title: Supramaximal dose of candesartan in proteinuric renal disease.
abstract: 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 (> or =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 micromol/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.
authors.affiliation: Department of Medicine, University of Calgary, Calgary, Alberta. ellen.burgess@calgaryhealthregion.ca
authors.forename: Ellen
authors.initials: E
authors.lastname: Burgess
authors.forename: Norman
authors.initials: N
authors.lastname: Muirhead
authors.forename: Paul
authors.initials: P
authors.lastname: Rene de Cotret
authors.forename: Anthony
authors.initials: A
authors.lastname: Chiu
authors.forename: Vincent
authors.initials: V
authors.lastname: Pichette
authors.forename: Sheldon
authors.initials: S
authors.lastname: Tobe
mesh_terms: D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy / Q000209:etiology; D007674:Kidney Diseases / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control* / Q000652:urine; D007677:Kidney Function Tests; D007678:Kidney Glomerulus / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000188:drug therapy* / Q000517:prevention & control; D011674:Pulse; D013777:Tetrazoles / Q000627:therapeutic use*
chemical_list: D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; C081643:candesartan