Deciphering Physicochemical Properties of Urinary Proteins from Stone Formers as Macromolecular Prolithogenic Factors...

A recent study has identified several urinary proteins from calcium oxalate (CaOx) stone formers (patients with CaOx kidney stones) that promote stone development. Nevertheless, the physicochemical properties responsible for their prolithogenic effects remained undefined. In this study, stone formers' urinary proteins were fractionated into 15 fractions (SF1-SF15) using chromatographic methods and analyzed through a series of CaOx crystal assays, followed by protein identification via tandem mass spectrometry. Physicochemical properties of all proteins identified in individual fractions, along with their crystal-promoting activities, were then analyzed and subjected to the Pearson correlation test. The majority of protein fractions exhibited crystal-promoting effects. Crystallization-promoting activity positively correlated with the proportion of oxalate-binding proteins, while aggregation-promoting activity positively correlated with the number of oxalate-binding sites/protein and isoelectric point (pI). Crystal adhesion-promoting activity negatively correlated with the number of oxalate-binding sites/protein, pI, proportion of basic proteins, and proportion of alpha-helix structure but positively correlated with the proportion of acidic proteins and proportion of random-coil structure. None of the physicochemical properties correlated with crystal growth-promoting activity. In conclusion, some physicochemical properties of urinary proteins from stone formers are associated with their CaOx stone-promoting activities and may serve as predictors for their prolithogenic potential.