Comparison of Calcium Oxalate Stone Matrix Proteomics Data to Predictions from In Vitro Studies of Protein–Crystal Interactions

Calcium oxalate kidney stones are organic–inorganic composites that form spontaneously in the urine of many mammals, causing significant disease in humans. Known treatments have limited effectiveness and are based solely on control of the small ion chemistry of patients’ urine. The organic matrix binding crystals together contains a complex mixture of predominantly urine proteins, though the role of proteins in kidney stone formation is poorly understood. Fundamental studies of protein/polymer interactions with calcium oxalate crystallization processes (i.e., nucleation, growth, aggregation, and cell binding), including significant contributions from Michael Ward’s laboratory, have highlighted specific chemical and structural features of proteins that would support stone formation. This review compares recent detailed calcium oxalate stone matrix proteomics results to results from model polymer/protein studies, finding evidence that the matrix protein distributions illustrate principles identified in fundamental studies of protein crystal interactions. These results support the key principles of our model that protein–crystal surface interactions driven by strongly anionic proteins combine with protein–protein interactions, driven partially by charge interactions, to create kidney stones.