AVOID study shows Aliskiren decreasing albuminuria
Jun 12, 2008 - 11:35:08 AM

The much awaited results of the AVOID (Aliskiren in the eValuation of prOteinuria In Diabetes) study were published in the June 5th edition of the New England Journal of Medicine. It is the first study which looked at the kidney-protective benefits of Aliskiren, independent of its proven blood pressure reductions.

About the study
The AVOID study is one of the trials in the landmark ASPIRE HIGHER clinical trial program, the largest ongoing cardio-renal outcomes program involving more than 35,000 patients in 14 trials. The ASPIRE HIGHER program is studying the effect of direct renin inhibition in a variety of cardiac and renal conditions.

Mechanism of action
Aliskiren is an oral renin inhibitor. Renin is secreted by the kidney in response to decreases in blood volume and low renal perfusion. Renin cleaves the peptide angiotensinogen to the inactive decapeptide angiotensin I. Angiotensin I is converted to the active octapeptide angiotensin II by angiotensin-converting enzyme (ACE) produced in the lungs. Angiotensin II is a vasoconstrictor and also promotes aldosterone secretion and sodium reabsorption, which increases blood pressure. It provides a negative feedback to decrease the production of renin. This cycle is known as the renin-angiotensin-aldosterone system. Thus, as a direct renin inhibitor, aliskiren disrupts the RAAS process by decreasing plasma renin activity (PRA).

Method and findings
599 patients were involved in this multinational, randomized, double-blind study. Initially all patients received 100 mg of losartan daily and then they were randomly assigned to receive 6 months of treatment with aliskiren (initially 150 mg and then increased to 300 mg) or placebo, in addition to losartan. The primary outcome seen was a reduction in albuminuria by an additional 20% in type 2 diabetic patients with kidney disease who also had a diagnosis of high blood pressure. These patients were already taking the maximum dose of the angiotensin-receptor blocker (ARB) losartan.As far as side effects were concerned, hyperkalemia reported as an adverse event was seen in 5% of patients taking Aliskiren in addition to losartan, compared to 5.7% of those taking placebo plus losartan. Hyperkalemia as a laboratory abnormality was seen in 13.7% of patients on aliskiren and losartan, compared to 10.8% of the patients taking placebo and losartan.

It, therefore, appears that aliskiren in addition to optimising blood pressure treatment, has additional benefits. But whether a decrease in albuminuria will translate into slowing the decline of renal function is still to be seen . Perhaps, the ALTITUDE study, which is planning to enroll 8500 patients in 36 countries and is due to report results in 2011, will provide the answer.

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