AT1 receptor blockade and renal protection

It is well known that, if there has been sufficient initial damage due to any cause, chronic renal insufficiency usually progresses, even when the original disease is no longer active. Hypertension and proteinuria are the main factors affecting chronic renal insufficiency progression. In the past years, it has been shown that ACE-inhibitors have antihypertensive and antiproteinuric capacity and can also be renoprotective partially independently to these effects. AT1 receptor antagonists (AT1RA) inhibit the renin-angiotensin system by selectively blocking the AT1 subtypes of angiotensin II receptors, without affecting, unlike ACE-inhibitors, bradykinin metabolism. Several experimental studies have confirmed that the acute renal effects of AT1RA on hemodynamics are partially different from ACE-inhibitors, because they do not dramatically reduce the resistance of the efferent arteriole. In non-hemodynamically-based animal models of renal injury, it is still unclear why AT1RA, unlike ACE-inhibitors, are partially ineffective in preserving renal morphology; in other animal models the long- term renoprotective effects of AT1RA are comparable to ACE-inhibitors. The antihypertensive and antiproteinuric effects of AT1RA have been confirmed in humans. However, the clinical impact of this new class of drugs in slowing the rate of chronic renal insufficiency progression needs to be assessed by means of prospective long-term randomized trials which are still ongoing. The hypothesis that AT1RA in association with ACE-inhibitors may allow additive renoprotection is extremely fascinating.