What are the implications of hyperuricemia in pediatric patients?

From the Guidelines

Hyperuricemia in pediatric patients should be promptly treated with rasburicase to rapidly reduce uric acid levels and prevent potential complications, as evidenced by studies showing its superiority over allopurinol in this population. The management of hyperuricemia in children is crucial to prevent long-term consequences such as kidney damage or gout. According to a study by Pession and Barbieri 1, rasburicase significantly decreased serum uric acid in all patients, with control of serum uric acid obtained in both treatment and prophylaxis groups within 24 hours of the first dose.

Key Considerations

• Rasburicase has been shown to be more effective than allopurinol in reducing uric acid levels in pediatric patients with hyperuricemia due to tumor lysis syndrome (TLS) 1.
• The use of rasburicase allows for a rapid and complete degradation of uric acid to allantoin, potentially enabling prompt continuation of chemotherapy 1.
• Allopurinol, on the other hand, can reduce the formation of uric acid but is not able to degrade it, resulting in a significant delay in the resumption of chemotherapy 1.
• Regular monitoring of uric acid levels is essential to assess treatment effectiveness and prevent potential complications.

Treatment Approach

• Rasburicase is the recommended treatment for hyperuricemia in pediatric patients, particularly those with TLS or at risk of TLS 1.
• The dose and administration schedule of rasburicase may vary depending on the patient's condition and response to treatment.
• It is essential to note that urine alkalinization is no longer recommended as a cornerstone of TLS treatment due to its potential drawbacks, including increased precipitation of calcium phosphate and reduced xanthine solubility 1.

From the FDA Drug Label

The clinical significance, if any, of these observations is unknown. Allopurinol tablets are rarely indicated for use in children with the exception of those with hyperuricemia secondary to malignancy or to certain rare inborn errors of purine metabolism Children, 6 to 10 years of age, with secondary hyperuricemia associated with malignancies may be given 300 mg allopurinol tablets daily while those under 6 years are generally given 150 mg daily.

The implications of hyperuricemia in pediatric patients are not directly addressed in the provided drug labels. However, it is mentioned that allopurinol tablets are rarely indicated for use in children, except in cases of hyperuricemia secondary to malignancy or certain rare inborn errors of purine metabolism 2. The dosage for children with secondary hyperuricemia associated with malignancies is provided, but the implications of hyperuricemia itself are not discussed 2.

From the Research

Implications of Hyperuricemia in Pediatric Patients

The implications of hyperuricemia in pediatric patients can be understood through various studies that have investigated its causes, effects, and associations with other conditions.

• Hyperuricemia is associated with an increased risk of noncommunicable diseases, such as hypertension, insulin resistance, dyslipidemia, and chronic kidney disease 3.
• Obesity is a major cause of hyperuricemia in otherwise healthy children and adolescents, and it is often accompanied by metabolic syndrome 3.
• Hyperuricemia can also be caused by chronic conditions, including Down syndrome, metabolic or genetic disease, and congenital heart disease, as well as acute conditions, such as gastroenteritis, bronchial asthma, malignant disorders, and drug side effects 3.
• In children with vesicoureteral reflux, hyperuricemia is more frequently diagnosed, and it is associated with an increased risk of urolithiasis 4.
• Elevated serum uric acid levels can blunt the antihypertensive efficacy of lifestyle modifications in children at cardiovascular risk, making it a potentially modifiable risk factor for the prevention and treatment of hypertension 5.

Mechanisms and Associations

The mechanisms underlying hyperuricemia in pediatric patients involve increased uric acid production and/or decreased uric acid excretion capacity of the kidneys and/or intestinal tract.

• Increased production of uric acid can be associated with an increase of phosphoribosyl pyrophosphate, as observed in hypoxanthine-guanine phosphoribosyltransferase deficiency 6.
• Decreased uric acid excretion from the kidneys or intestinal tract can be mediated by decreased function of the ATP-binding cassette subfamily G member 2, a urate transporter that acts in the urate secretion 6.
• Hyperuricemia is also associated with genetic disorders, such as uromodulin-associated kidney disease, which leads to tubulointerstitial damage and fibrosis, and compromised uric acid excretion capacity 6.

Treatment and Management

The treatment and management of hyperuricemia in pediatric patients involve lifestyle modifications, such as increased fluid intake, low salt and low purine diet, and urine alkalization 7.

• In children with hyperuricosuria, treatment should aim to maintain urine pH within normal values, and appropriate tests of uric acid metabolism should be performed to suspect tubular transport disturbances 7.
• Lifestyle interventions, such as increase of physical activity and dietary modifications, can improve weight status and blood pressure values, but elevated serum uric acid levels can blunt their antihypertensive efficacy 5.