Abstract 3121: Nesiritide and the Preservation of Renal Function in Patients with Renal Dysfunction Undergoing Cardiopulmonary-Bypass Surgery: A Double Blinded Placebo Controlled Pilot Study
BACKGROUND: Renal insufficiency is associated with increased morbidity and mortality following cardiac surgery. B-type natriuretic peptide (BNP) is a cardiac hormone that enhances glomerular filtration rate (GFR) and inhibits renin. Cystatin C has been shown to be a better endogenous marker of GFR than creatinine. We hypothesize that IV infusion of human recombinant BNP, Nesiritide (NES) in patients with renal insufficiency will prevent postoperative worsening of renal function.
METHODS: We performed a double blinded placebo-controlled pilot study in patients (n=40)) with renal insufficiency preoperatively (defined by having a calculated creatinine clearance (CrCl) of < 50 ml/min determined by the Cockroft-Gault formula), undergoing cardiac surgery with cardiopulmonary bypass (CPB). Patients were randomized to placebo (n=20) or IV low dose Nesiritide (NES) (n=20) (0.005 μg/Kg/min) for 24 hours started after the induction of anesthesia and prior to CPB.
RESULTS: Patients in the placebo group had a significant worsening of renal function 24-hours after surgery with a decrease in CrCl (43± 3 to 38±3 ml/min, p<0.05) and an increase in plasma Cystatin C (1.4±0.1 to 1.6±0.1 mg/dL, p<0.05). In contrast, renal function was preserved in the NES group with no significant change in either CrCl (45± 3 to 44±3 ml/min, p>0.05) or plasma Cystatin C (1.4±0.1 to 1.4±0.1 md/dL, p>0.05) 24-hours after surgery. This preservation of renal function in the NES group was associated with an increase in plasma cGMP (6±1 to 10.4±1 pmol/ml, p<0.05) and a strong trend for the suppression of both renin and aldosterone during the 24-hour infusion period in the NES group. Four patients in the NES group had an increase in plasma Cystatin C of >0.3 mg/dL during the hospitalization compared to eight patients in the placebo group. One patient required dialysis during the hospitalization in both groups. There were no drug related serious adverse events.
CONCLUSION: This proof of concept study supports the hypothesis that perioperative administration of low dose NES preserves renal function in patients with renal insufficiency undergoing cardiac surgery. Further studies are warranted to determine if these physiologic observations can be translated into differences in patient outcomes.