Effect of losartan on uric acid metabolism in children with proteinuric kidney disease: crossover randomized controlled clinical trial.

Abstract

Background: Low uric acid (UA) levels are desirable in kidney disease. Enalapril is the most used reno-protective drug; losartan has a similar antihypertensive and antiproteinuric effect, but also induces hyperuricosuria due to tubular urate transporter 1 inhibition. As this effect has not been demonstrated in paediatrics, we assessed if losartan reduces serum UA in children, owing to an increase in its urinary excretion, compared to enalapril.

Methods: Single-centre, open-label, crossover randomized trial. Patients aged 3-12 years with proteinuric kidney disease and estimated glomerular filtration rate ≥ 30 ml/min/1.73 m², were assigned to receive enalapril or losartan for 30 days. Then, all patients received 15-days of enalapril to washout the effect of losartan in those who received it. Subsequently, they were switched to the opposite treatment modality.

Results: Forty patients were included (36 CKD stage 1, 4 stage 2), median age 8.58 years; median serum UA 4 mg/dL (IQR, 3.5-5.1). Losartan significantly increased median UA urinary fractional excretion from 7% (IQR 6-8.27) to 8.9% (IQR 6.3-11) (p < 0.001) and significantly reduced its median serum level from 4.2 mg/dL (IQR 3.4-4.9) to 3.6 mg/dL (IQR 2.9-4.5) (p < 0.001). Median urinary excretion [pre 6.65% (IQR 5-8.41) vs. post 7% (IQR 5.5-8.3), p = 0.61)] and median serum values [pre 4.2 mg/dL (IQR 3.6-5.1) vs. post 4.1 mg/dL (IQR 3.4-5), p = 0.42)] were comparable with enalapril. The decrease in serum UA levels post-losartan correlated with the increase in its urinary excretion (r = -0.33; p = 0.036).

Conclusions: Losartan significantly increased UA urinary excretion along with the consequent reduction in its serum levels.