Tumor lysis syndrome refers to the constellation of metabolic disturbances that may follow the initiation of cancer treatment. [1, 2, 3] It usually occurs in patients with bulky, rapidly proliferating, treatment-responsive tumors. (See Pathophysiology and Etiology.) 
Although tumor lysis syndrome has been reported with virtually every type of tumor, it is typically associated with acute leukemias and high-grade non-Hodgkin lymphomas,  such as Burkitt lymphoma. [6, 7] The syndrome has also been reported with other hematologic malignancies and with solid tumors such as hepatoblastoma and stage IV neuroblastoma. [8, 9] Tumor lysis syndrome arises most commonly in the setting of initial chemotherapeutic treatment, but spontaneous cases have increasingly been documented in patients with high-grade hematologic malignancies. 
A potentially lethal complication of anticancer treatment,  tumor lysis syndrome occurs when large numbers of neoplastic cells are killed rapidly, leading to the release of intracellular ions and metabolic byproducts into the systemic circulation. Clinically, the syndrome is characterized by rapid development of hyperuricemia,  hyperkalemia, hyperphosphatemia, hypocalcemia, and acute renal failure. (See Pathophysiology, Etiology, Prognosis, Presentation, and Workup.) 
The main principles of tumor lysis syndrome management are (1) identification of high-risk patients with initiation of preventive therapy and (2) early recognition of metabolic and renal complications and the prompt administration of supportive care, including hemodialysis. (See Prognosis, Treatment, and Medication.)
Rapid tumor cell turnover results in release of intracellular contents into the circulation. This release can inundate renal elimination and cellular buffering mechanisms, leading to numerous metabolic derangements.
Clinically significant tumor lysis syndrome can occur spontaneously, but it is most often seen 48-72 hours after initiation of cancer treatment. Hyperkalemia is often the earliest laboratory manifestation. Hyperkalemia and hyperphosphatemia result directly from rapid cell lysis.
Hypocalcemia is a consequence of acute hyperphosphatemia with subsequent precipitation of calcium phosphate in soft tissues. In acute kidney injury, decreased calcitriol levels also cause hypocalcemia.
Uric acid is the terminal catabolic product of purine metabolism in humans. Nucleic acid purines, which are released by cell breakdown, are ultimately metabolized to uric acid by hepatic xanthine oxidase. This conversion leads to hyperuricemia.
Uric acid is a weak acid with a pKa of approximately 5.4. It is soluble in plasma and is freely filtered at the renal glomeruli. However, uric acid is less soluble in renal tubular and collecting duct fluid due to normally acidic media, thus increasing the possibility of uric acid crystal formation in cases of hyperuricemia.
Acute kidney injury
The kidney is the primary organ involved in the clearance of uric acid, potassium, and phosphate. Preexisting volume depletion or renal dysfunction predisposes patients to worsening metabolic derangements and acute kidney injury (AKI). The AKI is often oliguric and can be multifactorial in etiology.
Uric acid nephropathy, however, is the major cause of AKI. Its development is due to mechanical obstruction by uric acid crystals in the renal tubules. Uric acid has a pKa of 5.6; uric acid precipitation is enhanced by high acidity and high concentration in the renal tubular fluid, and uric acid becomes less soluble as renal tubule pH decreases. Renal medullary hemoconcentration and decreased tubular flow rate also contribute to crystallization. 
Another cause of AKI is acute nephrocalcinosis from calcium phosphate crystal precipitation, which may occur in other tissues. This develops in the setting of hyperphosphatemia and is exacerbated by overzealous iatrogenic alkalinization, because calcium phosphate, unlike uric acid, becomes less soluble at an alkaline pH. Precipitation of xanthine, which is even less soluble in urine than uric acid, or other purine metabolites whose urinary excretion is increased by the use of allopurinol, are other causes of AKI.
Tumor lysis syndrome occurs most often in patients with acute leukemia with high white blood cell (WBC) counts and in those with high-grade lymphomas in response to aggressive treatment. Tumor lysis syndrome may also occur in other hematologic malignancies and in a variety of solid tumors such as hepatoblastoma and stage IV neuroblastoma. [8, 9] It has occasionally occurred spontaneously, prior to any form of therapy. 
