Renal handling of uric acid in gout: Impaired tubular transport of urate not dependent on serum urate levels

Abstract

Metabolic studies were conducted in 56 patients with primary gout and in ten normal subjects to assess differences in the tubular transport mechanisms of urate. Renal handling of uric acid was examined by means of pyrazinamide and probenecid tests at increased and pharmacologically reduced serum urate concentrations in both groups. Patients with gout showed similar serum urate levels and glomerular filtration rates than controls at both serum urate levles. Pyrazinamide decreased urinary uric acid excretion to less than 1.0% of the urate filtered load in both groups at increased and diminished serum urate concentrations. The maximum uricosuric response promoted by probenecid at high serum urate levels was (mean ± SD) 3,707 ± 443 μg/min/1.73 m 2 in controls and 2,215 ± 738 μg/min/1.73 m 2 in patients with gout ( P < 0.01). Forty-four patients had a daily uric acid excretion rate below 700 mg/1.73 m 2, and all of them showed a diminished uricosuric response to probenecid. When serum urate was reduced in normal subjects and 30 patients to a mean of 2.1 and 2.3 mg/dL, respectively, probenecid elicited a significantly lower urate excretion rate in gout (532 ± 202 μg/min/1.73 m 2) than in controls (922 ± 136 μg/min/1.73 m 2; P < 0.01). Among these 30 patients examined in their basal state and at decreased serum urate levels, uric acid excretion following probenecid was normal in six and diminished in 24 in both situations. The difference between maximum uricosuria and basal urate excretion was not increased in gouty patients. [2- 14C]uric acid kinetics showed a metabolic clearance rate of 6.3 ± 1.5 L/24 h/m 2 in five gouty normoexcretors and 3.5 ± 0.8 L/24 h/m 2 in three underexcretors ( P < 0.01), classified according to both 24-hour uric acid excretion and the uricosuric response elicited by probenecid. These data suggest an impaired tubular secretion of urate in most patients with gout that is not normalized by decreasing serum urate levels. The impaired tubular transport of urate may contribute to increased serum urate in primary gout.