Hyperuricemia & Tumor Lysis Syndrome

Key Features

• Complication of treatment-associated tumor lysis of hematologic as well as rapidly proliferating malignancies

• May be worsened by thiazide diuretic use

• Rapid increase in serum uric acid can cause acute urate nephropathy from uric acid crystallization

• To prevent urate nephropathy, serum uric acid must be reduced before chemotherapy

Clinical Findings

• Acute kidney injury

• Hyperuricemia

• Hyperphosphatemia (associated symptoms include nausea, vomiting, seizures)

• Hyperkalemia (can cause arrhythmias and sudden death)

Diagnosis

• Laboratory tests (serum uric acid, phosphorus, calcium, electrolytes [particularly, potassium and sodium], creatinine) should be monitored following initiation of chemotherapy

Treatment

• Prevention of hyperuricemia, hyperphosphatemia and hyperkalemia are most important

  • The American Society of Clinical Oncology guidelines recommend aggressive hydration before, during, and after chemotherapy to help keep urine flowing and facilitate excretion of uric acid and phosphorus

  • Bicarbonate infusions are no longer recommended

• Treatment for hyperuricemia

  • Allopurinol

    • Blocks the enzyme xanthine oxidase and therefore the formation of uric acid from purine breakdown

    • Dosage: 100 mg/m² every 8 hours orally (maximum 800 mg/day) with dose adjustments for impaired kidney function given before starting chemotherapy

  • Rasburicase

    • Dosage: 0.1–0.2 mg/kg/day intravenously for 1–7 days

    • Indicated for patients at high risk for developing tumor lysis syndrome or in whom hyperuricemia develops despite treatment with allopurinol

    • May be considered for patients with baseline elevated uric acid who are being treated with venetoclax (Bcl-2 inhibitor) for chronic lymphocytic leukemia who have large lymph nodes [≥ 10 cm] or nodes ≥ 5 cm accompanied by white blood cell counts > 25,000/mcL [25 × 10⁹/L]

    • Cannot be given to patients with known glucose 6-phosphate dehydrogenase (G6PD) deficiency nor can it be given to pregnant or lactating women

• Elevated potassium or phosphorus levels need to be promptly treated (see Hyperkalemia and Hyperphosphatemia)