Original Report: Patient-Oriented, Translational Research

Safety and Tolerability of High-Dose Angiotensin Receptor Blocker Therapy in Patients with Chronic Kidney Disease: A Pilot Study
Adam J. Weinberg^a, Dion H. Zappe^b, Michael Ashton^c, Marc S. Weinberg<sup>d

a</sup>College of Arts and Sciences, Boston University, Boston, Mass.,
^bHypertension & Nephrology, Inc., Providence,R.I.,
^cUniversity of Göteborg, Göteborg, Sweden, and
^dDivision of Nephrology, Roger Williams Medical Center, Boston University School of Medicine, Boston,Mass., USA

Address of Corresponding Author

Am J Nephrol 2004;24:340-345 (DOI: 10.1159/000078950)

  Key Words

• Angiotensin-receptor blockers
• Candesartan
• Chronic renal disease
• Diabetic renal disease
• Non-diabetic renal disease
• Renoprotection
• Supramaximal doses

  Abstract

Background: The progression of renal disease is ameliorated by drugs that inhibit the renin-angiotensin system (RAS). The doses used to slow the progression of renal disease may not completely suppress the RAS for 24 h and may explain why some patients do not obtain optimal renoprotective benefits from therapy. This pilot study was initiated to determine the safety and tolerability of using higher doses, than currently approved by the Food and Drug Administration, for the angiotensin-receptor blocker (ARB) candesartan cilexetil in patients with chronic kidney disease. We hypothesized that higher doses will be safe and well tolerated. Consequently, this should be a viable strategy for larger clinical trials evaluating the preservation of renal function. Methods: Twelve patients (10 males; age = 57 ± 14 years) with a history of diabetic or non-diabetic chronic kidney disease were enrolled in an 8-week open-label trial. Patients received candesartan titrated to a targeted dosage of 160 mg/day (5 times above the currently approved maximum dose) and remained at that dosage for the subsequent 4 weeks. The safety and tolerability of the higher doses were determined by measures of blood pressure, serum creatinine and potassium. Results: Candesartan was well tolerated with no serious drug-related adverse events reported. Serum creatinine concentrations throughout the study were not different (p > 0.05) from baseline levels (2.0 ± 0.5 mg/dl). Plasma potassium concentrations at 160 mg/day candesartan (4.9 ± 0.7 mEq/l) were similar (p > 0.05) to those at baseline (4.8 ± 0.5 mEq/l). Conclusions: The results of this pilot study suggest that supramaximal doses of ARBs are safe and well tolerated in patients with chronic kidney disease, while reducing both blood pressure and proteinuria. This study demonstrates the need to further investigate the optimal dosing strategy for ARBs in reducing the progression of renal disease.

Copyright © 2004 S. Karger AG, Basel

  Author Contacts

Marc S. Weinberg, MD
Hypertension & Nephrology, Inc.
1076 North Main Street
Providence, RI 02904 (USA)
Tel. +1 401 8617711, Fax +1 401 4215710, E-Mail Kininmd@aol.com

  Article Information

Received: March 8, 2004
Accepted: April 5, 2004
Published online: June 10, 2004
Number of Print Pages : 6
Number of Figures : 3, Number of Tables : 2, Number of References : 24