Renal Effects of Conivaptan, Furosemide and the Combination in Patients With Heart Failure

Background: Furosemide (F) produces a sodium and water diuresis, but often at the expense of acute adverse effects on hemodynamics, glomerular filtration rate (GFR) and renal blood flow (RBF). Vasopressin V2 antagonists produce a water diuresis and are neutral to renal function. This study examined the effects of the nonselective V1a/V2 antagonist conivaptan (C) on GFR, RBF, urinary volume (UV) and urinary sodium (UNa) excretion alone, in comparison to F, and in combination with F in 8 patients with chronic stable HF. Methods: 8 patients (all male, mean age 51) with a history of stable HF and low EF were studied on 3 occasions at one week intervals. Heart rate (HR), mean arterial pressure (MAP), systemic vascular resistance and cardiac output – the latter two using impedance methodology – as well as GFR (iothalmate clearance), RBF (PAH clearance), sodium and water excretion were measured hourly for 4 hours following 20 mg + 1 mg/hr infusion C, intravenous F (dose equal to the patient's total daily dose, mean 80 mg) or the combination. Results: There were no significant differences in control hemodynamic or renal variables on the 3 study days. There were no changes from control in any hemodynamic variable at any time on any day. There was a nonsignificant decrease in GRF at 1 hour after F (76 + /− 10 SEM to 60 + /− 14 cc/hr) but not after C or the combination. Maximum increases in UV and UNa excretion occurred at 1 hour on each day: UV: F: .9 + /−.08 l/hour, C: .7 + /− .07 l/hour, F + C: 1.6 + /− .1/hour, p < .001 compared to F and C alone. UNa excretion: no change with C. After F UNa excretion increased to 80 + /− 10 meq/hour, and after F + C UNa excretion increased to 116 + /− 11 meq/hr, p < .001 vs F or C alone. Conclusion: C amplifies the natriuretic and diuretic effects of F, without adversely affecting GFR, RBF, or hemodynamics. C could therefore be useful as a F-sparing agent when significant diuresis is required.