Additive antiproteinuric effect of combined ACE inhibition and angiotensin II receptor blockade.
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.
Ferrari
Paolo
P
Division of Nephrology and Hypertension, Inselspital, University of Berne, Freiburgstrasse 10, 3010 Berne, Switzerland. paolo.ferrari@insel.ch
Marti
Hans-Peter
HP
Pfister
Marc
M
Frey
Felix J
FJ
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
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