Effects of combined ACE inhibitor and angiotensin II antagonist treatment in human chronic nephropathies.
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.
Campbell
Ruth
R
Clinical Research Center for Rare Diseases "Aldo and Cele Daccò," Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
Sangalli
Fabio
F
Perticucci
Elena
E
Aros
Claudio
C
Viscarra
Cecilia
C
Perna
Annalisa
A
Remuzzi
Andrea
A
Bertocchi
Federico
F
Fagiani
Luca
L
Remuzzi
Giuseppe
G
Ruggenenti
Piero
P
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
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001552:Benzazepines; D003911:Dextrans; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine; C044946:benazepril