Tartronic Acid as a Potential Inhibitor of Pathological Calcium Oxalate Crystallization

Kidney stones are a pervasive disease with notoriously high recurrence rates that require more effective treatment strategies. Herein, tartronic acid is introduced as an efficient inhibitor of calcium oxalate monohydrate (COM) crystallization, which is the most prevalent constituent of human kidney stones. A combination of in situ experimental techniques and simulations are employed to compare the inhibitory effects of tartronic acid with those of its molecular analogs. Tartronic acid exhibits an affinity for binding to rapidly growing apical surfaces of COM crystals, thus setting it apart from other inhibitors such as citric acid, the current preventative treatment for kidney stones. Bulk crystallization and in situ atomic force microscopy (AFM) measurements confirm the mechanism by which tartronic acid interacts with COM crystal surfaces and inhibits growth. These findings are consistent with in vivo studies that reveal the efficacy of tartronic acid is similar to that of citric acid in mouse models of hyperoxaluria regarding their inhibitory effect on stone formation and alleviating stone-related physical harm. In summary, these findings highlight the potential of tartronic acid as a promising alternative to citric acid for the management of calcium oxalate nephropathies, offering a new option for clinical intervention in cases of kidney stones. This study introduces tartronic acid as a potent inhibitor of calcium oxalate monohydrate (COM) crystallization, pivotal in kidney stone formation, through specific inhibitor-crystal interactions. In vivo experiments demonstrate the efficacy of tartronic acid in inhibiting stone formation and mitigating stone-related harm in hyperoxaluria mouse models. This discovery holds significant promise for advancing the treatment of pathological calcium oxalate crystallization. image