Randomized, double-blind, controlled study of losartan in children with proteinuria

No large, randomized, double-blind trials in children with proteinuria treated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers have previously been reported.

This 12-week, double-blind, multinational study investigated the effects of losartan 0.7 to 1.4 mg/kg per day compared with placebo (normotensive stratum) or amlodipine 0.1 to 0.2 mg/kg per day up to 5 mg/d (hypertensive stratum) on proteinuria (morning-void urinary protein-creatinine ratio, baseline > or =0.3 g/g) in 306 children up to 17 years of age.

Twelve weeks of treatment with losartan significantly reduced proteinuria compared with amlodipine/placebo: losartan -35.8% (95% confidence interval: -27.6% to -43.1%) versus amlodipine/placebo 1.4% (95% confidence interval: -10.3% to 14.5%), P < or = 0.001. Significance remained after adjustment for differences across treatment groups in change in BP (losartan produced incremental systolic and diastolic BP reductions versus amlodipine of 5.4 and 4.6 mmHg, respectively; and versus placebo of 3.8 and 4.0 mmHg, respectively). Proteinuria reduction was consistently observed in the normotensive (-34.4% losartan; 2.6% placebo) and hypertensive (-41.5% losartan; 2.4% amlodipine) strata, and in all prespecified subgroups, including age, gender, race, Tanner stage, weight, prior therapy with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, as well as among the most common etiologies of proteinuria. Adverse event incidence was low and comparable in all groups.

Losartan significantly lowered proteinuria and was well tolerated after 12 weeks in children aged 1 to 17 years with proteinuria with or without hypertension, a population that has not previously been rigorously studied.