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Supramaximal Dose of Candesartan in Proteinuric Renal Disease

Ellen Burgess^*, Norman Muirhead, Paul Rene de Cotret, Anthony Chiu, Vincent Pichette^||, Sheldon Tobe^¶ the SMART (Supra Maximal Atacand Renal Trial) Investigators

^* Department of Medicine, University of Calgary, Calgary, Alberta, Department of Medicine, University of Western Ontario, London, Ontario, Department of Medicine, Université Laval, Québec, Québec, Department of Medicine, University of British Columbia, Vancouver, British Columbia, ^|| Maisonneuve-Rosemont Hôpital, University of Montreal, Montreal, Québec, and ^¶ Department of Medicine, University of Toronto, Toronto, Ontario, Canada

Correspondence: Dr. Ellen Burgess, 1403-29 Street NW, Calgary, AB, Canada T2N2T9. Phone: 403-944-1598; Fax: 403-283-2494; E-mail: ellen.burgess{at}calgaryhealthregion.ca

Received for publication April 23, 2008. Accepted for publication October 28, 2008.

High levels of proteinuria predict renal deterioration, suggesting that interventions to reduce proteinuria may postpone the development of severe renal impairment. This multicenter Canadian trial evaluated whether supramaximal dosages of candesartan would reduce proteinuria to a greater extent than the maximum approved antihypertensive dosage. The authors randomly assigned 269 patients who had persistent proteinuria (1 g/d) despite 7 wk of treatment with the highest approved dosage of candesartan (16 mg/d) to 16, 64, or 128 mg/d candesartan for 30 wk. The median serum creatinine level was 130.0 µmol/L (1.47 mg/dl), and the median urinary protein excretion was 2.66 g/d; most (53.9%) patients had diabetic nephropathy. The mean difference of the percentage change in proteinuria for patients receiving 128 mg/d candesartan compared with those receiving 16 mg/d candesartan was –33.05% (95% confidence interval –45.70 to –17.44; P < 0.0001). Reductions in BP were not different across the three treatment groups. Elevated serum potassium levels (K⁺ > 5.5 mEq/L) led to the early withdrawal of 11 patients, but there were no dosage-related increases in adverse events. In conclusion, proteinuria that persists despite treatment with the maximum recommended dosage of candesartan can be reduced by increasing the dosage of candesartan further, but serum potassium levels should be monitored during treatment.

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Copyright © 2009 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673