Aliskiren in combination with an angiotensin-receptor blocker has a moderate additive effect in reducing proteinuria in patients with diabetic nephropathy.
Aliskiren (Tekturna), a direct renin inhibitor, was FDA-approved in 2007 for treatment of hypertension. Researchers conducted this industry-sponsored randomized trial to determine whether dual blockade of the renin-angiotensin-aldosterone system — with the combination of aliskiren and the angiotensin-receptor blocker losartan — reduces proteinuria in patients with diabetic nephropathy. The trial involved 599 patients with type 2 diabetes, hypertension, and nephropathy (urinary albumin-to-creatinine ratio between 300 and 3500 mg/g). Patients with glomerular filtration rate (GFR) <30 mL/min or serum potassium >5.1 mEq/L were excluded.
Patients received either losartan plus aliskiren or losartan plus placebo. At 6 months, the mean urinary albumin-to-creatinine ratio was significantly reduced by 20% in the aliskiren group, compared with the placebo group. Mean blood pressure was significantly lower with aliskiren than with placebo, but only by 2 mm Hg (systolic) and 1 mm (diastolic). GFR did not differ significantly between the groups.
Comment: This trial demonstrates that aliskiren in combination with an angiotensin-receptor blocker has a moderate additive effect in reducing proteinuria in patients with diabetic nephropathy. However, the study’s duration was too short to examine clinical endpoints (e.g., progression to advanced or end-stage renal disease) or to ensure long-term safety. Thus, use of aliskiren solely to reduce proteinuria seems premature at this time.
— Allan S. Brett, MD
Published in Journal Watch General Medicine June 4, 2008
Parving H-H et al. Aliskiren combined with losartan in type 2 diabetes and nephropathy. N Engl J Med 2008 Jun 5; 358:2433.