Possible Function of Urinary pH and Citrate on the Ceftriaxone-induced Nephrolithiasis

Objective To test whether urinary pH and citrate is associated with ceftriaxone-induced kidney stone formation and if acidified urine could dissolve this kind of stone using an in vitro crystallization model. Methods Crystallization was induced by mixing ceftriaxone at the standard therapeutic urinary concentration to artificial urine. The response of different physiological pH and citrate on ceftriaxone-induced crystallization was measured by the depletion ratio of ceftriaxone in the process. Compositions of formed crystals were qualitatively and quantitatively analyzed. The effect of acidifying urine on dissolving of ceftriaxone-induced crystal was determined by the surplus ratio of ceftriaxone in the process. Results Compositional analysis showed that ceftriaxone-induced crystals were composed of calcium and ceftriaxone with a ratio of 1:1. Compared to the response to pH 6.0, ceftriaxone-induced crystallizations in artificial urine at pH 4.5 and 5.0 for 4 hours were significantly decreased, and more acid urine resulted in less crystallization. However, it made no significant change when pH increased to 6.5 and 7.0. In addition, ceftriaxone-induced crystals formed at pH 6.0 for 4 hours could be dissolved significantly when artificial urine was acidified to pH 5.0 and 4.5 for 1, 2, and 4 hours; and more time of dissolution and more degree of acidifying resulted in more dissolution. Conclusion Our study suggests that urinary pH and citrate are probable factors associated with ceftriaxone-induced nephrolithiasis. On one hand, alkaline urine and hypocitraturia predispose ceftriaxone nephrolithiasis, and vice versa. On the other hand, acidifying urine could dissolve ceftriaxone-induced stones.