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Losartan and enalapril are comparable in reducing proteinuria in children
Nicholas J A Webb1, Shahnaz Shahinfar, Thomas G Wells
1Department 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
Insights
Losartan and enalapril effectively reduced proteinuria in children with chronic kidney disease. Both medications were well-tolerated, with losartan showing fewer drug-related adverse events than enalapril over three years.
Area of Science:
- Pediatric Nephrology
- Pharmacology
- Chronic Kidney Disease Research
Background:
- Angiotensin-converting enzyme inhibitors and angiotensin II type I receptor blockers are used in adults with chronic kidney disease (CKD).
- Their efficacy and safety in pediatric populations, with distinct CKD causes, remain uncertain.
- Previous trials established the antiproteinuric effects of these drug classes in children.
Purpose of the Study:
- To evaluate the long-term efficacy and safety of losartan compared to enalapril in children with proteinuria.
- To assess the impact of these agents on proteinuria and estimated glomerular filtration rate (eGFR) over three years.
Main Methods:
- An open-label extension of a prior blinded trial involving 268 children with proteinuria.
- Re-randomization to either losartan or enalapril, with follow-up until 100 patients completed 3 years.
- Monitoring of urinary protein/creatinine ratio and eGFR for efficacy and adverse events like hyperkalemia and renal dysfunction.
Main Results:
- Both losartan and enalapril significantly reduced proteinuria, with greater reduction seen with enalapril (40.45%) versus losartan (30.01%).
- Mean eGFR showed a slight increase with enalapril (7.0 ml/min/1.73 m²) and a smaller increase with losartan (3.3 ml/min/1.73 m²).
- Adverse events, including hyperkalemia and renal dysfunction, were infrequent and similar between groups; losartan had fewer drug-related adverse events.
Conclusions:
- Losartan and enalapril are effective in reducing proteinuria in children with CKD without significant adverse effects on eGFR.
- Both agents demonstrated sustained efficacy and good tolerability over a 3-year period.
- Losartan may offer a favorable safety profile with fewer drug-related adverse events compared to enalapril in this pediatric population.
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.
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