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

In landmark clinical trials, pharmacological inhibition of the renin angiot ensin system (RAS) with angiotensin-converting enzyme inhibitors (ACEIs) at tenuated the decline in renal function associated with chronic renal diseas e (CRD). Hemodynamic and nonhemodynamic effects of angiotensin TI (Ang II) attest to its central role in the pathogenesis of CRD. Angiotensin II subty pe 1 receptor antagonists (AT(1)RA) differ from ACEI in their effects on th e RAS and on bradykinin metabolism. Elevations in bradykinin levels associa ted with ACEI and stimulation of angiotensin subtype 2 receptors resulting from AT(1)RA may produce therapeutic effects unique to each class of drug. Nevertheless, in animal models of CRD, ACEI and AT(1)RA exert equivalent re noprotection, implying that their renoprotective effects result primarily f rom inhibition of Ang II-mediated stimulation of angiotensin subtype 1 rece ptors. Clinical data comparing ACEI and AT(1)RA therapy in renal disease ar e limited to short-term studies, which indicate that AT(1)RAs have equivale nt effects to ACEI on the major determinants of CRD progression, namely blo od pressure and proteinuria. AT(1)RAs were well tolerated, with side-effect profiles similar to placebo. Taken together, available evidence suggests t hat AT(1)RAs will share the renoprotective properties of ACEI in human CRD. Nevertheless, the results of long-term clinical trials are required before AT(1)RA can be recommended as an alternative to ACEI in renoprotective the rapy.