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

Abstract

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

Design, setting, participants, & measurements: 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.

Results: 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.

Conclusions: 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.

Figure 1.

Study design.

Figure 2.

Disposition of patients.

Figure 3.

Change from baseline in protein/creatinine ratio (g/g) at week 12 in (A) hypertensive and normotensive children (n = 302), (B) hypertensive children (n = 59), and (C) normotensive children (n = 243).

Figure 4.

Ratio in geometric mean protein/creatinine ratio (g/g at week 12 by subgroup, point estimate and 95% CI. n = number in losartan group, number in amlodipine/placebo group. TS, Tanner stage; US, United States.

Figure 5.

Relationship between reduction in proteinuria and systolic BP in (A) hypertensive and normotensive children (n = 302), (B) hypertensive children (n = 59), and (C) normotensive children (n = 243).