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

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 levels. 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 micrograms/min/1.73 m2 in controls and 2,215 +/- 738 micrograms/min/1.73 m2 in patients with gout (P less than 0.01). Forty-four patients had a daily uric acid excretion rate below 700 mg/1.73 m2, 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 micrograms/min/1.73 m2) than in controls (922 +/- 136 micrograms/min/1.73 m2; P less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)