Effects of dual blockade of the renin angiotensin system in hypertensive type 2 diabetic patients with nephropathy.
OBJECTIVE
To evaluate the effects of combined treatment of an ACE inhibitor and an angiotensin II receptor antagonist on parameters related to the progression of renal disease in type 2 diabetic patients.


METHODS
20 hypertensive type 2 diabetic patients with non-nephrotic proteinuria (0.5 - 3.0 g/day) and estimated creatinine clearance > or = 40 ml/min/1.73m2 were randomly assigned to be treated with perindopril 8 mg/day (Per), irbesartan 300 mg/day (Irb) or a combination of both with the same doses (Per + Irb). Each treatment phase lasting 16 weeks was preceded by a four-week washout period. Diuretics, clonidine and hydralazine were used as supplementary drugs for blood pressure control. Patients were evaluated at baseline and at the end of each treatment phase.


RESULTS
15 (3M/12F) patients completed all the phases. Use of Per, Irb and Per + Irb led to a reduction in 24-hour mean blood pressure of 6 mmHg, 4 mmHg and 4 mmHg, respectively. Changes in glomerular filtration rate were not significant at any phase. Renal plasma flow was significantly more elevated with Irb than Per. Treatment with both Irb and Per + Irb induced similar plasma renin elevation, but treatment with Per did not, suggesting escape. Plasma aldosterone was reduced only by treatment with Per + Irb (-36%, p < 0.02). Reduction in proteinuria during Per + Irb (-33%) was not significantly different from Per (-34%) or Irb (-22%). Urinary transforming growth factor beta1 (TGF-beta1) excretion was significantly reduced with both Irb (-24%, p < 0.05) and Per + Irb (-36%, p < 0.05) but not with Per (-11%, p = 0.60).


CONCLUSIONS
Only combined therapy with irbesartan plus perindopril concurrently reduces plasma aldosterone, proteinuria and urinary TGF-beta1.
Matos
J P S
JP
Hypertension Clinic, Laboratory of Clinical and Experimental Pathophysiology, Rio de Janeiro State University, Rio de Janeiro, Brazil.
de Lourdes Rodrigues
M
M
Ismerim
V L
VL
Boasquevisque
E M
EM
Genelhu
V
V
Francischetti
E A
EA
D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood / Q000187:drug effects; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001713:Biphenyl Compounds / Q000627:therapeutic use; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D003928:Diabetic Nephropathies / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D000077405:Irbesartan; D008297:Male; D008875:Middle Aged; D020913:Perindopril / Q000627:therapeutic use; D012083:Renin / Q000097:blood / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013777:Tetrazoles / Q000627:therapeutic use; D016896:Treatment Outcome
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D001713:Biphenyl Compounds; D013777:Tetrazoles; D000804:Angiotensin II; D000450:Aldosterone; D012083:Renin; D000077405:Irbesartan; D020913:Perindopril