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ESSENTIALS OF DIAGNOSIS

ESSENTIALS OF DIAGNOSIS

  • Complication of treatment-associated tumor lysis of hematologic and rapidly proliferating malignancies.

  • May be worsened by thiazide diuretics.

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

  • Reducing pre-chemotherapy serum uric acid is fundamental to preventing urate nephropathy.

GENERAL CONSIDERATIONS

Tumor lysis syndrome (TLS) is seen most commonly following treatment of hematologic malignancies such as acute lymphoblastic leukemia and Burkitt lymphoma. However, TLS can develop from any tumor highly sensitive to chemotherapy. TLS is caused by the massive release of cellular material including nucleic acids, proteins, phosphorus, and potassium. If both the metabolism and excretion of these breakdown products are impaired, hyperuricemia, hyperphosphatemia, and hyperkalemia will develop abruptly. AKI may then develop from the crystallization and deposition of uric acid and calcium phosphate within the renal tubules, further exacerbating the hyperphosphatemia and hyperkalemia.

CLINICAL FINDINGS

A. Symptoms and Signs

Symptoms of hyperphosphatemia include nausea, vomiting, anorexia, muscle cramps, tetany, and seizures. High levels of phosphorus and co-precipitation with calcium can cause renal tubule blockage, further exacerbating the kidney injury. Hyperkalemia, due to release of intracellular potassium and impaired kidney excretion, can cause arrhythmias and sudden death.

B. Laboratory Findings

The laboratory diagnosis of TLS include at least two of the following criteria observed within a 24-hour period: uric acid 8 mg/dL or higher (476 mcmol/L or higher), phosphate 4.5 mg/dL or higher (1.45 mmol/L or higher), potassium 6.0 mEq/L or more (6 mmol/L or more) (or a 25% increase from baseline for these parameters), and corrected serum calcium 7 mg/dL or lower (1.75 mmol/L or lower). A clinical diagnosis of TLS includes meeting the laboratory criteria and at least one clinical criterion: AKI (creatinine greater than or equal to 1.5 × upper limit of normal or increase greater than 0.3 g/dL or urinary output greater than 0.5 mL/kg/hour for 6 hours) or cardiac arrhythmia, sudden cardiac death, or 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. It is recommended to maintain a urinary output of at least 100 mL/hour, and a daily urine volume of at least 3 L/day. 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. For patients at moderate risk of developing TLS, eg, those with intermediate-grade lymphomas and acute leukemias, allopurinol should be given before starting chemotherapy with dose reductions for impaired kidney function. Rasburicase is given intravenously to patients at high risk for developing ...

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