Adenosine A1 antagonists and the cardiorenal syndrome.
Adenosine A1 antagonists are being developed for the treatment of renal dysfunction in patients with congestive heart failure. After early small studies prompted hope that these agents could increase urine output without worsening the glomerular filtration rate, larger studies published and presented in 2007 confirmed their beneficial impact on weight and renal function. However, in many studies the renal benefits disappear with higher doses, suggesting that specificity may be lost with higher doses of these drugs. Investigations in animals indicate that there may also be direct benefits on the myocardium and in the lung. Although studies have not shown adverse effects at optimal dosing, the widespread actions of adenosine mandate that safety be established. Ongoing studies should be able to demonstrate whether adenosine A1 antagonists can be used to improve renal function without adversely affecting patients with heart failure.
Gottlieb
Stephen S
SS
University of Maryland School of Medicine, 22 South Greene Street, Baltimore, MD 21201, USA. sgottlie@medicine.umaryland.edu