Use of pyrazinamide to assess renal uric acid transport in the rat: a micropuncture study

Abstract

Free-flow micropuncture studies were performed to evaluate renal uric acid transport in control and pyrazinamide-treated rats. In all studies [2-14C]uric acid and [methoxy-3H]inulin were administered. [2-14C]uric acid was determined after column chromatographic separation from its labeled oxidation product in tubular fluid, plasma, and urine. Tubular fluid collections were obtained from the early and late proximal tubule under hydropenic conditions and from the early proximal tubule during volume expansion induced with 0.9% sodium chloride. These studies indicate that pyrazinamide, in the dose employed, provokes a uniform reduction in fractional uric acid excretion but simultaneously inhibits both net uric acid reabsorption and secretion in the early and late proximal tubule, respectively. In addition, these experiments unmasked uric acid reabsorption within the late proximal tubule and bidirectional transport beyond this nephron site. These studies also suggest at least two mechanisms for uric acid reabsorption; one sodium dependent, the other independent of sodium and water transport.