Dual blockade of the renin-angiotensin system in the progression of renal disease : The need for more clinical trials

• Published in: Journal of the American Society of Nephrology Vol. 17; no. 12 Suppl 3; pp. S250 - S254
• Main Authors: FERNANDEZ-JUAREZ, Gema, BARRIO, Vicente, GARCIA DE VINUESA, Soledad, GOICOECHEA, Marian, PRAGA, Manuel, LUNO, José
• Format: Conference Proceeding Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01-12-2006
• Subjects: Angiotensin II Type 1 Receptor Blockers - therapeutic use; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Associated diseases and complications; Biological and medical sciences; Blood Pressure - drug effects; Blood Pressure - physiology; Diabetes. Impaired glucose tolerance; Disease Progression; Drug Therapy, Combination; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Humans; Kidney Diseases - drug therapy; Kidney Diseases - physiopathology; Kidneys; Medical sciences; Nephrology. Urinary tract diseases; Renin-Angiotensin System - drug effects; Renin-Angiotensin System - physiology; Urinary system involvement in other diseases. Miscellaneous; Endocrinopathy; Kidney disease; Human; Nephrology; Urinary system disease; Diabetes mellitus; Urology; Prevention; Renin angiotensin system; Complication; Clinical trial; Evolution; Diabetic nephropathy; Angiotensin antagonist; ACE inhibitor
• ISSN: 1046-6673; 1533-3450
• DOI: 10.1681/ASN.2006080922

There is clear evidence that pharmacologic blockade of the renin-angiotensin system (RAS) with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) reduces proteinuria and slows the progression of renal disease in diabetic and nondiabetic nephropathies, a beneficial effect that is not related to BP control. Some patients exhibit a significant beneficial response, whereas others do not. The absence of response may be explained by the incomplete blockade of the RAS obtained with ACEI. In the search of new alternatives that could improve the antiproteinuric and nephroprotective effects of RAS blockers, the association of ACEI and ARB might prove useful. ARB produces a complete blockade of the RAS. Several studies have shown a more marked antiproteinuric effect of the dual blockade of the RAS versus ACEI or ARB alone. A recent study also demonstrated that this more marked antiproteinuric effect is associated with less progression of renal disease in primary nondiabetic nephropathies despite a similar effect on BP. Until now, there has not been any reference to a beneficial effect on progression of the dual blockade in type 2 diabetic nephropathy, which is the most frequent cause of ESRD. A multicenter, prospective, open, active-controlled, and parallel-group trial was designed to compare the effects of an ACE inhibitor versus an ARB or its combination on renal disease progression, proteinuria, and cardiovascular events in type 2 diabetic nephropathy.