Angiotensin receptor blockers in chronic renal disease: the promise of a bright clinical future

Abstract

Pharmacologic interruption of the renin-angiotensin system (RAS) with angiotensin-converting enzyme inhibitors (ACEI) is considered a standard therapeutic intervention for patients with chronic renal disease, regardless of whether systemic hypertension is present. The advent of orally active angiotensin receptor blockers (ARB) increases the number of therapeutic options for inhibiting the RAS in patients with chronic renal diseases. Clinical studies of ARB that can be compared with large-scale ACEI clinical trials have yet to be completed. More than a dozen experimental studies comparing ARB with ACEI suggest that the two classes of drugs share similar renoprotective properties. Like ACEI, ARB are effective antihypertensive and antiproteinuric agents, which greatly reduce glomerular and tubulointerstitial scarring. Although both reduce stimulation of the AT1 receptor, ARB lack the kinin-potentiating effects of ACEI. ARB may exert antifibrotic actions via the AT2 receptor, through increased levels of angiotensin II resulting from AT1 receptor blockade. Despite these pharmacologic distinctions, recent studies have not detected differences in renoprotection between ARB and ACEI. In the context of RAS inhibition, the magnitude of antihypertensive and antiproteinuric effects achieved appears to be the major determinant of renoprotection, not the class of drug used. Thus, experimental data suggest that ARB will fulfill their promise as effective agents to be used as mainstays in multifaceted clinical strategies designed to slow or arrest the progression of chronic renal disease. Confirmation of this view awaits the results of clinical trials.