Dual blockade of the renin-angiotensin-aldosterone system with high-dose angiotensin-converting enzyme inhibitor for nephroprotection: an open, controlled, randomized study.
OBJECTIVE
Despite the proven effectiveness of combination therapy with an angiotensin I-converting enzyme inhibitor (ACEI) and angiotensin II-receptor blockers (ARBs) for the prevention and treatment of kidney disease, it has not proved possible to inhibit the progress of chronic nephropathies completely. To improve renal outcome one may consider using increased dosages of ACEI above those usually recommended for hypertension.


METHODS
A randomized, open, controlled study was conducted to evaluate the influence of two combination therapies on proteinuria, markers of tubular injury and renal fibrosis. A total of 18 patients with a creatinine level of 109+/-36 micromol/l and proteinuria of 0.97+/-0.76 g/24 h were enrolled in the study. In the 8-week run-in period, an ACEI (cilazapril 5 mg once-daily) and an ARB (telmisartan 80 mg once-daily) were administered to achieve the target blood pressure of < or = 130/80 mmHg. Next, the patients were randomly assigned to either an increased dose of cilazapril (10 mg) or the previous dose (5 mg) in two active-treatment periods, each lasting 8 weeks.


RESULTS
A significant increase in renin activity was observed after administration of cilazapril 10 mg (6.46+/-1.12 vs 4.67+/-0.7 ng/ml/h; p=0.028). Proteinuria, urine excretion of N-acetyl-beta-D-glucosaminidase, and alpha1-microglobulin and amino-terminal propeptide of type III procollagen were unchanged.


CONCLUSIONS
An increased dosage of cilazapril (twice the maximum recommended dose) in addition to combination therapy with telmisartan was associated with increased blockade of the renin-angiotensin-aldosterone system, with no additional effect on proteinuria, markers of tubular injury or renal fibrosis.
Tylicki
Leszek
L
Department of Nephrology, Transplantology and Internal Medicine, Medical University of Gdańsk, Gdańsk, Poland. leszek.tylicki@amg.gda.pl
Renke
Marcin
M
Rutkowski
Przemysław
P
Larczyński
Wojciech
W
Aleksandrowicz
Ewa
E
Lysiak-Szydlowska
Wiesława
W
Rutkowski
Bolesław
B
D000118:Acetylglucosaminidase / Q000652:urine; D000293:Adolescent; D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D001562:Benzimidazoles / Q000009:adverse effects / Q000494:pharmacology; D001565:Benzoates / Q000009:adverse effects / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D017315:Cilazapril / Q000009:adverse effects / Q000494:pharmacology*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005355:Fibrosis; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D007674:Kidney Diseases / Q000188:drug therapy / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000652:urine; D011347:Procollagen / Q000652:urine; D011507:Proteinuria / Q000378:metabolism / Q000517:prevention & control*; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology; D000077333:Telmisartan; D055815:Young Adult
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001565:Benzoates; D010446:Peptide Fragments; D011347:Procollagen; C041876:procollagen Type III-N-terminal peptide; D017315:Cilazapril; D000118:Acetylglucosaminidase; D012083:Renin; D000077333:Telmisartan