference controls. Baseline LV fractional shortening by echo (LVFS, 21±2 vs. 32±2%), renal vascular blood flow using microspheres (RenFlow, 1.73±0.09 vs. 2.23±0.26 mL/min/g), sodium clearance (NaCL, 0.43±0.11 vs. 4.35±2.45 mL/min), and fractional excretion of sodium (FENa, 0.25±0.07 vs. 0.80±0.32 %) were reduced with CHF compared to reference controls (all p<0.05). Following baseline, CHF pigs were randomized to either vehicle (VEH, n=9) or BNPFP (6 mg/kg CG77X56 [CardevaTM], i.v.; from preliminary dose ranging studies). At 30 min following infusion, NaCL increased by 492±281% with BNPFP and by 950±483% at 60 min (both p<0.05 vs. VEH). FENa at 60 min was increased by over 5-fold from baseline (p<0.05) in the BNPFP group and was higher than VEH (p<0.05, Figure⇓). This natriuretic effect was achieved without a change in RenFlow or LVFS from baseline values.
Conclusion: These unique findings demonstrated that acute infusion of an albumin BNP fusion protein construct can induce natriuresis without adversely affecting LV or renal function in the setting of CHF, and therefore hold clinical significance with respect to the use of BNP in CHF.