Additional Antiproteinuric Effect of Ultrahigh Dose... : Journal of the American Society of Nephrology (original) (raw)

Clinical Nephrology

A Double-Blind, Randomized, Prospective Study

Schmieder, Roland E.; Klingbeil, Arnfried U.; Fleischmann, Erwin H.; Veelken, Roland; Delles, Christian

Department of Medicine IV, University of Erlangen-Nu[Combining Diaeresis]rnberg, Erlangen, Germany

Address correspondence to: Prof. Roland E. Schmieder, Universita[Combining Diaeresis]tsklinikum Erlangen, Medizinische Klinik IV, Krankenhausstrasse 12, Erlangen 91054, Germany. Phone: +49-9131-853-6245; Fax: +49-9131-853-9209; E-mail: [email protected]

Accepted July 14, 2005

Received February 4, 2005

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Abstract

Proteinuria indicates future renal and cardiovascular morbidity, and, conversely, its reduction is associated with improved outcome. In a randomized, double-blind trial with parallel group design, the antiproteinuric effect of candesartan at high doses was analyzed. Patients with normal or mildly impaired renal function, protein excretion rate of 1 to 10 g/d, and treatment with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker for 3 mo were eligible. After a 4-wk treatment with 16 mg/d candesartan, patients (n = 32) were allocated to double-blind therapy with either 32 or 64 mg/d candesartan for 12 wk (including 4 wk of uptitration), followed again by 4 wk of candesartan 16 mg/d. Proteinuria at study entry was similar in both groups (geometric mean [95% confidence interval (CI)]; 32 mg/d candesartan 2.14 g/d [95% CI, 1.45 to 3.17]; 64 mg/d candesartan 2.54 g/d [95% CI, 1.91 to 3.40]; NS). After the double-blind treatment phase, proteinuria was reduced to 1.42 g/d (0.85 to 2.37) in the 64-mg/d group (P = 0.017), without any change in the 32-mg/d group (2.02 g/d [95% CI, 1.26 to 3.26]). The change in proteinuria differed between the two groups in absolute (P = 0.025) and relative terms (−29 ± 50 versus −0 ± 26%; P = 0.012). After downtitration to 16 mg/d candesartan, proteinuria increased again to 2.38 g/d (1.57 to 3.62) in the 64-mg/d group (P = 0.001) but remained unchanged in the 32-mg/d group (2.04 g/d [95% CI, 1.17 to 3.57]; NS). No change in BP was noticed in response to the different doses of candesartan. These data indicate an additive antiproteinuric effect of ultrahigh dose of the angiotensin receptor blocker candesartan compared with standard dose.

Copyright © 2005 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.