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

• Tumor lysis syndrome (TLS) is seen most commonly following treatment of hematologic malignancies, such as acute lymphoblastic leukemia and Burkitt lymphoma

• Acute kidney injury

• Hyperphosphatemia (associated symptoms include nausea, vomiting, anorexia, muscle cramps, tetany, and seizures)

• Hyperkalemia (can cause arrhythmias and sudden death)

Diagnosis

• At least two of the following criteria should be observed within a 24-hour period:

  • Uric acid ≥ 8 mg/dL (≥ 476 mcmol/L)

  • Phosphate ≥ 4.5 mg/dL (≥ 1.45 mmol/L)

  • Potassium ≥ 6.0 mEq/L (≥ 6 mmol/L)

  • Corrected serum calcium ≤ 7 mg/dL (≤ 1.75 mmol/L)

  • 25% increase from baseline for these parameters

• A clinical diagnosis of TLS includes meeting the laboratory criteria and at least one clinical criterion:

  • Acute kidney injury (creatinine ≥ 1.5 × upper limit of normal or increase > 0.3 g/dL or urinary output > 0.5 mL/kg/h for 6 hours)

  • Cardiac arrhythmia

  • Sudden cardiac death

  • Seizure

Treatment

• Prevention is the most important factor in the management of TLS

• Aggressive hydration at least 24 hours prior to chemotherapy as well as 24–48 hours after chemotherapy completion

  • Helps keep urine flowing and facilitates excretion of uric acid and phosphorus

  • Maintaining a urinary output of at least 100 mL/h and a daily urine volume of at least 3 L/day is recommended

• If evidence of volume overload or inadequate urinary output develops

  • Loop diuretics can be used

  • Thiazide diuretics are contraindicated because they increase uric acid levels and can interact with allopurinol

• Allopurinol

  • Should be given to patients at moderate risk of developing TLS (eg, those with intermediate-grade lymphomas and acute leukemias) before starting chemotherapy

  • Dose should be reduced in patients with impaired kidney function

• Rasburicase

  • Should be given intravenously to patients at high risk for developing TLS (eg, those with high-grade lymphomas or acute leukemias with markedly elevated WBC counts)

  • May also be considered for patients with baseline elevated uric acid who are being treated with venetoclax for chronic lymphocytic leukemia or in any patient in whom uric acid levels reach levels > 8 mg/dL despite treatment with allopurinol

  • Cannot be given to patients with known glucose 6-phosphate dehydrogenase deficiency or to pregnant or lactating women