Renoprotective benefits of RAS inhibition: From ACEI to angiotensin II antagonists

Renoprotective benefits of RAS inhibition: From ACEI to angiotensin II antagonists. In landmark clinical trials, pharmacological inhibition of the renin-angiotensin system (RAS) with angiotensin-converting enzyme inhibitors (ACEIs) attenuated the decline in renal function associated with chronic renal disease (CRD). Hemodynamic and nonhemodynamic effects of angiotensin II (Ang II) attest to its central role in the pathogenesis of CRD. Angiotensin II subtype 1 receptor antagonists (AT₁RA) differ from ACEI in their effects on the RAS and on bradykinin metabolism. Elevations in bradykinin levels associated with ACEI and stimulation of angiotensin subtype 2 receptors resulting from AT₁RA may produce therapeutic effects unique to each class of drug. Nevertheless, in animal models of CRD, ACEI and AT₁RA exert equivalent renoprotection, implying that their renoprotective effects result primarily from inhibition of Ang II-mediated stimulation of angiotensin subtype 1 receptors. Clinical data comparing ACEI and AT₁RA therapy in renal disease are limited to short-term studies, which indicate that AT₁RAs have equivalent effects to ACEI on the major determinants of CRD progression, namely blood pressure and proteinuria. AT₁RAs were well tolerated, with side-effect profiles similar to placebo. Taken together, available evidence suggests that AT₁RAs will share the renoprotective properties of ACEI in human CRD. Nevertheless, the results of long-term clinical trials are required before AT₁RA can be recommended as an alternative to ACEI in renoprotective therapy.