Patients who have a malignancy with a high tumor burden (eg, chronic lymphocytic leukemia) or a rapid cell turnover rate are at risk for tumor lysis syndrome (TLS) with the initiation of cytotoxic chemotherapy or immunotherapy.  TLS is caused by the massive release of intracellular contents into the circulation due to widespread tumor cell death.  It is generally marked by significant electrolyte abnormalities (eg, hyperkalemia) and acute kidney injury, which is due to the following:

• Hyperuricemia:  Lysed tumor cells release purine nucleic acids into the circulation, which are subsequently metabolized by xanthine oxidase into uric acid.  Because uric acid is poorly soluble in the renal tubules and collecting system, it precipitates into obstructing urate crystals.

• Hyperphosphatemia:  Phosphate levels in tumor cells are up to 3 times higher than in normal cells.  Therefore, widespread tumor cell lysis is usually associated with hyperphosphatemia.  Phosphate is subsequently excreted into the renal tubules and collecting system, where it binds to calcium and causes obstructing calcium-phosphate stones.

TLS prophylaxis generally includes a normal saline infusion to flush the renal system and prevent crystal deposition and an agent (eg, allopurinol, rasburicase) to reduce systemic uric acid levels.

(Choice A)  Calcitonin increases renal excretion of calcium and decreases bone resorption by inhibiting osteoclasts.  It is used primarily for severe hypercalcemia (eg, due to hypercalcemia of malignancy).

(Choice B)  Leucovorin is administered in patients receiving methotrexate (eg, some leukemias) or other folic acid antagonists to prevent adverse events from damage to rapidly dividing cells in the gastrointestinal system and liver.

(Choice C)  N-acetylcysteine, an antioxidant precursor to glutathione, is used primarily for acetaminophen poisoning and acute liver failure.

(Choice E)  Sodium bicarbonate alkalinizes the urine.  Although uric acid is more likely to precipitate in acidic urinary environments, studies have shown that urinary alkalization does not reduce the risk of kidney injury in TLS.  It is generally reserved for patients with TLS who have severe metabolic acidosis.

Educational objective:
Patients who undergo initial cytotoxic chemotherapy or immunotherapy for hematologic malignancies with high tumor burden or rapid division rate are at risk for tumor lysis syndrome due to the massive release of intracellular tumor products into the circulation.  Major manifestations include electrolyte abnormalities and renal insufficiency due to the precipitation of uric acid and calcium-phosphate.  Renal injury can often be prevented with intravenous fluids to flush the kidneys and uric acid inhibitors to reduce serum uric acid levels.