Adenosine A1 receptor antagonists and the kidney

Purpose of review This review will examine the most recent evidence that adenosine receptors in the kidney can alter kidney function. Adenosine A(1)-receptors located in the afferent arteriole and proximal tubule can contribute to fluid retaining disorders by mediating tubuloglomerular feedback, afferent arteriole vasoconstriction or direct sodium absorption. In addition, A(1)-receptors may have a role for the prevention or treatment of ischemic injury to the kidney by maintaining afferent arteriole vasodilatation and preserving the glomerular filtration rate. Recent findings Animal and human studies confirm that adenosine A(1)-receptor antagonists are useful adjuvants to the treatment of congestive heart failure by increasing diuresis and natriuresis and preserving the glomerular filtration rate. These agents most likely function to directly inhibit tubular absorption of sodium, as well as inhibit tubuloglomerular feedback. There is increasing evidence that adenosine A(1)-receptors directly affect the release of renin, and that adenosine and angiotensin II act synergistically to increase renal vascular resistance and decrease renal blood flow. The ability of adenosine At-receptor antagonists to preserve the glomerular filtration rate and protect the kidney against ischemic damage or drug toxicity is not well established. Summary The utility of adenosine A(1)-receptor antagonists in the treatment of congestive heart failure should lead to larger clinical trials of these agents. There is increasing evidence that the receptors mediate vasoconstriction that is unique to the renal microcirculation. However, studies of adenosine At-receptor antagonists in animal models have largely been unsuccessful in preventing ischemic kidney damage, most likely due to the diversity of factors and events that are involved.