(601c) Elucidating the Influence of Hydroxycitrate on Brushite Crystallization Via Bulk and Interfacial Studies

Kidney stone diseases (nephrolithiasis) affect 12% of the world population and can occur on all ages, sexes and races. Of all the cases, calcium stones are the most prevalent and 20% of these are calcium phosphates (CaP). Brushites, or dicalcium phosphate dihydrate, are one of the types of CaP stones and known to induce calcium oxalate mineralization, and to be converted to less soluble form hydroxyapatite. Kidney stone incidence has increased about three times for the past decades. Efforts in identifying alternative inhibitors of stone growth remain one primary strategy in preventing the increasing occurrence of kidney stones. Once identified and obtained clinical clearance, this may provide patients more choices for therapeutics against pathological calcification. Fundamentally, carboxylates are known to inhibit crystal growth of these minerals and one example is hydroxycitrate (HCA) with have effectively curbed calcium oxalate mineralization. To tackle this goal, we employed a combination of bulk and atomic force microscopy studies to elucidate the impact of HCA on the crystal size, morphology, number density of CaP. Analysis shows a 50 % reduction in the number of crystals formed and an increase in the aspect ratio at a very small inhibitor concentration (Ca/inhibitor=25000). Amplitude and Frequency Modulated AFM studies show that surface roughness increased through time in the presence of the HCA. Changes in the periodic features at near atomic resolution was also observed in the presence of HCA implying possible modifier-crystal surface interactions. Results obtained in this study may serve as a step in understanding the inhibitors’ effect on CaP crystals and in designing preventative drugs for kidney stone disease.