What is the recommended approach for urinary alkalinization in patients at risk of tumor lysis syndrome (TLS)?

Urinary Alkalinization for Tumor Lysis Syndrome (TLS)

Urinary alkalinization is currently not recommended for the prevention or treatment of tumor lysis syndrome due to lack of clear evidence demonstrating benefit and potential complications including calcium phosphate precipitation. 1

Current Recommendations on Urinary Alkalinization

• Historically, sodium bicarbonate was recommended as part of TLS prevention and management strategies, particularly when using allopurinol, but this practice is no longer supported by evidence 1
• The solubility of uric acid increases from approximately 15 mg/dL at pH 5.0 to approximately 200 mg/dL at pH 7.0, which was the original rationale for alkalinization 1
• Despite increasing uric acid solubility, alkalinization does not substantially increase the solubility of xanthine and hypoxanthine, which can be problematic in patients treated with allopurinol 1
• Xanthine has particularly low solubility (5 mg/dL at pH 5.0 and only 13 mg/dL at pH 7.0), which can lead to xanthine crystal precipitation in renal tubules 1

Evidence Against Routine Alkalinization

• Animal studies have shown that increasing urine flow rate is more effective than alkalinization for preventing urate-induced obstructive uropathy 1
• In the absence of increased urine output, increasing urinary pH greater than 7.0 was ineffective in preventing uric acid crystallization 1
• Potential complications of alkalinization include:
  • Metabolic alkalosis 1
  • Calcium phosphate precipitation (particularly problematic in TLS where hyperphosphatemia is common) 1
  • Xanthine-obstructive uropathies in patients treated with allopurinol 1

Specific Situations Where Alkalinization May Be Considered

• The consensus of expert panels is that alkalinization is only indicated for patients with metabolic acidosis, in which case sodium bicarbonate may be considered based on institutional standards 1
• No consensus exists among experts regarding alkalinization for patients receiving allopurinol treatment 1
• Alkalinization is specifically not required in patients receiving rasburicase 1

Preferred Approach for TLS Prevention and Management

• Aggressive hydration and diuresis are the fundamental strategies for TLS prevention and management 1
• Pediatric patients should receive 2-3 L/m²/day (or 200 mL/kg/day if <10 kg) of IV fluids, typically one-quarter normal saline/5% dextrose 1
• Maintain urine output within 80-100 mL/m²/h (4-6 mL/kg/h if <10 kg) 1
• Diuretics may be used to maintain adequate output if there is no evidence of acute obstructive uropathy or hypovolemia 1
• For hyperuricemia management:
  • Allopurinol (xanthine oxidase inhibitor) for intermediate-risk patients 1
  • Rasburicase (recombinant urate oxidase) for high-risk patients or those with established hyperuricemia 2

Monitoring Recommendations

• Urine-specific gravity should be monitored and maintained at 1.010 1
• Regular assessment of serum electrolytes, particularly potassium, phosphate, and calcium 2
• Monitor urine pH, but do not target alkalinization unless specifically indicated 1
• Monitor fluid balance and renal function closely 1

Common Pitfalls to Avoid

• Initiating alkalinization without considering the risk of calcium phosphate precipitation, especially in patients with hyperphosphatemia 1
• Using alkalinization in patients receiving rasburicase (not necessary and potentially harmful) 1
• Focusing on alkalinization rather than adequate hydration and urine flow, which are more important for preventing uric acid nephropathy 1
• Failing to withhold potassium, calcium, and phosphate from initial hydration fluids due to the concurrent risks in TLS 1