Evidence for altered renal urate reabsorption during changes in volume of the extracellular fluid.

作者：Thomas H. Steele · 发表于：PubMed · 年份：1969 · 被引用次数：129 · 研究领域：Gout, Hyperuricemia, Uric Acid、Urological Disorders and Treatments

Abstract Although substrate-regulated tubular secretion contributes the major fraction of the urinary urate, altered reabsorption of filtered urate might also affect urate homeostasis under appropriate conditions. Since changes in the volume of the extracellular fluid may activate a mechanism which alters the reabsorption of several filtered solutes, the possibility of changes in urate reabsorption, during volume expansion and contraction, was investigated through renal clearance studies in man. Urate excretion normally did not increase significantly, either during rapid isotonic saline infusions or after the expansion of the extracellular fluid volume to a standard degree with isotonic saline, until very high excretion rates for sodium occurred. However, after specific inhibition of the urate secretory mechanism by pretreatment with pyrazinamide (PZA), both the excretion and estimated fractional excretion of urate increased significantly during saline infusion. When acute extracellular fluid volume depletion was induced by ethacrynic acid diuresis in subjects pretreated with pyrazinamide, urate excretion and estimated fractional excretion fell to low levels. This decrease did not occur when volume depletion was prevented by the replacement of urinary losses with saline after diuretic administration. The data suggest that renal urate reabsorption is a flexible parameter, with altered transport activity during extracellular fluid volume expansion or contraction. Since reabsorp...