Observations upon calcium oxalate crystallization kinetics in simulated urine

Abstract

Two major etiologic theories of urinary stones are excessive saturation of urine with crystallizable substances or defects in inhibitors that allow relative supersaturation to occur. To date, it has been difficult to confirm the supersaturation theory in experiments using diffusion-limited crystallization systems because direct measurements of the nucleation process of crystallization could not be performed. We used well developed, continuous crystallizer techniques and adapted them from industrial use to the study of stone disease. Data derived from the experiments allow the absolute measurement of crystal growth rate and determination of nucleation rate. These methods were applied to study the calcium oxalate dihydrate (weddellite) system in artificial urine that lacked only proteinaceous components. Based on these experiments it was not possible to grow crystals large enough within 5 to 20 minutes to obstruct the collecting ducts of the kidney. Therefore, it appears that other processes, such as aggregation or stasis within tissues, may well be related to initiation of stone disease. Under the experimental conditions of this study nucleation rate exceeded growth rate. Therefore, multiple small particles are created at the expense of allowing larger particles to grow. Inhibitors can be tested rapidly in this system by adding them in concentrations compatible with those found in urine.