FACTORS AFFECTING URATE EXCRETION FOLLOWING DIURETIC ADMINISTRATION IN MAN

In order to investigate the mechanism of diuretic-induced urate retention and hyperuricemia, renal clearance studies were performed in normal subjects, utilizing furosemide and ethacrynic acid. After the intravenous administration of either diuretic, uric acid excretion always increased, at least transiently. However, during the second hour following furosemide or ethacrynic acid, uric acid excretion decreased during diuretic-induced extracellular fluid volume contraction, but remained near or above control levels when urinary losses were simultaneously replaced with isotonic saline solution. The extremely low rates of uric acid excretion in the volume-depleted subjects suggested that tubular secretion was impaired. Since the diminution in uric acid excretion occurred only after volume depletion, a direct effect of these diuretics on tubular secretion is unlikely. Instead, it is postulated that stimulatory and suppressive effects of furosemide and ethacrynic acid on urate secretion could be mediated indirectly through altered renal blood flow and angiotensin release, respectively. © 1969.