Impact of glycaemic control on the effect of direct renin inhibition in the AVOID study

INTRODUCTION: Hyperglycaemia induces development and progression of microvascular complications in diabetes. A direct link between high glucose levels and intrarenal renin-angiotensin activation has been demonstrated. This post-hoc analysis assessed the influence of baseline glycaemic control on the reduction of albuminuria with aliskiren or placebo added to losartan in the Aliskiren in the EValuation of PrOteinuria In Diabetes (AVOID) study. MATERIALS AND METHODS: In AVOID, 599 patients with type 2 diabetes, hypertension and nephropathy received 6 months' aliskiren or placebo added to losartan 100 mg and optimal antihypertensive therapy. Changes in urinary albumin creatinine ratio at end of study were assessed by tertiles of baseline HbA(1c) levels. RESULTS: Patients were divided into tertiles of HbA(1c) (<7.1%, 7.1 to <8.4% and ≥8.4%). There were no differences between tertiles, except patients in the highest tertile group more frequently used insulin. The antiproteinuric effect of aliskiren was consistent across tertiles, with the largest effect in the highest tertile (HbA(1c) ≥8.4%). CONCLUSIONS: This post-hoc analysis of the AVOID study suggests that renin inhibition with aliskiren 300 mg once daily added to losartan 100 mg once daily plus optimal antihypertensive therapy provides reductions in urinary albumin creatinine ratio that are efficacious in all, but particularly in poorly controlled, diabetic patients.