Uric acid is produced in the liver as a byproduct of purine metabolism. Measurement of uric acid is useful in the evaluation of gout and monitoring of certain types of chemotherapy. Uric acid levels are increased in situations with increased dietary purine intake, reduced excretion, or increased production. In addition, volume status affects uric acid secretion. With a decrease in extracellular volume, uric acid excretion declines, and serum uric acid levels increase. Conversely, volume expansion increases uric acid excretion and leads to hypouricemia. Several drugs inhibit the reabsorption of uric acid in the kidney and therefore lead to uricosuria (Table 15-25).
Progressively higher levels of hyperuricemia predict the likelihood of gout; however, most authorities believe that asymptomatic hyperuricemia should not be treated. At 37° C, saturation in plasma occurs when uric acid levels are greater than 6.8 mg/dL. Most patients with gout have uric acid levels greater than 7 mg/dL at some time, but they can have normal serum uric acid levels at the time of an acute gouty attack. Although a biologically significant uric acid level is greater than 6.8 mg/dL, the upper limits of "normal" based on population studies are 7.7 mg/dL for men and 6.8 mg/dL for women. The incidence of gout is approximately 5% per year in men with uric acid levels greater than 9 mg/ dL, but only 0.5% per year with uric acid levels of 7.0 to 8.9 mg/dL.
A distinction between production of uric acid and reduced uric acid excretion as a cause of hyperuricemia may be helpful in evaluating patients with gout. This can be accomplished by measurement of 24-hour urinary uric acid and creatinine excretion. "Underexcretion" is identified when the fractional excretion (excretion of uric acid/ excretion of creatinine) is less than 6%. When a person is consuming a regular diet, excretion of uric acid greater than 800 mg/day is considered hyperuricosuria. Follow-up testing for patients with hyperuricosuria can be repeated on a low-purine diet, with 24-hour excretion of uric acid greater than 600 mg indicating uric acid overproduction. Of patients with gout, an estimated 90% have reduced uric acid excretion, and less than 10% have overproduction of uric acid as the cause. Drugs that lower serum uric acid include losar-tan, amlodipine, fenofibrate, and atorvastatin.
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