ACEI and ARB combination therapy in patients with macroalbuminuric diabetic nephropathy and low socioeconomic level: a double-blind randomized clinical trial

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Citações na Scopus
35
Tipo de produção
article
Data de publicação
2011
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ISSN da Revista
Título do Volume
Editora
DUSTRI-VERLAG DR KARL FEISTLE
Citação
CLINICAL NEPHROLOGY, v.76, n.4, p.273-283, 2011
Projetos de Pesquisa
Unidades Organizacionais
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Resumo
Objective: The combination of an ACE inhibitor (ACEI) and an angiotensin II receptor blocker (ARB) has been proposed for the treatment of diabetic nephropathy (DN), but doubts remain about its efficacy and safety. We compared the effects of combination therapy and ACEI monotherapy on proteinuria and on three urinary inflammatory cytokines (MCP-1, TGF-beta and VEGF). Design and patients: 56 patients with macro-albuminuric DN received 40 mg/d enalapril for 4 months, followed by add-on 100 mg/d losartan or placebo for another 4 months. The primary and secondary endpoints were reduction of proteinuria and cytokine levels, respectively. Results: Proteinuria did not fall in either group. Repeated measures ANOVA revealed no difference between groups. A high side effect rate was observed (28.5%). Finally, unadjusted logistic regression showed no difference between groups, but after adjustments the risk of worsening proteinuria was higher in the combination therapy group (p = 0.04). The same pattern was observed for urinary MCP-1. Conclusion: These results suggest that 1) in advanced DN with severe proteinuria and poor metabolic control, angiotensin II blockade may be less effective than in other groups of CKD patients. 2) In such patients, combination therapy may not afford superior renoprotection compared to enalapril. 3) Urinary MCP-1 is a promising biomarker for the response to ACEI and/or ARB treatment and for the risk of associated unwanted effects.
Palavras-chave
diabetic nephropathy, proteinuria, ACE inhibitor, angiotensin II receptor blocker, chronic kidney disease, MCP-1, VEGF, TGF-beta
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