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Urinary proteins from stone formers/patients have been hypothesized to promote the formation of kidney stones, but with unclear information. In this study, urinary proteins derived from patients with calcium oxalate (CaOx) kidney stones were fractionated based on their isoelectric points using fast protein liquid chromatography with a GigaCap Q-650M column. Individual protein fractions were then purified and examined by multiple CaOx crystal assays, which simulate the stone-forming events, and identified by tandem mass spectrometry. Their physicochemical properties were then analyzed to find their correlations with the crystal-promoting activities. From all 9 fractions (SFQ1 to SFQ9), almost all of them promoted CaOx crystallization, growth, aggregation, and crystal-cell adhesion, and 10, 12, 71, 71, 60, 55, 25, 38, and 6 were identified from SFQ1 to SFQ9, respectively. Among several abundance-weighted physicochemical parameters, molecular weight, instability index, amino acid composition, and secondary structure positively correlated with abundance-weighted crystal aggregation-promoting activity and crystal adhesion-promoting activity. The findings elucidated the roles of urinary proteins from stone formers in kidney stone promotion, contributing to a better understanding of disease mechanisms.
Suttapitugsakul et al. (Sun,) studied this question.