June 4, 2008Beyond Blood Pressure Control: Targeting

Proteinuria with Renin-Angiotensin-Aldosterone

Inhibitors
Joel M. Gore, MD reviewing Parving H-H et al. N Engl J Med 2008 Jun 5. Ingelfinger
JR. N Engl J Med 2008 Jun 5. 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.
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.
PubMed abstract (Free)
1. Ingelfinger JR. Aliskiren and dual therapy in type 2 diabetes mellitus. N Engl J Med 2008 Jun 5; 358:2503. - See
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