Dual blockade of the renin-angiotensin system in diabetic nephropathy

OBJECTIVE: To review the literature concerning dual blockade of the renin-angiotensin system (RAS) with an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin 11 receptor blocker (ARB) in diabetic nephrophathy. DATA SOURCES: MEDLINE (1998-September 2003), EMBASE (1998-September 2003), and International Pharmaceutical Abstracts (1998-September 2003) were used to access the literature. Search terms included angiotensin-converting enzyme inhibitor, angiotensin 11 receptor blocker, diabetic nephropathy, dual blockade, renin-angiotensin system, and combination therapy. DATA SYNTHESIS: Monotherapy with an ACE inhibitor provides incomplete blockade of the RAS. Dual blockade of the RAS has been studied in approximately 300 patients with diabetic nephropathy. Recent randomized controlled studies suggest that dual blockade using an ACE inhibitor and an ARB in diabetic nephropathy is well tolerated and will provide an additional 11-43% reduction in albuminuria versus monotherapy. CONCLUSIONS: Dual blockade of the RAS using an ACE inhibitor and an ARB provide statistically significant reductions in albuminuria and blood pressure. Use of dual blockade is safe, but requires additional monitoring for hyperkalemia. Long-term studies are needed to determine whether the decrease in albuminuria will correlate with an actual improvement from overt proteinuria to microalbuminuria or a decreased incidence of end-stage renal disease in the overall diabetic population.