In a case of Tumor Lysis Syndrome (TLS) with impaired renal function, what important drug should be given in addition to hydration?

Rasburicase in Addition to Hydration for Tumor Lysis Syndrome with Decreased Urine Output

In a patient with established Tumor Lysis Syndrome following chemotherapy who has decreased urinary output, rasburicase (Option D) is the critical drug to administer in addition to hydration, as it rapidly degrades existing uric acid to prevent further renal injury and can reverse renal insufficiency. 1

Why Rasburicase is Essential in This Clinical Scenario

Immediate Mechanism of Action

• Rasburicase converts existing uric acid to allantoin within 4 hours, achieving a median decrease of 9.1 mg/dL in hyperuricemic patients, which is critical when renal function is already compromised 2
• Unlike allopurinol (which only prevents new uric acid formation), rasburicase actively degrades pre-existing elevated uric acid levels, making it superior when TLS has already developed 3, 4
• The drug allows for rapid reduction of uric acid crystallization in renal tubules, which is the primary mechanism causing the decreased urinary output 1, 5

Guideline-Based Recommendations for Established TLS

• The European Hematology Association mandates that all patients with clinical TLS receive rasburicase and hydration through central venous access 1, 6
• Clinical TLS (which includes decreased urine output as a manifestation of renal injury) requires rasburicase regardless of which specific metabolic abnormalities are present 6
• The standard dose is 0.20 mg/kg/day infused over 30 minutes for 3-5 days 1, 7

Role of Loop Diuretics (Lasix) - A Critical Caveat

When Loop Diuretics Are Appropriate

• Loop diuretics may be required to maintain target urine output (≥100 mL/hour in adults) ONLY after ensuring adequate hydration status 1
• The hemodynamic status and hydration level must be verified before using loop diuretics 1

When Loop Diuretics Are Contraindicated

• Loop diuretics are contraindicated in patients with hypovolemia or obstructive uropathy, both of which can present with decreased urine output 1, 7
• Measurement of urine osmolality and fractional excretion of sodium helps define true hydration status before considering diuretics 1
• In the setting of established TLS with renal injury, aggressive hydration with rasburicase takes priority over diuretics 1, 7

Why Other Options Are Incorrect

Thiazide Diuretics (Option B)

• Thiazide diuretics have no role in TLS management and are not mentioned in any guidelines for this indication 1, 7
• They are less effective than loop diuretics for achieving high urine output and can worsen electrolyte abnormalities 7

Lasix Alone (Option A)

• While loop diuretics may be adjunctive, rasburicase is the definitive treatment that addresses the underlying pathophysiology of uric acid nephropathy causing the decreased output 1
• Studies show only 0.4-1.7% of patients given rasburicase required dialysis compared to 20% given allopurinol alone, demonstrating rasburicase's ability to reverse renal insufficiency 5, 3

Clinical Evidence Supporting Rasburicase

Efficacy in Renal Protection

• In randomized trials, rasburicase achieved 87% response rate (uric acid ≤7.5 mg/dL) compared to 66% with allopurinol (p=0.0009) 2
• Rasburicase can reverse renal insufficiency and avoid dialysis in patients with established TLS 5, 3
• Clinical TLS occurred in only 3% of rasburicase-treated patients versus 4% with allopurinol alone 2

Rapid Onset Critical for Renal Salvage

• Among patients with baseline uric acid ≥8 mg/dL, 72% achieved control by 4 hours, 92% by 48 hours, and 100% by 96 hours 2
• This rapid action is essential when renal function is already compromised, as delayed treatment increases risk of irreversible renal failure 5, 8

Important Contraindications to Screen For

Before administering rasburicase, verify the patient does not have:

• G6PD deficiency (causes hemolytic anemia) 1, 7
• Methemoglobinemia or other metabolic disorders predisposing to hemolysis 1
• In these patients, use allopurinol with hydration and urine alkalinization instead 1

Concurrent Management Considerations

Do Not Combine with Allopurinol

• Never administer allopurinol concurrently with rasburicase, as this causes xanthine accumulation and removes substrate for rasburicase 1, 6, 7
• Start allopurinol only after completing the rasburicase course 1

Avoid Urine Alkalinization with Rasburicase

• Urine alkalinization is not recommended when using rasburicase, as it increases calcium phosphate precipitation risk without added benefit 1, 7

Monitoring Requirements

• Monitor vital signs, urine output, serum uric acid, electrolytes, and renal function every 6 hours for the first 24 hours 1, 7
• Continuous ECG monitoring is mandatory if hyperkalemia is present 1, 7

When to Consider Dialysis

Indications for urgent renal replacement therapy include: 7

• Severe oliguria or anuria despite rasburicase and hydration
• Persistent life-threatening hyperkalemia
• Hyperphosphatemia with symptomatic hypocalcemia
• Hyperuricemia not responding to rasburicase
• Severe volume overload