Renal excretion of hypoxanthine and xanthine in primary gout

Abstract

The renal excretion of uric acid is usually diminished in primary gout with respect to increased serum urate levels. To determine whether the renal excretion of uric acid precursors, hypoxanthine and xanthine, is also abnormal in primary gout, the concentrations of these purines were measured in plasma and 24-hour urine samples in normal subjects, in patients with primary gout and uric acid underexcretion, and in patients with enzyme deficiencies that are known to result in over-production of uric acid. Three groups of subjects were studied: Group I consisted of 10 ambulatory healthy normal men; Group II consisted of 15 patients in whom primary gout was diagnosed; and Group III consisted of 10 patients with various enzyme defects known to produce an excessive synthesis of uric acid. In each subject, plasma and 24-hour urinary uric acid, hypoxanthine, xanthine, and creatinine concentrations were measured and the mean of three consecutive determinations was used. The fractional excretion of purine compounds was calculated from a formula. Hypoxanthine phosphoribosyltransferase, adenine phosphoribosyltransferase, and hemoglobin were also measured in each subject. Plasma hypoxanthine and xanthine were increased in the two groups of patients compared with the control subjects. Urinary hypoxanthine and xanthine levels were reduced in gouty patients compared with control subjects, whereas levels were increased in patients with uric acid overproduction. A positive correlation was found between the renal clearances of uric acid, hypoxanthine, and xanthine. The results indicate that the renal excretion of hypoxanthine and xanthine is severely impaired in most patients with primary gout.