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Correspondence to Dr. Giuseppe Remuzzi, Mario Negri Institute for Pharmacological Research, Negri Bergamo Laboratories, Via Gavazzeni, 11-24125
Bergamo, Italy. Phone: 39-035-319-888; Fax: 39-035-319-331; E-mail:
gremuzzi@marionegri.it
1046-6673/1512-0064
Journal of the American Society of Nephrology
Copyright 2004 by the American Society of Nephrology
DOI: 10.1097/01.ASN.0000093368.27046.3C
S65
Type 2 Diabetes. Two rigorously powered trials that included 1500 patients, the Irbesartan in Diabetic Nephropathy
Trial (IDNT) (23) and the Reduction of Endpoints in Type 2
Diabetes Mellitus with the Angiotensin II Antagonist Losartan
(RENAAL) trial (24), compared ARB with conventional therapy in patients with type 2 diabetes and overt nephropathy. In
these two studies, ARB treatment reduced the relative risk of
reaching the primary composite end point (doubling of serum
creatinine, ESRD, or death) by 20% and 16%, respectively. In
addition, the IDNT showed a reduction of the risk to reach the
primary end point by 23% also as compared with calcium
channel blockade by amlodipine, the third treatment arm in this
study.
Recently, the Microalbuminuria Reduction with Valsartan
study (25) and the Irbesartan in Patients with Type 2 Diabetes
and Microalbuminuria study (26) showed the beneficial effect
of ARB also at the stage of incipient nephropathy. In the
Microalbuminuria Reduction with Valsartan study, valsartan
reduced albuminuria by 44%, compared with an 8% reduction
in the control arm with amlodipine. Moreover, normoalbuminuria was restored in 30% of the patients who were treated with
valsartan (versus 15% with amlodipine). The Irbesartan in
Patients with Type 2 Diabetes and Microalbuminuria study
showed, in addition to a clear-cut reduction of the primary end
point overt nephropathy (i.e., progression to macroalbuminuria), a 24% and 38% decrease in albuminuria with irbesartan
150 mg and 300 mg, respectively, whereas albuminuria remained almost unchanged (2%) in the placebo arm.
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Figure 1. Risk reduction of ESRD achieved by angiotensin-converting enzyme inhibition or angiotensin receptor blockade versus placebo plus
conventional treatment in large, prospective trials in patients with and without diabetes and overt nephropathy.
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bined treatment with the ARB candesartan and the ACE inhibitor lisinopril resulted in stronger BP reduction than monotherapy (27).
In summary, these data show the added renoprotective benefit of combined RAS blockade, at least in nondiabetic renal
disease and incipient nephropathy of type 2 diabetes. Nevertheless, the cardiovascular effects of such a regimen remain to
be established.
In the COOPERATE trial, dual RAS blockade with trandolapril and losartan reduced the risk to reach the primary
composite end point of doubling of serum creatinine or ESRD
by almost 50% as compared with the single agents. The advantage was explained by the superior 75% reduction of proteinuria in the combined group compared with 40 to 45%
reduction with monotherapy (9).
Conclusions
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Acknowledgments
G.D.L. is awarded a Marie-Curie fellowship of the European
Union. G.J. Navis provided valuable comments on the manuscript.
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