Renal effects of adenosine A(1)-receptor antagonists in congestive heart failure

Renal function is a very important prognostic indicator in patients with co ngestive heart failure. While some of the prognostic importance of poor ren al function is related to the worse physiology associated with it, there ar e suggestions that the dysfunction itself is detrimental. Recently, it has been shown that adenosine may mediate much kidney activity. In addition to vasoconstrictive and vasodilatory effects, adenosine is intrinsic to the tu buloglomerular feedback which occurs when an acute increase in sodium level s in the proximal tubule feeds back to decrease glomerular filtration. Adenosine works via both adenosine A(1) and A(2) receptors. A(1)-receptor a ntagonists decrease afferent arteriolar pressure, and increase urine flow a nd sodium excretion. Studies suggest that A(1)-receptor antagonists cause a diuretic effect not by a change in the renal haemodynamics, but by the inh ibition of water and sodium reabsorption in tubular sites secondary to dire ct tubuloglomerular feedback. Less consistent has been the occasional findi ng of increased glomerular filtration rate despite the lack of improved ren al plasma flow. Clinically important questions are: what role adenosine plays in causing th e poor renal function associated with heart failure and what A(1)-receptor antagonists do in such situations? If an A(1)-receptor antagonist could cau se diuresis while maintaining or improving glomerular filtration, it would be a useful adjunct in the treatment of severe heart failure. We evaluated the effects of the A(1)-receptor antagonist CVT-124 (BG-9719) in heart fail ure patients. CVT-124 increased sodium excretion without decreasing glomeru lar filtration rate. These data suggest that adenosine might be an importan t determinant of renal function in patients with heart failure.