What is the management of hyperuricemia in pediatric patients?

Management of Hyperuricemia in Pediatric Patients

The management of hyperuricemia in pediatric patients should focus on adequate hydration as the mainstay of treatment, with risk-stratified use of allopurinol for intermediate-risk patients and rasburicase for high-risk patients, particularly those with tumor lysis syndrome. 1

Risk Assessment and Initial Management

High-Risk Patients

• Patients with malignancies at high risk for tumor lysis syndrome (TLS):
  • Aggressive hydration (2-3 L/m²/day or 200 mL/kg/day if <10 kg) 1
  • Rasburicase administration (0.15-0.20 mg/kg/day IV) 1, 2
  • Admission to intensive care unit or closely monitored setting 1
  • Notification of renal specialist for potential dialysis 1

Intermediate-Risk Patients

• Patients with moderate risk of hyperuricemia/TLS:
  • Aggressive hydration 1
  • Allopurinol at 50-100 mg/m² every 8 hours orally (maximum 300 mg/m²/day) or 10 mg/kg/day divided every 8 hours (maximum 800 mg/day) 1
  • For patients unable to take oral medication: IV allopurinol at 200-400 mg/m²/day in 1-3 divided doses (maximum 600 mg/day) 1
  • Consider single dose of rasburicase in select cases 1

Low-Risk Patients

• Close monitoring with watch-and-wait approach 1
• Maintain adequate hydration 1

Specific Medication Considerations

Allopurinol

• Dosing adjustments for renal impairment:

  • Creatinine clearance 10-20 mL/min: 200 mg/day
  • Creatinine clearance <10 mL/min: ≤100 mg/day
  • Extreme renal impairment (clearance <3 mL/min): extended dosing interval 3

• Important precautions:

  • Monitor for hypersensitivity reactions, especially in patients with HLA-B*58:01 genetic variant 4
  • Reduce doses of azathioprine and 6-mercaptopurine by 65-75% when used concurrently 1, 4
  • Regular monitoring of complete blood counts, renal function, and liver function tests 4

Rasburicase

• Contraindications:

  • G6PD deficiency
  • History of anaphylaxis/hypersensitivity reactions
  • History of hemolytic reactions or methemoglobinemia 1

• Administration:

  • Intravenously over 30 minutes
  • Blood samples for uric acid monitoring must be placed immediately on ice 1
  • Highly effective in rapidly reducing uric acid levels (93-100% response rate) 2

Hydration and Monitoring

• Target urine output: 80-100 mL/m²/hour (4-6 mL/kg/hour if <10 kg) 1
• Monitor:
  • Urine-specific gravity (maintain at ≤1.010) 1
  • Serum uric acid levels
  • Electrolytes (potassium, phosphate, calcium)
  • Renal function

Important Considerations

• Avoid alkalinization: No longer recommended due to lack of evidence and potential complications (calcium phosphate precipitation, reduced xanthine solubility) 1

• Calcium administration: Not recommended for mild hypocalcemia due to risk of calcium phosphate precipitation; only use for hyperkalemia-induced cardiac arrhythmias 1

• Comorbidities: Hyperuricemia in pediatric patients is associated with hypertension, obesity, and albuminuria in those with chronic kidney disease 5

Special Situations

• For prevention of uric acid nephropathy during neoplastic disease therapy:

  • Allopurinol 600-800 mg daily for 2-3 days with high fluid intake 3

• For children with secondary hyperuricemia associated with malignancies:

  • Ages 6-10 years: 300 mg allopurinol daily
  • Under 6 years: 150 mg allopurinol daily
  • Evaluate response after 48 hours and adjust dosage if necessary 3

The evidence strongly supports that early intervention with appropriate hydration and antihyperuricemic therapy significantly reduces morbidity and mortality in pediatric patients with hyperuricemia, particularly in those at risk for TLS 1.