Hyperuricemia

Compared with hypercalcemia, hyperuricemia is a less common metabolic emergency in adult cancer patients.

Etiology and Risk Factors

Hyperuricemia occurs most often in patients with hematologic disorders, particularly leukemias, high-grade lymphomas, and myeloproliferative diseases (polycythemia vera). It may occur secondary to treatment of the malignancy.

Drugs

Hyperuricemia is also associated with certain cytotoxic agents (eg, tiazofurin and aminothiadiazoles). Various other drugs can contribute to hyperuricemia by increasing uric acid production or decreasing its excretion. Diuretics (thiazides, furosemide, and ethacrynic acid [Edecrin]) cause acute uricosuria, and hyperuricemia may occur secondary to volume contraction. Antituberculous drugs, such as pyrazinamide and ethambutol, as well as nicotinic acid (niacin) are also associated with hyperuricemia.

Extensive or aggressive tumors

Patients with extensive, anaplastic, or rapidly proliferating tumors are at greatest risk for hyperuricemia. These include patients with bulky lymphomas and sarcomas, those with chronic myelocytic leukemia or chronic lymphocytic leukemia and extreme leukocytosis, and those undergoing remission-induction chemotherapy for acute leukemia.

Renal impairment

Individuals with preexisting renal impairment are also at risk for becoming hyperuricemic.

Signs and Symptoms

Patients with clinical syndromes caused by hyperuricemia present with significant elevations of serum uric acid levels. Gouty arthritis may be seen occasionally, but the most significant complication is renal dysfunction, particularly acute renal failure. Clinical symptoms associated with renal dysfunction vary depending on the degree of dysfunction and the timing of its development. In patients with acute renal failure, clinical symptoms may include abnormal mental status, nausea and vomiting, fluid overload, pericarditis, and seizures.

Diagnosis

The diagnosis of hyperuricemia is based on laboratory findings of high serum uric acid levels, hyperuricosuria, and increased serum creatinine and urea nitrogen levels.

Prognosis

Prognosis often depends on the etiology of the hyperuricemia.

Treatment

Prophylactic measures

Prophylactic measures against the development of hyperuricemia should be undertaken before initiation of chemotherapy. Drugs that increase serum urate levels or produce acidic urine (eg, thiazides and salicylates) should be discontinued if possible. Alkalinization of the urine should be initiated to maintain a urine pH greater than 7. Usually, sodium bicarbonate solution (50 to 100 mmol/L) is added to intravenous fluids and then adjusted so that an alkaline urine pH is maintained. The carbonic anhydrase inhibitor acetazolamide may be used to increase the effects of alkalinization. It is important to remember that alkalinization is secondary to the overall goal of decreasing urinary uric acid concentration by increasing urine volume.

Allopurinol, a xanthine oxidase inhibitor, is the mainstay of drug treatment and may be started 1 to 2 days before cytotoxic treatment. Dosages range from 300 to 600 mg/d, and therapy is usually continued for 1 to 2 weeks or until the danger of hyperuricemia has passed.

Rasburicase (Elitek) is an antihyperuricemia drug. It has been approved by the FDA for malignancy-associated hyperuricemia in pediatric patients but is also used in adults. The usual pediatric dose is 0.15 or 0.2 mg/kg IV over 30 minutes for 5 days. The usual adult dosage is 0.15 to 0.2 mg/kg/d, based on limited studies.

Acute oliguria

In patients in whom acute oliguria develops, ureteral obstruction by urate calculi should be considered. This condition should be evaluated by ultrasonography or CT. Administration of intravenous contrast agents for pyelography should be avoided, because they may increase the risk of acute tubular necrosis.

Dialysis

Patients with advancing renal insufficiency and subsequent renal failure may benefit from peritoneal dialysis or hemodialysis. Dialysis has been shown to be effective in reversing renal failure caused by urate deposition.