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

Stephen S. Gottlieb, D. Craig Brater, Ignatius Thomas, Edward Havranek, Robert Bourge, Steven Goldman, Farere Dyer, Miguel Gomez, Donald Bennett, Barry Ticho, Evan Beckman, William T. Abraham

Research output: Contribution to journalArticle

301 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1348-1353
Number of pages6
JournalCirculation
Volume105
Issue number11
DOIs
StatePublished - Mar 19 2002
Externally publishedYes

Fingerprint

Adenosine A1 Receptor Antagonists
Furosemide
Diuretics
Kidney
Glomerular Filtration Rate
Urine
Adenosine
Heart Failure
Diuresis
Therapeutics
Angiotensin-Converting Enzyme Inhibitors
Natriuresis
1,3-dipropyl-8-(2-(5,6-epoxy)norbornyl)xanthine
Arterioles
Treatment Failure
Cross-Over Studies
Electrolytes
Creatinine
Sodium
Placebos

Keywords

  • Adenosine antagonist
  • Congestive heart failure
  • Diuretics
  • Renal function

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

BG9719 (CVT-124), an A1 adenosine receptor antagonist, protects against the decline in renal function observed with diuretic therapy. / Gottlieb, Stephen S.; Brater, D. Craig; Thomas, Ignatius; Havranek, Edward; Bourge, Robert; Goldman, Steven; Dyer, Farere; Gomez, Miguel; Bennett, Donald; Ticho, Barry; Beckman, Evan; Abraham, William T.

In: Circulation, Vol. 105, No. 11, 19.03.2002, p. 1348-1353.

Research output: Contribution to journalArticle

Gottlieb, SS, Brater, DC, Thomas, I, Havranek, E, Bourge, R, Goldman, S, Dyer, F, Gomez, M, Bennett, D, Ticho, B, Beckman, E & Abraham, WT 2002, 'BG9719 (CVT-124), an A1 adenosine receptor antagonist, protects against the decline in renal function observed with diuretic therapy', Circulation, vol. 105, no. 11, pp. 1348-1353. https://doi.org/10.1161/hc1102.105264
Gottlieb, Stephen S. ; Brater, D. Craig ; Thomas, Ignatius ; Havranek, Edward ; Bourge, Robert ; Goldman, Steven ; Dyer, Farere ; Gomez, Miguel ; Bennett, Donald ; Ticho, Barry ; Beckman, Evan ; Abraham, William T. / BG9719 (CVT-124), an A1 adenosine receptor antagonist, protects against the decline in renal function observed with diuretic therapy. In: Circulation. 2002 ; Vol. 105, No. 11. pp. 1348-1353.
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abstract = "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.",
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T1 - BG9719 (CVT-124), an A1 adenosine receptor antagonist, protects against the decline in renal function observed with diuretic therapy

AU - Gottlieb, Stephen S.

AU - Brater, D. Craig

AU - Thomas, Ignatius

AU - Havranek, Edward

AU - Bourge, Robert

AU - Goldman, Steven

AU - Dyer, Farere

AU - Gomez, Miguel

AU - Bennett, Donald

AU - Ticho, Barry

AU - Beckman, Evan

AU - Abraham, William T.

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N2 - 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.

AB - 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.

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