Small-Molecular-Weight Inhibitors

Abstract

The potential role of inhibitors in calcium stone formation is not trivial: it may account for the fact that stones do not occur in the presence of significant urinary supersaturation. Furthermore, if stone formation could be attributed to a lack or deficiency of inhibitors, then their supplementation in the urine could form the basis of preventive therapy. Thus, numerous studies have been undertaken with the object of defining the role of inhibitors in urinary stone disease. These have included investigations of the mechanisms by which they inhibit crystallization in vitro, their excretion characteristics in stone formers and normal controls, and their influence on stone formation in vivo. For the sake of brevity, this review will be confined to a discussion of studies on calcium oxalate (CaOx), although it should be noted that much of the information known about the effects of small-molecular-weight inhibitors on the crystallization of this salt is also available for hydroxyapatite. Further, in summarizing the effects of these inhibitors on CaOx crystallization, I will distinguish between the separate phenomena of nucleation, growth (expressed in most cases as the amount of crystalline material deposited), and aggregation, since it is recognized that each of these may be separately affected by any one inhibitor. Nonetheless, it must be borne in mind that quite apart from any direct influence that an inhibitor may have on any one of these processes, by affecting only one of them, it may unavoidably influence another. For example, Fig. 1 shows the indirect effect that inhibition of just crystal aggregation may have on the amount of crystalline material deposited when crystal growth itself is not directly inhibited. The practical consequences of this will be illustrated later with regard to the inhibitory effect of magnesium.