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.
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. Acute kidney injury may then develop from the crystallization and deposition of uric acid and calcium phosphate within the renal tubules further exacerbating the hyperphosphatemia and hyperkalemia.
Symptoms of hyperphosphatemia include nausea and vomiting as well as seizures. Also, with high levels of phosphorus, 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.
Prevention is the most important factor in the management of TLS. Aggressive hydration prior to initiation of chemotherapy as well as during and after completion of the chemotherapy helps keep urine flowing and facilitates excretion of uric acid and phosphorus. In addition, for patients at moderate risk for developing TLS, eg, those with intermediate-grade lymphomas and acute leukemias, allopurinol should be given before starting chemotherapy at an oral dose of 100 mg/m2 every 8 hours (maximum 800 mg/day) with dose reductions for impaired kidney function. Rasburicase 0.1–0.2 mg/kg/day is given intravenously for 1–7 days to patients at high risk for developing TLS, eg, those with high-grade lymphomas or acute leukemias with markedly elevated white blood cell counts (acute myeloid leukemia, white blood cell count greater than 50,000/mcL [50,000/109/L] or acute lymphoblastic leukemia, white blood cell count greater than 100,000/mcL [100,000/109/L]). Rasburicase 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 larger) or nodes 5 cm or larger accompanied by white blood cell counts greater than 25,000/mcL (25,000/109/L); or in any patient in whom hyperuricemia develops despite treatment with allopurinol. Rasburicase cannot be given to patients with known glucose 6-phosphate dehydrogenase (G6PD) deficiency nor can it be given to pregnant or lactating women. Systemic bicarbonate infusions to alkalinize the urine are not routinely recommended unless there is accompanying metabolic acidosis. In addition to the hyperuricemia, laboratory values should be monitored following initiation of chemotherapy; elevated potassium or phosphorus levels need to be promptly managed.