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 II receptor blocker (ARB) in diabetic nephrophathy.


METHODS
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 II receptor blocker, diabetic nephropathy, dual blockade, renin-angiotensin system, and combination therapy.


RESULTS
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.
Wade
Vicki L
VL
St Louis College of Pharmacy, St Louis, MO 63110-1088, USA. vwade@stlcop.edu
Gleason
Brenda L
BL
D000804:Angiotensin II / Q000502:physiology; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D012084:Renin-Angiotensin System / Q000187:drug effects*
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II