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.

Trial registration: ClinicalTrials.gov NCT00242346.

Figure 1.

Study design for the trial.

Figure 2.

Patient flow chart and outcomes.

Figure 3.

Percentage reduction in 24-h proteinuria at weeks 6 and 30 by candesartan dosage. Number of patients for 64-mg treatment arm were 88 and for the 128-mg treatment arm were 82 and 83 for weeks 6 and 30, respectively. **P < 0.0001

Figure 4.

Correlation between changes in SBP and changes in proteinuria.