Published online before print February 25, 2002, doi: 10.1161/hc1102.105264
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(Circulation. 2002;105:1348.)
© 2002 American Heart Association, Inc.
Clinical Investigation and Reports |
BG9719 (CVT-124), an A1 Adenosine Receptor Antagonist, Protects Against the Decline in Renal Function Observed With Diuretic Therapy
From the University of Maryland School of Medicine and the D.V.A. Medical Center (S.S.G.), Baltimore, Md; Indiana School of Medicine (D.C.B.), Indianapolis, Ind; Medical Research Institute (I.T.), Slidell, La; Denver Health Medical Center (E.H.), Denver, Colo; University of Alabama (R.B.), Birmingham, Ala; Tucson VAMC, SAVAHCS, University of Arizona (S.G.), Tucson, Ariz; New Orleans Clinical Trials Management (F.D., M.G.), Covington, La; Biogen Inc (D.B., B.T., E.B.), Cambridge, Mass; and University of Cincinnati College of Medicine (W.T.A.), Cincinnati, Ohio. Dr Abraham is now at University of Kentucky College of Medicine, Lexington, Ky.
Correspondence to Stephen S. Gottlieb, MD, Division of Cardiology, University of Maryland School of Medicine, 22 South Greene St, Baltimore, MD 21201. E-mail sgottlie{at}medicine.umaryland.edu
Background— Adenosine may adversely affect renal function via its effects on renal arterioles and tubuloglomerular feedback, but effects of adenosine blockade in humans receiving furosemide and ACE inhibitors is unknown.
Methods and Results— This was a randomized, double-blind, ascending-dose, crossover study evaluating 3 doses of BG9719 in 63 patients with congestive heart failure. Patients received placebo or 1 of 3 doses of BG9719 on 1 day and the same medication plus furosemide on a separate day. Renal function and electrolyte and water excretion were assessed. BG9719 alone caused an increase in urine output and sodium excretion (P<0.05). Although administration of furosemide alone caused a large diuresis, addition of BG9719 to furosemide increased diuresis, which was significant at the 0.75-µg/mL concentration. BG9719 alone improved glomerular filtration rate (GFR) at the 2 lower doses. Furosemide alone caused a decline in GFR. When BG9719 was added to furosemide, however, creatinine clearance remained at baseline at the 2 lower doses.
Conclusions— In patients with congestive heart failure on standard therapy, including ACE inhibitors, BG9719 increased both urine output and GFR. In these same patients, furosemide increased urine output at the expense of decreased GFR. When BG9719 was given in addition to furosemide, urine volume additionally increased and there was no deterioration in GFR. A1 adenosine antagonism might preserve renal function while simultaneously promoting natriuresis during treatment for heart failure.
Key Words: adenosine antagonist • renal function • congestive heart failure • diuretics
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