INCREASING EXCRETION OF URATE WITH DISPLACING AGENTS IN MAN*

Abstract

A normal healthy adult on a low purine and restricted protein intake produces approximately 700 mg of urate per day.Of this total, 200 mg (30% ) may be eliminated by secretion into the intestinal tract and subsequent breakdown by the gut microorganisms.'The other 500 mg must be eliminated via the kidneys, a process stimulated by uricosuric drugs.2Because the bulk of this urate is formed by extrarenal purine oxidation, it must be transported via the plasma to the kidney. ALBUMIN BINDING AND RENAL DISPOSITION OF URATE IONSBy various techniques, it has been shown that the mate anion will bind to various plasma proteins,3-?although there is considerable controversy about the degree to which such binding may occur in vivo at 37" C (see TABLE 1).The consensus is that the bulk (i.e., 70% or more) of the total urate bound to human plasma is associated with the albumin fraction, because 5 % albumin solutions in hypotonic or isotonic media will bind urate to approximately the same degree as whole (heparinized) plasma.It is clear that urate binding to either whole plasma or the homologous albumin is less extensive at 37" C than at lower temperatures and may vary considerably between different animal species.'Within one species, the extent of binding also depends upon whether the urate ion is added to the plasma as uric acid (pK, 5.4) or the relatively soluble lithium salt, with the possibility that the lithium ion acts as a ligand to promote protein binding.'The literature contains some dogmatic statements that urate binding to albumin in man is of little physiological significance.However, some of these statements cannot be accepted because several artifacts t that may have biased the experimental data from which these negative conclusions were drawn.In our own experiments, which employ either equilibrium dialysis or ultrafiltration, we have consistently found that