(659e) Inhibition of Calcium Oxalate Monohydrate Crystallization Using Organic Acids

Inhibition of Calcium Oxalate Monohydrate Crystallization using Organic Acids

Jihae Chung¹, Michael G. Taylor², Isadora Carnaval², Giannis Mpourmpakis², John R. Asplin³, and Jeffrey D. Rimer¹

¹University of Houston, Department of Chemical and Biomolecular Engineering, Houston, TX 77204

²University of Pittsburgh, Department of Chemical and Petroleum Engineering, Pittsburgh, PA 15261

³Litholink Corporation and Renal Section, School of Medicine, University of Chicago, Chicago, IL 60637

Kidney stone disease is one of the most common disorders where the number of people afflicted is on the rise; however, there have been no significant advancements in therapeutic treatments for this disease over the past three decades. More than 80% of human kidney stones are calcium oxalate monohydrate (COM) polycrystalline aggregates. The current therapeutic for COM stones is citrate, an over-the-counter supplement with moderate inhibitory effect on COM crystal growth and relatively low compatibility with patients when consumed for an extended period of time. We have explored the effects of hydroxycitrate (HCA), which is a molecular analogue of citrate that is a more potent inhibitor of COM crystal growth, and is thus a possible replacement of citrate as a therapy. HCA differs from citrate by only one hydroxyl group, yet interestingly, this subtle structural difference leads to completely different modes of interaction with COM crystal surfaces. Here, we will compare the effects of citrate and hydroxycitrate on COM crystallization. Our studies focus on the effects of growth inhibitors at both macroscopic and microscopic length scales. In bulk crystallization assays, we quantified the effect of inhibitors on the bulk crystal habit as well as their impact on the kinetics of crystallization. We employ in situ atomic force microscopy (AFM) to probe the interfacial interactions between inhibitors and COM crystal surfaces in real time. Working in conjunction with collaborators, we are exploring the effects of HCA and other modifiers in vivo and in silico to establish a synergistic platform to rationally design crystal growth inhibitors, which can then be used to develop new drugs for pathological diseases involving mineralization.