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Clinical Care/Education/Nutrition

Renoprotective Effects of Adding Angiotensin II Receptor Blocker to Maximal Recommended Doses of ACE Inhibitor in Diabetic Nephropathy

A randomized double-blind crossover trial

  1. Kasper Rossing, MD1,
  2. Peter Jacobsen, MD1,
  3. Lotte Pietraszek1 and
  4. Hans-Henrik Parving, DMSC, MD, PROF12
  1. 1Steno Diabetes Center, Gentofte, Denmark
  2. 2Faculty of Health Science, University of Aarhus, Aarhus, Denmark
  1. Address correspondence and reprint requests to Kasper Rossing, MD, Steno Diabetes Center, Niels Steensens Vej 2, 2820 Gentofte, Denmark. E-mail: krossing{at}dadlnet.dk
Diabetes Care 2003 Aug; 26(8): 2268-2274. https://doi.org/10.2337/diacare.26.8.2268
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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

  • 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.
  • DIABETES CARE
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Diabetes Care: 26 (8)

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August 2003, 26(8)
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Renoprotective Effects of Adding Angiotensin II Receptor Blocker to Maximal Recommended Doses of ACE Inhibitor in Diabetic Nephropathy
Kasper Rossing, Peter Jacobsen, Lotte Pietraszek, Hans-Henrik Parving
Diabetes Care Aug 2003, 26 (8) 2268-2274; DOI: 10.2337/diacare.26.8.2268

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Renoprotective Effects of Adding Angiotensin II Receptor Blocker to Maximal Recommended Doses of ACE Inhibitor in Diabetic Nephropathy
Kasper Rossing, Peter Jacobsen, Lotte Pietraszek, Hans-Henrik Parving
Diabetes Care Aug 2003, 26 (8) 2268-2274; DOI: 10.2337/diacare.26.8.2268
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