Abstract
Urine pH has been thought to be an important factor that can modulate kidney stone formation. Nevertheless, there was no systematic evaluation of such pH effect. Our present study thus addressed effects of differential urine pH (4.0–8.0) on calcium oxalate (CaOx) crystallization, crystal-cell adhesion, crystal internalization into renal tubular cells, and binding of apical membrane proteins to the crystals. Microscopic examination revealed that CaOx monohydrate (COM), the pathogenic form, was crystallized with greatest size, number and total mass at pH 4.0 and least crystallized at pH 8.0, whereas COD was crystallized with the vice versa order. Fourier-transform infrared (FT-IR) spectroscopy confirmed such morphological study. Crystal-cell adhesion assay showed the greatest degree of crystal-cell adhesion at the most acidic pH and least at the most basic pH. Crystal internalization assay using fluorescein isothiocyanate (FITC)-labelled crystals and flow cytometry demonstrated that crystal internalization into renal tubular cells was maximal at the neutral pH (7.0). Finally, there were no significant differences in binding capacity of the crystals to apical membrane proteins at different pH. We concluded that the acidic urine pH may promote CaOx kidney stone formation, whereas the basic urine pH (i.e. by alkalinization) may help to prevent CaOx kidney stone disease.
Highlights
Urine compositions can be used to evaluate the stone risk and to monitor therapeutic response in patients with nephrolithiasis/urolithiasis[1, 2]
Several previous studies have shown that calcium oxalate (CaOx) crystals can form inside distal renal tubules and urine pH is a crucial factor affecting such crystallization[24,25,26,27]
We evaluated the effect of differential pH on CaOx crystallization in artificial urine (AU)
Summary
Urine compositions can be used to evaluate the stone risk and to monitor therapeutic response in patients with nephrolithiasis/urolithiasis[1, 2]. Several stone types, including calcium oxalate (CaOx), calcium phosphate, uric acid, etc., have been reported to be modifiable by urine pH1, 8, 12. The most common hydrate form of CaOx crystals found inside the stone matrix is CaOx monohydrate (COM or whewellite), whereas CaOx dihydrate (COD or weddellite) is the second[17] Between these two forms, COM is more pathogenic, whereas COD is more physiologic, as the latter can be found in the urine of healthy individuals when it is concentrated but the former or pathogenic form is usually found in the urine of the stone formers[18,19,20]. Urine pH has been well recognized as one of the modulators for kidney stone formation, there was no systematic evaluation of such pH effects In this present study, we examined effects of www.nature.com/scientificreports/. Differential urine pH (from 4.0 to 8.0) on CaOx crystallization, crystal-cell adhesion, crystal internalization into renal tubular cells, and binding of apical membrane proteins to the crystals
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