The renal mechanism for urate homeostasis in normal man

Abstract

In thirty-two studies on ten normal subjects, renal urate secretion and reabsorption have been estimated by noting the decrement in UV urate: C inulin produced by a maximally effective dose of pyrazinamide (TS ur), a drug which markedly although probably not completely inhibits tubular urate secretion. In each subject studies were performed in the control state, after decreasing plasma urate with allopurinol, and following elevation of plasma urate levels by RNA loading. Urate reabsorption remained at an average of 98 per cent of filtered load at all plasma levels, thereby indicating progressive augmentation of reabsorptive transport velocity with increasing filtered loads. Also, tubular secretion per nephron was a direct function of plasma urate concentration. Although plasma urate levels ranged as high as 12.8 mg. per 100 ml., at no time was there evidence for attainment of a secretory or reabsorptive tubular transport maximum. A provisional normal standard was set forth, relating TS ur to plasma urate concentration through a regression treatment with appropriate confidence limits. These data suggest that normal man displays an augmented rate of bidirectional urate transport with increasing substrate availability. Due to the nature of this bidirectional transport system, an increase in secretory rate serves to increase net urate excretion and thereby provides the homeostatic mechanism which tends to minimize the hyperuricemic response to an increase in uric acid synthesis. The pyrazinamide suppression technic appears to provide a means of assessing the integrity of this homeostatic mechanism within the residual nephrons of the chronically diseased kidney or in patients who have gout.