Patients at highest risk are those with bulky, rapidly proliferating tumors that are sensitive to treatment. An elevated pretreatment lactate dehydrogenase level, which correlates with high tumor volume, is a strong prognostic indicator for developing clinically significant complications of therapy. The presence of renal insufficiency prior to therapy also correlates with an increased likelihood of tumor lysis syndrome.
Reports exist of tumor lysis syndrome associated with the administration of radiation therapy,  corticosteroids, hormonal agents, biologic response modifiers, and monoclonal antibodies. Agents reported to cause tumor lysis syndrome include the following:
The development of tumor lysis syndrome is not limited to the systemic administration of agents; it can occur with intrathecal administration of chemotherapy and with chemo-embolization.
Rare clinical situations in which tumor lysis syndrome has been observed  include pregnancy and fever. Patients under general anesthesia have also experienced tumor lysis syndrome.
The incidence of tumor lysis syndrome is unknown. The prevalence varies among different malignancies; bulky, aggressive, treatment-sensitive tumors are associated with higher frequencies of tumor lysis syndrome. In studies of frequency in patients with intermediate-grade or high-grade non-Hodgkin lymphomas, laboratory evidence of tumor lysis syndrome (42%) occurred much more frequently than the symptomatic clinical syndrome (6%). In children with acute leukemia receiving induction chemotherapy, silent laboratory evidence of tumor lysis syndrome occurred in 70% of cases, but clinically significant tumor lysis syndrome occurred in only 3% of cases.
As advances are made in cancer treatment and as high-dose regimens become more commonplace, tumor lysis syndrome incidence may increase and the syndrome may emerge in a broader spectrum of malignancies.
Although tumor lysis syndrome occurs in all age groups, advanced age leading to impaired renal function may predispose patients to clinically significant tumor lysis syndrome owing to a decreased ability to dispose of tumor lysis byproducts.
Early recognition of signs and symptoms of patients at risk for tumor lysis syndrome, including identification of abnormal clinical and laboratory values, can lead to successful prevention of the otherwise life-threatening complications of the condition.
Potential complications of tumor lysis syndrome include uremia and oliguric renal failure due to tubule precipitation of uric acid, calcium phosphate, or hypoxanthine.
Severe electrolyte disturbances, such as hyperkalemia and hypocalcemia, predispose patients to cardiac arrhythmia and seizures.
Iatrogenic complications, such as pulmonary edema from overly vigorous hydration or metabolic alkalosis from excess exogenous administration of bicarbonate, can also occur and are life threatening if not immediately addressed.
Acute kidney injury
Renal tubule precipitation of uric acid, calcium phosphate, or hypoxanthine causes acute kidney injury. This is often oliguric (<400 mL daily) in nature, leading to volume overload and complications of hypertension and pulmonary edema.
High blood urea nitrogen (BUN) levels due to increased protein catabolism and renal impairment can be severe enough to result in pericarditis, platelet dysfunction, and defective cellular immunity. Renal dysfunction can be severe enough to require dialysis, but with prompt supportive measures, it is usually reversible.
Hyperkalemia can lead to electrocardiographic changes and life-threatening cardiac arrhythmia, including asystole. Severe potassium elevation can cause electrocardiographic alterations such as peaked T waves, flattened P waves, prolonged PR interval, widened QRS complexes, deep S wave, and sine waves. Hypocalcemia can lead to QT interval lengthening, which predisposes patients to ventricular arrhythmia.
Acute kidney injury and the liberation of large amounts of endogenous intracellular acids from cellular catabolism result in acidemia. This acidemia causes a decrease in serum bicarbonate concentration and a high anion gap acidosis (see the Anion Gap calculator).
Acidemic states can worsen the many electrolyte imbalances already present in tumor lysis syndrome; intracellular uptake of potassium is hindered, uric acid solubility is decreased, and extracellular shift of phosphate is promoted. Calcium phosphate solubility, however, improves in acidic conditions.
The myriad of metabolic disorders must be assessed and treated rapidly. Proper fluid management, alkalinization of the urine, correction of acidosis, and attention to infections are the mainstays of therapy.
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