Uric acid metabolism in normal subjects and in gouty patients by chromatographic measurement of ¹⁴C-uric acid in plasma and urine

Abstract

The turnover kinetics of uric acid were determined in a group of 25 subjects, including 6 controls, 17 gouty patients, and 2 subjects with asymptomatic hyperuricemia. According to their daily urate excretion while on a purine-free diet, the gouty patients (none of whom had evidence of tophi at the time of the study) were classified as follows: five overexcretor patients (“metabolic” gout), six normo-excretor patients (“renal” gout), and six borderline patients. Uric acid-2-¹⁴C was used as the tracer, and the uric acid radioactivity in plasma and urine samples was measured after column chromatography through a polyacrylamide gel that specifically adsorbs uric acid. The experimental data of plasma disappearance curves and urine radioactivities of ¹⁴C-uric acid (followed up to 3 days after injection) were analyzed by the noncompartmental approach and by the urine/plasma ratio method, in order to calculate the total removal rate of uric acid, its distribution volumes, and the removal rate of uric acid through the renal route. The monocompartmental approach and the urine specific radioactivity methods were also employed to compute the uric acid turnover data, and the results were compared with those of noncompartmental analysis. The overexcretor patients were found to have normal metabolic clearance rate and fractional catabolic rate values, but significantly higher-than-normal total turnover rate values (p < 0.005), whereas the normo-excretors had normal total turnover rate values but significantly lower metabolic clearance rate and fractional catabolic rate values compared to the controls (p < 0.001). Uric acid excretion through the kidneys was found to be about two-thirds of the total removal both in the control subjects and in the gouty patients. The results obtained allowed the exclusion of any significant delay in the excretion of uric acid through the kidneys. The use of monocompartmental analysis led to a significant overestimation of both the total turnover rate (p < 0.005) and the total pool of uric acid (p < 0.001), and the urine specific radioactivity approach implied a significant overestimation of the total turnover rate (p < 0.001). The gouty patients as a whole had a significantly larger-than-normal (p < 0.001) total pool of uric acid, however determined. On the basis of the results obtained, a metabolic differentiation was made possible for the two pathophysiologic types of gout. In fact, the metabolic gout patients were all characterized by normal metabolic clearance rate values and increased total pool values, whereas the renal gout patients were all characterized by reduced metabolic clearance rate values and increased total pool values.