It is caused by massive lysis of malignant cells and leads to release of large amounts of potassium, phosphate and uric acid into the systemic circulation with secondary hypocalcemia. Acute kidney injury can result from precipitation of uric acid and/or calcium phosphate in the renal tubules.
Most commonly encountered after initial chemotherapy for
a) High grade lymphomas (particularly Burkitt subtype)
b) Acute lymphoblastic leukemia (mature B cell acute lymphoblastic leukemia)
c) May occur spontaneously in high grade lymphoma or ALL
d) May occur in other tumor types with a high proliferative rate, large tumor burden or high sensitivity to cytotoxic therapy.
Diagnosis: Cairo-Bishop Definition of TLS
Laboratory tumor lysis syndrome is defined as any 2 or more of the following metablic abnormalities and presents within 3 days before or 7 days after instituting chemotherapy.
a) Uric acid > 476 micromol/L or 25% increase from baseline
b) Potassium > 6 mmol/L or 25% increase from baseline
c) Phosphate > 1.45 mmol/L in adults (> 2.1 in children) or 25% increase from baseline
d) Calcium < 1.75 mmol/L or 25% decrease from baseline
Clinical TLS: is defined as laboratory TLS plus one or more of the following that was not directly or probably attributable to a therapeutic agent
a) Increased serum creatinine > 1.5 from the upper limit normal
b) Cardiac arrythmias/sudden death
c) Seizure
Treatment
Best management is prevention
1. Key components are
a) Aggressive fluid hydration prior to therapy in all patients at intermediat or high risk for TLS. Children and adult should initally receive 2 to 3 L/m2 per day of IV fluid (or 200ml/kg per day in children weighing less than 10 kg). Urine output should be monitored closely and maintained within a range of 80 to 100 ml/m2 per hour (2 ml/kg for both children and adults, 4-6ml/kg in children less than 10 kg). Diuretics can be used to maintain the urine output, if necessary but should not be required in patients with relatively normal renal and cardiac function.
b) Diuresis
c) Administration of hypouricemic agents
Purine catabolism results in the production of hypoxanthine and xanthine which are metabolized to uric acid via the enzymatic action of xanthine oxidase. Allopurinol inhibits xanthine oxidase: blocking hypoxanthine and xanthine to uric acid. After two to three days, allopurinol therapy results in increased excretion of both hypoxanthine which is more soluble than uric acid and xanthine which is less soluble than uric acid. A marked increase in xanthine excretion can occur when allopurinol is given for prevention of TLS and may lead to acute renal failure or xanthine stones. Allopurinol does not reduce the serum uric acid concentration before treatment is initiated. Thus for patients with pre-existing hyperuricemia, rasburicase is the preferred hypouricemic agent. Urate oxidase (which in not present in human) oxidizes preformed uric acid to allantoin which is 5 to 10 times more soluble than uric acidin acid urine. When exogenous urate oxidase (rasburicase) is administered, serum and urinary uric acid levels decrease markedly within approximtely four hours.
d) Urinary alkalinazion: generally not recommended. Benefit in increasing uric acid excretion is unproven. Potential harms, particularly in the setting of hyperphosphatemia.
e) Indications for dialysis are oliguria, persistent hyperuricemia, hyperphosphatemia and hypocalcemia.
Indications for renal replacement therapy include:
-Severe oliguria and anuria
-Persistent hyperkalemia
-Hyperphosphatemia induced symptomatic hypocalcemia
