IMPAIRMENT OF URIC ACID EXCRETION IN GOUT*

Abstract

The renal excretion and clearance of uric acid were determined in 10 nongouty subjects and 11 patients with primary gout before and during an intravenous infusion of lithium urate. Under control conditions prior to the infusion, the mean rate of uric acid excretion was somewhat greater and the mean urate/inulin clearance ratio was somewhat less in gouty than in nongouty subjects, but the renal clearance of urate did not differ significantly in the 2 groups. Under conditions of intravenous urate loading, however, an impairment in uric acid excretion was clearly evident in patients with gout. At equivalent plasma levels and filtered loads, the excretion and clearance of urate and the urate/inulin clearance ratio were significantly less in all of the patients with gout, with one possible exception, than in nongouty control subjects. The demonstration of this functional alteration with such regularity suggested that impaired urate excretion is a characteristic feature of primary gout. In both gouty and nongouty subjects, the differences between the rates of filtration and excretion of urate during intravenous loading were indicative of net tubular reabsorption of this substance. However, net reabsorption was greater in patients with gout than in nongouty subjects at equivalent filtered loads, and with one exception, was not maximally limited with increasing loads. In contrast, a maximal net reabsorptive rate was demonstrated in five of the nongouty subjects studied. On the basis of in vitro studies of urate diffusion, plasma binding was excluded as a cause of reduced urate excretion in patients with gout. Impairment of excretion was therefore attributed to an alteration in renal mechanisms. Whether this alteration involved augmented tubular reabsorption of urate or impairment of tubular secretion was not established.