Renal function is a very important prognostic
indicator in patients with
congestive heart failure. While some of the prognostic importance of poor renal function is related to the worse physiology associated with it, there are 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 tubuloglomerular feedback which occurs when an acute increase in
sodium levels in the proximal tubule feeds back to decrease glomerular filtration.
Adenosine works via both
adenosine A1 and A2 receptors. A1-receptor antagonists decrease afferent arteriolar pressure, and increase urine flow and
sodium excretion. Studies suggest that A1-receptor antagonists cause a
diuretic effect not by a change in the renal haemodynamics, but by the inhibition of water and
sodium reabsorption in tubular sites secondary to direct tubuloglomerular feedback. Less consistent has been the occasional finding of increased glomerular filtration rate despite the lack of improved renal plasma flow. Clinically important questions are: what role
adenosine plays in causing the poor renal function associated with
heart failure and what A1-receptor antagonists do in such situations? If an A1-receptor antagonist could cause 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 A1-receptor antagonist
CVT-124 (BG-9719) in
heart failure patients.
CVT-124 increased
sodium excretion without decreasing glomerular filtration rate. These data suggest that
adenosine might be an important determinant of renal function in patients with
heart failure.