Efficacy and safety of losartan in children with Alport syndrome-results from a subgroup analysis of a prospective, randomized, placebo- or amlodipine-controlled trial

Background. No prospective, randomized, double-blind trials of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers have previously been reported in adults or children with proteinuria secondary to Alport syndrome. Methods. This 12-week, double-blind multinational study investigated the effects of losartan 0.7-1.4 mg/kg/day compared with placebo (normotensive patients) or amlodipine 0.1-0.2 mg/kg/day up to 5 mg/day (hypertensive patients) on proteinuria [early morning-void urinary protein/creatinine ratio (UPr/Cr), baseline >= 34 mg/mmol] in 30 children of up to 17 years of age with Alport syndrome. Results. Twelve weeks of treatment with losartan significantly reduced proteinuria compared with placebo/amlodipine: losartan -14.7 mg/mmol (interquartile range -49.7 to -5.7 mg/mmol) or 31.6% reduction using a mixed model approach versus placebo/amlodipine 2.3 mg/mmol (-26.0 to 18.1mg/mmol), P = 0.01 or 2.3% increase using a mixed model approach. Adverse event incidence was low and comparable between losartan and placebo/amlodipine groups. Conclusions. Losartan significantly lowered proteinuria and was well tolerated after 12 weeks of treatment in children aged 1-17 years with proteinuria secondary to Alport syndrome with or without hypertension, a population that has not previously been rigorously studied.