Urate and calcium oxalate stones: from repute to rhetoric to reality

A critical appraisal of the evidence commonly cited to support a link between high urate excretion and calcium oxalate (CaOx) urinary calculi is presented. Two theories have been invoked to provide a scientific explanation for urate's apparent promotory effect. The first proposes that urinary urate crystals promote CaOx precipitation by the phenomenon of epitaxy; the second hypothesis is that colloidal particles of urate reduce the inhibitory activity of urinary glycosaminoglycans (GAGs) which normally prevent the crystallization of CaOx. However, to the present, neither has been verified experimentally. More recent research from our group has revealed that at normal physiological pH values dissolved urate directly promotes CaOx precipitation by the classic 'salting-out' effect by enhancing nucleation, growth and aggregation of CaOx crystals. It is therefore suggested that the beneficial effect of allopurinol in reducing CaOx stone recurrences may be attributed to its lowering the urinary output of urate and thereby reducing the probability that CaOx will be salted out of urine, rather than to epitaxy or inactivation of urinary GAGs.