Abstract
The prevention and the treatment with drugs interacting with the renin-angiotensin
system (RAAS) are one of the greatest successes of the pharmacological research in
the last years. Many trials demonstrated the efficacy of ARBs and ACEi in preventing
or reducing the progression of albuminuria, the loss of kidney function and the mortality
in diabetic population.
The rationale for applying a dual RAAS blockade is based on data showing that ACEi
mono-therapy produces an incomplete RAAS blockade with angiotensin I and renin accumulation
and the subsequent angiotensin II ‘escape’ production by non-ACE pathways. The use
of ARBs and ACEi in combination could lead to a stronger RAAS block and consequently
to a more effective nephroprotection. Years ago, some studies performed in small groups
of patients with diabetic nephropathy confirmed the effectiveness of this pharmacological
approach.
In contrast recent important trials, like ONTARGET, ALTITUDE and VA NEPHRON-D failed
to demonstrate the effectiveness of this therapeutic strategy, suggesting that probably
not all the diabetic patients with nephropathy should be considered equal as regard
the response to this therapy. These 3 long-term studies showed that the dual blockade
of RAAS may bring cardiovascular and renal adverse events, even in presence of a reduction
of albuminuria. Dual blockade of RAAS is not currently feasible in patients with diabetic
nephropathy, but we consider that the effort to try to apply a complete RAAS blockade
should be pursued and that probably through an accurate selection of patients in the
future we could reconsider this kind of therapy.
Key words
diabetic nephropathy - hypertension - RAAS blockade - albuminuria
