Tuesday, December 9, 2014

Intrarenal effects of angiotensin-converting (ACE) inhibitors and angiotensin receptor blockers (ARBs)

The manner in which renal function changes when an ACE inhibitor is started depends on the treatment circumstances. In most instances there is little to no change in serum creatinine value (or the level of renal function) when an ACE inhibitor is started. This is typically the case when hypertension alone is being treated. Occasionally, renal function declines (by 10% to 20%) shortly after an ACE inhibitor is  started, a process that arises from a resetting of renal hemodynamics and is fully reversible when the drug is discontinued.
This pattern is observed in patients with underlying renal disease. The magnitude of this early drop in renal function may, in fact, identify those patients likely to benefit most from ACE inhibitor therapy.
Concern engendered by this change in renal function is unfounded. A more substantial drop in renal function is occasionally seen in patients who are being treated with an ACE inhibitor. This occurs most commonly in patients who are either volume contracted and/or have bilateral large or small artery disease in the renal vascular bed. Correction of any volume deficit typically returns renal function to baseline values. In the
instance of renal arterial disease, reducing the dosage of an ACEinhibitor (or, if necessary, discontinuing it) will restore renal function to its baseline level. The change in renal function with ARBs given to patients with or without renal disease appears to differ little from that seen with ACE inhibitors.
In the untreated state efferent arteriolar tone is presumably increased and glomerular hyperfiltration exists (left panel). The change in the diameter of the efferent arteriole is greater with ACE inhibition, reflecting the combined effect of increased bradykinin and decreased angiotensin II concentrations on efferent arteriolar tone (middle). A proposed consequence of this change is a somewhat greater drop in the glomerular filtration rate with an ACE inhibitor. In the case of ARBs the absence of a direct effect on bradykinin limits any decrease in efferent arteriolar tone to what might occur with a reduction in angiotensin II effect (right). Although this scenario has been demonstrated experimentally, confirming evidence of this process is still not available in humans.




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