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Beyond Blood Pressure Control: Targeting Proteinuria with Renin-Angiotensin-Aldosterone Inhibitors

A combination of aliskiren and losartan reduced albuminuria in patients with type 2 diabetes and nephropathy — at least in the short term.

Aliskiren is an oral renin inhibitor recently approved for marketing in the U.S. In the Aliskiren in the Evaluation of Proteinuria in Diabetes (AVOID) trial, a double-blind, randomized, placebo-controlled study sponsored by the manufacturer of aliskiren, investigators explored whether combining aliskiren with losartan, an angiotensin-receptor blocker, would be renoprotective in patients with type 2 diabetes. After a 3-month, open-label run-in period, patients with type 2 diabetes, hypertension, and proteinuria who were receiving losartan (with or without other antihypertensive agents that do not block the renin-angiotensin-aldosterone system) were assigned to receive additional aliskiren (150 mg/day for 3 months, 300 mg/day thereafter) or placebo for 6 months. The primary outcome of interest was reduction of albuminuria.

Baseline characteristics and the proportions of patients receiving glucose-lowering or lipid-lowering drugs and aspirin were similar in the two groups. At 6 months, the mean urinary albumin-to-creatinine ratio was about 20% lower in the aliskiren group than in the placebo group (P<0.001); the corresponding reduction in mean blood pressure was 2/1 mm Hg (P=0.07, systolic; P=0.08, diastolic). A reduction in albuminuria of 50% was seen in 24.7% of aliskiren recipients, compared with 12.5% of placebo recipients. The response to aliskiren did not differ among subgroups of patients, and no between-groups difference was seen in the overall incidence of adverse events. Reported hyperkalemia incidence was 5.0% in the aliskiren group and 5.7% in the placebo group.

Comment: In this preliminary study, the direct renin inhibitor aliskiren appeared to provide temporary renal protection when combined with losartan in patients with diabetes. Further studies are needed to demonstrate (1) that dual therapy to block the renin-angiotensin-aldosterone system with aliskiren or similar agents is renoprotective over a longer period of time; and (2) that such renoprotection translates into true reductions in kidney failure or cardiovascular events.

— Joel M. Gore, MD

Published in Journal Watch Cardiology June 4, 2008

Citation(s):

Parving H-H et al. Aliskiren combined with losartan in type 2 diabetes and nephropathy. N Engl J Med 2008 Jun 5; 358:2433.

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• Medline abstract (Free)

Ingelfinger JR. Aliskiren and dual therapy in type 2 diabetes mellitus. N Engl J Med 2008 Jun 5; 358:2503.

• Original article (Subscription may be required)
• Medline abstract (Free)