title: Losartan and enalapril are comparable in reducing proteinuria in children with Alport syndrome.
abstract: BACKGROUND
  A previous subgroup analysis of a 12-week, double-blind study demonstrated that losartan significantly lowered proteinuria versus placebo and amlodipine and was well tolerated in children (1-17 years old) with proteinuria secondary to Alport syndrome. The present subgroup analysis of the open-label, extension phase of this study assessed the long-term efficacy and tolerability of losartan versus enalapril.
  
  
  METHODS
  Patients who had completed the double-blind study were re-randomized to losartan or enalapril and followed for proteinuria and renal function for up to 3 years.
  
  
  RESULTS
  Twenty-seven patients with Alport syndrome were randomized to losartan (0.44-2.23 mg/kg/day; n = 15) or enalapril (0.07-0.72 mg/kg/day; n = 12). The least-squares (LS) mean percent change from week 12 in urinary protein to creatinine ratio (UPr/Cr was +1.1 % in the losartan group versus a further 13.9 % reduction in the enalapril group (GMR [95 % CI] = 1.2 [0.7, 2.0]); the LS mean change from week 12 in estimated glomerular filtration rate (eGFR) was -6.4 ml/min/1.73 m(2) in the losartan group versus -9.1 ml/min/1.73 m(2) in the enalapril group. The adverse event incidence was low and comparable in both treatment groups.
  
  
  CONCLUSIONS
  In children with proteinuria secondary to Alport syndrome, losartan maintained proteinuria reduction, and enalapril produced a further proteinuria reduction over the 3-year study period. Both agents were generally well tolerated.
authors.affiliation: Department of Paediatric Nephrology and Wellcome Trust Children's Clinical Research Facility, Manchester Academic Health Science Centre, Royal Manchester Children's Hospital, The University of Manchester, Manchester, UK. nicholas.webb@cmft.nhs.uk
authors.forename: Nicholas J A
authors.initials: NJ
authors.lastname: Webb
authors.forename: Shahnaz
authors.initials: S
authors.lastname: Shahinfar
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Wells
authors.forename: Rachid
authors.initials: R
authors.lastname: Massaad
authors.forename: Gilbert W
authors.initials: GW
authors.lastname: Gleim
authors.forename: Christine
authors.initials: C
authors.lastname: McCrary Sisk
authors.forename: Chun
authors.initials: C
authors.lastname: Lam
mesh_terms: D000293:Adolescent; D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D001208:Asia; D015415:Biomarkers / Q000652:urine; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000652:urine; D004311:Double-Blind Method; D004656:Enalapril / Q000009:adverse effects / Q000627:therapeutic use*; D005060:Europe; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007223:Infant; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D016018:Least-Squares Analysis; D019808:Losartan / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D009394:Nephritis, Hereditary / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology / Q000652:urine; D011507:Proteinuria / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology / Q000652:urine; D013020:South America; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D004656:Enalapril; D003404:Creatinine; D019808:Losartan