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Exp Clin Endocrinol Diabetes 2016; 124(06): 361-366
DOI: 10.1055/s-0042-101242
Review
© Georg Thieme Verlag KG Stuttgart · New York

Disputes in the Treatment of Diabetic Nephropathy: The Dual Blockade of Renin-Angiotensin System

E. Grolla
1   Department of Cardiology, “Dell’Angelo” Hospital, Mestre (Venice), Italy
,
L. Bonanni
2   Department of Internal Medicine, “Dell’Angelo” Hospital, Mestre (Venice), Italy
,
A. Cutolo
1   Department of Cardiology, “Dell’Angelo” Hospital, Mestre (Venice), Italy
,
F. Presotto
2   Department of Internal Medicine, “Dell’Angelo” Hospital, Mestre (Venice), Italy
,
M. Dalla Vestra
2   Department of Internal Medicine, “Dell’Angelo” Hospital, Mestre (Venice), Italy
› Author Affiliations
Further Information

Publication History

received 04 November 2015
first decision 30 December 2015

accepted 20 January 2016

Publication Date:
24 May 2016 (online)

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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

Next part of this series:

Hypertension and Diabetic NephropathyExp Clin Endocrinol Diabetes 2016; 124(06): 333-334
DOI: 10.1055/s-0042-110231

 

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