The renin-angiotensin system (RAS) is the most important mechanism leading to cardiovascular and renal damage in diabetic patients. Studies conducted until now have unequivocally demonstrated that
antihypertensive treatment with RAS blockers (
angiotensin-converting enzyme (
ACE) inhibitors or
angiotensin-receptor blockers) improve the prognosis of patients with diabetes, by reducing rates of cardiovascular events and preventing or delaying the progression of
diabetic nephropathy. However, despite the benefits of such treatment, cardio-renal events are still very frequent in diabetics. Several strategies for reducing this cardiovascular and renal risk have been proposed, but among them, a more complete blockade of the RAS seems the most attractive.
Direct renin inhibitors are RAS blockers with some particularities, such as their ability to reduce plasma
renin activity or the possibility to modulate tissue and intracellular RAS, which could represent a theoretical advantage when treating diabetic patients. In experimental and clinical studies conducted until now,
aliskiren is able to reduce blood pressure in diabetics, alone or in combination with
ACE inhibitors or
angiotensin-receptor blockers. Moreover,
aliskiren reduces markers of cardiac and renal disease, such as
left ventricular hypertrophy or post-
infarction ventricular remodeling, as well as
proteinuria in diabetics already treated with other RAS blockers. The translation of these promising results to the clinical arena is currently being investigated in the
Aliskiren Trial in
Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE), where more than 8600 diabetic patients with
chronic kidney disease and at high-risk of cardio-renal events are treated with
aliskiren or placebo added to the current treatment consisting of another RAS blocker. If positive,
aliskiren will be the treatment of choice in the prevention of cardiorenal disease in diabetics.