title: Effects of combined ACE inhibitor and angiotensin II antagonist treatment in human chronic nephropathies.
abstract: BACKGROUND
  Proteinuria predicts renal disease progression, and its reduction by angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor antagonists (ARA) is renoprotective.
  
  
  METHODS
  In this prospective, randomized, cross-over study of 24 patients with nondiabetic, chronic nephropathies, we compared the effects on proteinuria, renal hemodynamics, and glomerular permselectivity of 8 weeks with comparable blood pressure control achieved by benazepril (10 mg/day) and valsartan (80 mg/day) combined therapy with those achieved by benazepril (20 mg/day) or valsartan (160 mg/day) alone.
  
  
  RESULTS
  Despite comparable changes in blood pressure and glomerular filtration rate (GFR), combined therapy decreased proteinuria more than benazepril (-56% vs. -45.9%, P=0.02) and valsartan (-41.5%, P=0.002). Changes in urinary protein to creatinine ratio followed the same trend. Filtration fraction and renal vascular resistances (RVR) decreased more with combined (-14.7%,-23.7%) or benazepril (-12.4%, -20.5%) than with valsartan (-2.7%, -12.5%, P < 0.05 vs. both). RVR changes, adjusted for GFR changes, were associated with those in proteinuria (P < 0.05). Changes in glomerular permeability were comparable and did not predict different changes in proteinuria in the three groups.
  
  
  CONCLUSIONS
  At comparable blood pressure, combined ACEi and ARA decreased proteinuria better than ACEi and ARA. The greater antiproteinuric effect most likely depended on an ACEi-related hemodynamic effect, in addition to glomerular size selectivity amelioration. Long-term combined ACEi and ARA therapy may be more renoprotective than treatment with each agent alone.
authors.affiliation: Clinical Research Center for Rare Diseases "Aldo and Cele Daccò," Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
authors.forename: Ruth
authors.initials: R
authors.lastname: Campbell
authors.forename: Fabio
authors.initials: F
authors.lastname: Sangalli
authors.forename: Elena
authors.initials: E
authors.lastname: Perticucci
authors.forename: Claudio
authors.initials: C
authors.lastname: Aros
authors.forename: Cecilia
authors.initials: C
authors.lastname: Viscarra
authors.forename: Annalisa
authors.initials: A
authors.lastname: Perna
authors.forename: Andrea
authors.initials: A
authors.lastname: Remuzzi
authors.forename: Federico
authors.initials: F
authors.lastname: Bertocchi
authors.forename: Luca
authors.initials: L
authors.lastname: Fagiani
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Remuzzi
authors.forename: Piero
authors.initials: P
authors.lastname: Ruggenenti
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001552:Benzazepines / Q000008:administration & dosage*; D002908:Chronic Disease; D018592:Cross-Over Studies; D003911:Dextrans / Q000493:pharmacokinetics; D004359:Drug Therapy, Combination; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005922:Glomerulonephritis, IGA / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011507:Proteinuria / Q000188:drug therapy*; D012079:Renal Circulation / Q000187:drug effects; D013777:Tetrazoles / Q000008:administration & dosage*; D014633:Valine / Q000008:administration & dosage* / Q000031:analogs & derivatives; D000068756:Valsartan
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001552:Benzazepines; D003911:Dextrans; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine; C044946:benazepril