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

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.