What medication should be given to a patient (Pt) with lymphoma presenting with decreased urine output after chemotherapy?

Management of Lymphoma Patient with Decreased Urine Output After Chemotherapy

The correct answer is B - Allopurinol, as this patient is presenting with tumor lysis syndrome (TLS), and allopurinol is the appropriate agent for preventing further uric acid formation and renal crystallization in this clinical scenario. 1

Understanding the Clinical Scenario

This patient with lymphoma presenting with decreased urine output after chemotherapy is experiencing tumor lysis syndrome (TLS), a metabolic emergency characterized by massive tumor cell breakdown releasing intracellular contents into the bloodstream. 1, 2

• The decreased urine output signals potential acute kidney injury from uric acid crystallization in renal tubules, hyperkalemia, hyperphosphatemia, and hypocalcemia. 1, 3
• Lymphomas, particularly high-grade and bulky disease, carry high TLS risk due to rapid cell turnover and chemotherapy sensitivity. 4

Why Allopurinol is the Correct Choice

Allopurinol blocks xanthine oxidase enzyme activity in the liver, preventing conversion of xanthine and hypoxanthine to uric acid, thereby decreasing the risk of further uric acid crystallization in the kidneys. 4

• For patients already presenting with TLS manifestations (like decreased urine output), allopurinol prevents additional uric acid formation while aggressive hydration and supportive measures address existing metabolic derangements. 1
• The consensus guidelines recommend allopurinol at 100 mg/m² every 8 hours orally (maximum 800 mg/day) or 200-400 mg/m²/day IV in divided doses (maximum 600 mg/day). 4

Why Not the Other Options

Thiazide diuretics (Option A) are contraindicated because they can worsen hyperuricemia and are inappropriate for managing TLS-related oliguria. 2

Beta blockers (Option C) have no role in TLS management and do not address the underlying metabolic crisis. 1, 2

Critical Management Algorithm

Immediate Actions Required:

1. Aggressive IV hydration with 3L/m² to maintain urine output ≥100 mL/hour in adults (3 mL/kg/hour in children <10 kg). 1, 2

2. Loop diuretics (not thiazides) may be required to achieve target urine output, except in obstructive uropathy or hypovolemia. 1, 2

3. Start allopurinol immediately to prevent further uric acid formation. 1, 4

4. Consider rasburicase if this patient has severe hyperuricemia (>8 mg/dL) or worsening renal function, as rasburicase degrades existing uric acid to allantoin (5-10 times more soluble). 1, 5

Monitoring Requirements:

• Check uric acid, electrolytes (potassium, phosphate, calcium), creatinine, and BUN every 6 hours for the first 24 hours, then every 12 hours for 3 days. 2
• Maintain urine output monitoring hourly. 1, 2

Important Caveats and Pitfalls

Never administer allopurinol concurrently with rasburicase - this causes dangerous xanthine accumulation, as allopurinol blocks xanthine oxidase while rasburicase degrades uric acid, leaving xanthine to crystallize in renal tubules. 4, 6

• If rasburicase is used first, wait to start allopurinol until after completing the 3-5 day rasburicase course. 1, 4

Dose reduction is critical in renal impairment - reduce allopurinol by 50% or more when creatinine is elevated, as the drug and its metabolites accumulate renally. 4

Xanthine nephropathy risk - allopurinol increases xanthine and hypoxanthine levels, which have lower solubility than uric acid and can cause xanthine crystal deposition in renal tubules, particularly at high tumor burden. 4, 7

• Despite allopurinol use, urinary xanthine concentration exceeded solubility in 55% of lymphoma patients post-chemotherapy, with three developing transient renal failure. 7

When Rasburicase Becomes Preferred

High-risk patients should receive rasburicase instead of allopurinol as primary therapy, including those with: 4

• Pre-existing renal impairment (like this patient with decreased urine output)
• Hyperuricemia >8 mg/dL
• Bulky lymphoma disease
• Obstructive uropathy

In pediatric studies, only 2.6% of patients receiving rasburicase required dialysis compared to 16% receiving allopurinol. 4, 5

• Rasburicase achieved 86% reduction in plasma uric acid within 4 hours versus only 12% with allopurinol. 5

However, rasburicase is contraindicated in G6PD deficiency, pregnancy, lactation, and history of anaphylaxis or methemoglobinemia. 4, 8