BG9719 (CVT-124), an A1 adenosine receptor antagonist, protects against the decline in renal function observed with diuretic therapy.
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.


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-microg/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.
Gottlieb
Stephen S
SS
University of Maryland School of Medicine and the D.V.A. Medical Center, Baltimore, Md, USA. sgottlie@medicine.umaryland.edu
Brater
D Craig
DC
Thomas
Ignatius
I
Havranek
Edward
E
Bourge
Robert
R
Goldman
Steven
S
Dyer
Farere
F
Gomez
Miguel
M
Bennett
Donald
D
Ticho
Barry
B
Beckman
Evan
E
Abraham
William T
WT
D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003404:Creatinine / Q000097:blood / Q000652:urine; D018592:Cross-Over Studies; D004231:Diuresis / Q000187:drug effects*; D004232:Diuretics / Q000009:adverse effects* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004338:Drug Combinations; D004573:Electrolytes / Q000652:urine; D005260:Female; D005665:Furosemide / Q000009:adverse effects* / Q000627:therapeutic use; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006333:Heart Failure / Q000188:drug therapy; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D058915:Purinergic P1 Receptor Antagonists; D012964:Sodium / Q000652:urine; D016482:Urinalysis; D014970:Xanthines / Q000097:blood / Q000627:therapeutic use*
C097280:1,3-dipropyl-8-(2-(5,6-epoxy)norbornyl)xanthine; D000806:Angiotensin-Converting Enzyme Inhibitors; D004232:Diuretics; D004338:Drug Combinations; D004573:Electrolytes; D058915:Purinergic P1 Receptor Antagonists; D014970:Xanthines; D005665:Furosemide; D012964:Sodium; D003404:Creatinine