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

Abstract

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 18.1 mg/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.

• Authors: Nicholas J A Webb, Chun Lam, Shahnaz Shahinfar, Juergen Strehlau, Thomas G Wells, Gilbert W Gleim, Céline Le Bailly De Tilleghem
• Journal: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association (Nephrol Dial Transplant) Vol. 26 Issue 8 Pg. 2521-6 (Aug 2011) ISSN: 1460-2385 [Electronic] England
• PMID: 21285125 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antihypertensive Agents
• Amlodipine
• Losartan

Topics

• Adolescent
• Adult
• Amlodipine (therapeutic use)
• Antihypertensive Agents (therapeutic use)
• Blood Pressure (drug effects)
• Child
• Child, Preschool
• Double-Blind Method
• Female
• Follow-Up Studies
• Humans
• Hypertension (drug therapy)
• Infant
• Losartan (therapeutic use)
• Male
• Nephritis, Hereditary (drug therapy)
• Prognosis
• Prospective Studies
• Proteinuria (chemically induced, drug therapy)
• Survival Rate
• Treatment Outcome
• Young Adult