Renoprotective Effects of Adding Angiotensin II Receptor Blocker to Maximal Recommended Doses of ACE Inhibitor in Diabetic Nephropathy
A randomized double-blind crossover trial
A randomized double-blind crossover trial
Abstract
OBJECTIVE—We evaluated the renoprotective effects as reflected by short-term changes in albuminuria of dual blockade of the renin-angiotensin system (RAS) by adding an angiotensin II receptor blocker (ARB) to treatment with maximal recommended doses of an ACE inhibitor (ACEI) in patients with type 2 diabetes and nephropathy.
RESEARCH DESIGN AND METHODS—A total of 20 patients (17 men and 3 women) with type 2 diabetes along with hypertension and nephropathy were enrolled in this double-blind, randomized, two-period, crossover trial of 8 weeks of treatment with the ARB candesartan 16 mg daily and placebo added in random order to existing treatment with lisinopril/enalapril 40 mg daily or captopril 150 mg daily. At the end of each treatment period, we evaluated albuminuria in three 24-h urinary collections by turbidimetry, 24-h ambulatory blood pressure (ABP) using the Takeda-TM2420, and glomerular filtration rate (GFR) by the 51Cr-EDTA plasma-clearance technique.
RESULTS—During monoblockade of the RAS by ACEI treatment, albuminuria was 706 (349−1,219) mg/24 h [geometric mean (IQR)]; 24-h ABP was 138 ± 3/72 ± 2 mmHg (mean ± SE); and GFR was 77 ± 6 ml · min−1 · 1.73 m−2 (mean ± SE). During dual blockade of the RAS by addition of candesartan 16 mg daily, there was a mean (95% CI) reduction in albuminuria of 28 (17−38) compared with ACEI alone (P < 0.001). There was a modest reduction in systolic/diastolic 24-h ABP of 3/2 mmHg (−2 to 8 systolic, −2 to 5 diastolic; NS). Changes in albuminuria did not correlate to changes in ABP. Addition of candesartan 16 mg daily induced a small, insignificant decrease in GFR of 4 (−1 to 9) ml · min−1 · 1.73 m−2.
CONCLUSIONS—Dual blockade of the RAS provides superior short-term renoprotection independent of systemic blood pressure changes in comparison with maximally recommended doses of ACEI in patients with type 2 diabetes as well as nephropathy.
- ABP, ambulatory blood pressure
- ACEI, ACE inhibitor
- ARB, angiotensin II receptor blocker
- GFR, glomerular filtration rate
- RAS, renin-angiotensin system
- TGF-β, transforming growth factor-β
Footnotes
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A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
H.H.P. has served as a consultant to Merck, Bristol-Myers Squibb, Sanofi, Pfizer, and BioStratum; has received research grants from Merck, Bristol-Myers Squibb, Sanofi, and AstraZeneca; and has been a member of the speakers bureaus sponsored by Merck, Bristol-Myers Squibb, Sanofi, Pfizer, and AstraZeneca.
- Accepted April 25, 2003.
- Received January 27, 2003.
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