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Abstract: SA-PO216

Comparison of Cat to Human Calcium Oxalate Monohydrate Kidney Stone Matrix Proteomes

Session Information

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic

Author

  • Wesson, Jeffrey, Department of Veterans Affairs, Milwaukee, Wisconsin, United States
Background

Despite its critical nature, the role of matrix in calcium oxalate stone formation is poorly understood. The wide diversity of proteins comprising matrix has contributed to the ambiguity. Because cats share many clinical characteristics of their stone disease with humans, we have compared the protein distributions measured by mass spectrometry in human calcium oxalate stone matrix to that observed in cat stone matrix.

Methods

Raw data from previously published proteomic studies of human urine and calcium oxalate monohydrate stone matrix were acquired and re-analyzed with similarly acquired proteomic data for calcium oxalate moinohydrate stones obtained from cats. All data were analyzed using in house developed algorithms at the Mayo Clinic Proteomic Facility using the human or cat protein databases as appropriate. The observed protein distributions were analyzed in the context of a recent model of stone formation based on the aggregation of strongly anionic and strongly cationic proteins which includes selective adsorption of other proteins based on total charge.

Results

Matrix protein distributions shared many common features between humans and cats, including enrichment of both strongly anionic and strongly cationic proteins, increased total charge in matrix proteins compared to urine proteins, and a high degree of similarity of prominent strongly anionic proteins in the matrix of both species. However, there was weaker overlap of the specific dominant proteins in other regions of the net charge distribution.

Conclusion

Collectively, these observations support the conceptual model where the strongly anionic proteins associate most strongly with the calcium oxalate crystal surfaces, while the other proteins associate with the strongly anionic proteins through nonspecific, charge interactions with each other to create stones. Also, cats appear to be the best animal model of human stone disease identified to date based on these similarities.

Funding

  • Veterans Affairs Support