The Relationship Between Citrate and Calcium-Oxalate Crystal Agglomeration

Abstract

Hypocitraturia has been recognized as a frequent biochemical abnormality in patients with nephrolithiasis. Several clinical studies have demonstrated the beneficial effects of alkali administration in renal stone prevention in hypocitraturic patients (1). The mechanism, however, by which hypocitraturia promotes renal stone formation has not yet been identified. It is generally assumed that low citrate concentrations increase the saturation of urine with calcium oxalate, as citrate is known to form soluble complexes with calcium. This explanation fails to recognize the fact that stone formation is a complex process which encompasses two major physicochemical components, thermodynamics and kinetics. The first includes the supersaturation which results in nucleation, while the second comprises the rates of nucleation, of crystal growth, and of crystal agglomeration. There are numerous published data in support of the importance of this distinction. They range from the finding of the same degree of crystalluria in healthy subjects and in stone formers to the observation that renal stones have typically an agglomerate structure. Research efforts have mainly concentrated on the analysis of the thermodynamically-regulated processes since investigation of the kinetic processes has been hampered by methodological difficulties. Attempts to analyze the kinetic component have produced conflicting results. The reason for this is that the methods used assessed mainly the effects of promoters or inhibitors of crystallization on crystal growth and agglomeration combined. These two processes, however, are not necessarily linked to each other and can even be oppositely affected by different compounds (2, 3).