title: ACEI and ARB combination therapy in patients with macroalbuminuric diabetic nephropathy and low socioeconomic level: a double-blind randomized clinical trial.
abstract: 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).
  
  
  METHODS
  56 patients with macroalbuminuric DN received 40 mg/d enalapril for 4 months, followed by add-on 100 mg/day 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Renal Division, Department of Clinical Medicine, University of São Paulo, Brazil. silviatitan@superig.com.br
authors.forename: S M
authors.initials: SM
authors.lastname: Titan
authors.forename: J
authors.initials: J
authors.lastname: M Vieira
authors.forename: W V
authors.initials: WV
authors.lastname: Dominguez
authors.forename: R T
authors.initials: RT
authors.lastname: Barros
authors.forename: R
authors.initials: R
authors.lastname: Zatz
mesh_terms: D000704:Analysis of Variance; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D015415:Biomarkers / Q000652:urine; D016009:Chi-Square Distribution; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D016015:Logistic Models; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000188:drug therapy*; D012923:Social Class; D016896:Treatment Outcome
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D004656:Enalapril; D019808:Losartan