Abstract
Recent large 3 cohorts have shown that caffeinated beverage consumption was associated with lower risk of kidney stone disease. However, its protective mechanisms remained unknown and had not been previously investigated. We thus evaluated protective effects of caffeine (1 μM–10 mM) on calcium oxalate monohydrate (COM) kidney stone formation, using crystallization, crystal growth, cell-crystal adhesion, Western blotting, and immunofluorescence assays. The results showed that caffeine reduced crystal number but, on the other hand, increased crystal size, resulting in unchanged crystal mass, consistent with crystal growth that was not affected by caffeine. However, caffeine significantly decreased crystal-binding capacity of MDCK renal tubular cells in a dose-dependent manner. Western blotting and immunofluorescence study of COM crystal-binding proteins revealed significantly decreased level of annexin A1 on apical surface and its translocation into cytoplasm of the caffeine-treated cells, but no significant changes in other COM crystal-binding proteins (annexin A2, α-enolase, HSP70, and HSP90) were observed. Moreover, caffeine decreased intracellular [Ca2+] but increased [Ca2+] secretory index. Taken together, our findings showed an in vitro evidence of the protective mechanism of caffeine against kidney stone formation via translocation of annexin A1 from apical surface into cytoplasm to reduce the crystal-binding capacity of renal tubular epithelial cells.
Highlights
Intake and reduction of kidney stone incidence has been found, protective mechanisms of caffeine against kidney stone disease remained unknown and had not been previously investigated
The first step of Calcium oxalate monohydrate (COM) kidney stone formation is crystallization, which is a transition of calcium and oxalate ions from solubilized liquid phase to the solid phase as crystalline particles
Quantitative data showed that caffeine significantly reduced number of COM crystals, but on the other hand increased the crystal size, independent of its dosage (Fig. 1B and C)
Summary
Intake and reduction of kidney stone incidence has been found, protective mechanisms of caffeine against kidney stone disease remained unknown and had not been previously investigated. The present study aimed to evaluate the protective effects of caffeine on COM kidney stone formation at early phases, including crystallization, crystal growth, and cell-crystal adhesion. Effects of caffeine on expression levels and localizations of known COM crystal-binding proteins (including annexin A1, annexin A2, α-enolase, HSP70 and HSP90) were determined by Western blot analysis and immunofluorescence staining followed by laser-scanning confocal microscopy.
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