Renal excretion of urate: Factors determining the actions of drugs

Our assignment is to cover the literature on urate excretion as studied by microtechniques, the related studies on drugs, and sufficient other literature to put the foregoing in context. In addition, we have been asked to comment on certain technical problems attending studies of urate transport in individual nephrons. Space will not permit systematic consideration of the various drugs known to alter the renal disposition of urate in one or more species. Instead, we will concentrate on the physiologic factors of urate excretion that determine the direction and extent of drug action. Much of the literature on individual drugs has been summarized in recent reviews [1-4].A large fraction of the interesting observations on urate excretion have been made in studies on humans. Some of the interpretations of these phenomena were based on observations made in other animals. For example, observe the use of comparative physiology in the Gutman and Yü exposition of the three-component mechanism for urate excretion [5]. Later, attempts were made to verify the hypotheses developed for the human kidney by studies in animals with a variety of techniques including mi-cropuncture, in vivo microperfusion, in vitro microperfusion, tubular microinjection, and capillary microperfusion. These studies and others using more conventional techniques are producing a pattern of great complexity in the comparative physiology of urate excretion and, to our surprise, of organic anion transport in general. This complexity may be viewed either as offering a variety of opportunities for finding particular models of the phenomena observed in humans or as a variety of traps leading to spurious interpretations of human physiology. Both views have merit