title: Additive antiproteinuric effect of combined ACE inhibition and angiotensin II receptor blockade.
abstract: BACKGROUND
  Limitation of systemic and glomerular hypertension reduces urinary protein excretion and prevents renal function deterioration.
  
  
  OBJECTIVE
  To investigate whether, in hypertensive patients with glomerulonephritis, a combination of an angiotensin converting enzyme inhibitor (ACEI, fosinopril 20 mg/day) with an angiotensin receptor blocker (ARB, irbesartan 150 mg/day) produces a more profound antiproteinuric effect than either drug alone.
  
  
  METHODS
  Ten non-diabetic patients with glomerulonephritis, normal or slightly reduced but stable renal function (creatinine clearance 40-106 ml/min) without immunosuppression were studied. Clinical evaluations, 24 h blood pressure measurements and laboratory tests were performed as follows: (1) without medication (baseline) and in random sequence; (2) ACEI alone; (3) ARB alone; and (4) combination of ACEI + ARB. Each period lasted for 6 weeks, separated by three washout periods of 4 weeks each without therapy.
  
  
  RESULTS
  ACEI and ARB alone reduced proteinuria from 7.9 +/- 7.1 to 5.3 +/- 5.2 and 5.0 +/- 4.9 g/24 h (mean +/- SD), respectively. The combination of ACEI + ARB induced a more remarkable reduction of proteinuria in every patient (to 3.3 +/- 3.7 g/24 h) than either drug alone (P = 0.039 by ANOVA). The enhanced antiproteinuric effect of the combined therapy could not be attributed to a more pronounced reduction of 24 h mean arterial pressure (basal, 106 +/- 8; ACEI, 97 +/- 5; ARB, 98 +/- 5; ACEI+ARB, 95 +/- 5 mmHg) or creatinine clearance (basal, 77 +/- 27; ACEI, 73 +/- 31; ARB 80 +/- 30; ACEI + ARB, 73 +/- 32 ml/min).
  
  
  CONCLUSIONS
  A combination of ACEI and ARB in patients with glomerulonephritis produces a more profound decrease in proteinuria than either drug alone. This additive antiproteinuric effect is not dependent on changes in blood pressure or creatinine clearance. A long-term controlled study is required to confirm the positive effect of this treatment on the progression of renal function loss.
authors.affiliation: Division of Nephrology and Hypertension, Inselspital, University of Berne, Freiburgstrasse 10, 3010 Berne, Switzerland. paolo.ferrari@insel.ch
authors.forename: Paolo
authors.initials: P
authors.lastname: Ferrari
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Marti
authors.forename: Marc
authors.initials: M
authors.lastname: Pfister
authors.forename: Felix J
authors.initials: FJ
authors.lastname: Frey
mesh_terms: D000328:Adult; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D018660:Blood Pressure Monitoring, Ambulatory; D002940:Circadian Rhythm; D003404:Creatinine / Q000097:blood; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D017328:Fosinopril / Q000627:therapeutic use; D006801:Humans; D000077405:Irbesartan; D008297:Male; D008875:Middle Aged; D011188:Potassium / Q000097:blood; D011507:Proteinuria / Q000188:drug therapy*; D011945:Receptors, Angiotensin / Q000627:therapeutic use*; D013777:Tetrazoles / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D001713:Biphenyl Compounds; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D003404:Creatinine; D000077405:Irbesartan; D017328:Fosinopril; D011188:Potassium