title: Losartan and enalapril are comparable in reducing proteinuria in children.
abstract: Angiotensin-converting enzyme inhibitors and angiotensin II type I receptor blockers delay progression of chronic kidney disease and have antiproteinuric effects beyond their effects on blood pressure. They are routinely used in adults; however, their efficacy and safety in children, in whom the causes of chronic kidney disease are significantly different relative to adults, is uncertain. Here we assessed an open-label extension of a previous 3-month blinded trial, in which the efficacy and tolerability of losartan was compared to placebo or amlodipine in 306 normotensive and hypertensive children with proteinuria. In this study, 268 children were re-randomized to losartan or enalapril and followed until 100 patients completed 3 years of follow-up for proteinuria and renal function. The least squares percent mean reduction from baseline in the urinary protein/creatinine ratio was 30.01% for losartan and 40.45% for enalapril. The least squares mean change from baseline in eGFR was 3.3 ml/min per 1.73 m2 for losartan and 7.0 ml/min per 1.73 m2 for enalapril. The incidence of specific adverse events such as hyperkalemia and renal dysfunction was low and similar in both groups. Both were generally well tolerated and, overall, fewer drug-related adverse events occurred with losartan than with enalapril. Thus, in children with proteinuria, losartan and enalapril significantly reduced proteinuria without any appreciable changes in eGFR, effects that were maintained throughout the study. Both losartan and enalapril were generally well tolerated.
authors: Department of Paediatric Nephrology and Wellcome Trust Children's Clinical Research Facility, The University of Manchester, Manchester Academic Health Science Centre, Royal Manchester Children's Hospital, Manchester, UK. nicholas.webb@cmft.nhs.uk
authors: Nicholas J A
authors: NJ
authors: Webb
authors: Shahnaz
authors: S
authors: Shahinfar
authors: Thomas G
authors: TG
authors: Wells
authors: Rachid
authors: R
authors: Massaad
authors: Gilbert W
authors: GW
authors: Gleim
authors: Emanuela P
authors: EP
authors: Santoro
authors: Christine M
authors: CM
authors: Sisk
authors: Chun
authors: C
authors: Lam
mesh_terms: D000293:Adolescent; D000367:Age Factors; D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000652:urine; D055316:Cystatin C / Q000097:blood; D004656:Enalapril / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D016018:Least-Squares Analysis; D019808:Losartan / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D011507:Proteinuria / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology / Q000652:urine; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology / Q000652:urine; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; C525030:CST3 protein, human; D055316:Cystatin C; D004656:Enalapril; D003404:Creatinine; D019808:Losartan